Skip to main content
Top
Published in: Journal of Translational Medicine 1/2017

Open Access 01-12-2017 | Review

p53: key conductor of all anti-acne therapies

Author: Bodo C. Melnik

Published in: Journal of Translational Medicine | Issue 1/2017

Login to get access

Abstract

This review based on translational research predicts that the transcription factor p53 is the key effector of all anti-acne therapies. All-trans retinoic acid (ATRA) and isotretinoin (13-cis retinoic acid) enhance p53 expression. Tetracyclines and macrolides via inhibiting p450 enzymes attenuate ATRA degradation, thereby increase p53. Benzoyl peroxide and hydrogen peroxide elicit oxidative stress, which upregulates p53. Azelaic acid leads to mitochondrial damage associated with increased release of reactive oxygen species inducing p53. p53 inhibits the expression of androgen receptor and IGF-1 receptor, and induces the expression of IGF binding protein 3. p53 induces FoxO1, FoxO3, p21 and sestrin 1, sestrin 2, and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), the key inducer of isotretinoin-mediated sebocyte apoptosis explaining isotretinoin’s sebum-suppressive effect. Anti-androgens attenuate the expression of miRNA-125b, a key negative regulator of p53. It can thus be concluded that all anti-acne therapies have a common mode of action, i.e., upregulation of the guardian of the genome p53. Immortalized p53-inactivated sebocyte cultures are unfortunate models for studying acne pathogenesis and treatment.
Literature
2.
go back to reference Moradi Tuchayi S, Makrantonaki E, Ganceviciene R, Dessinioti C, Feldman SR, Zouboulis CC. Acne vulgaris. Nat Rev Dis Primers. 2015;1:15029.PubMedCrossRef Moradi Tuchayi S, Makrantonaki E, Ganceviciene R, Dessinioti C, Feldman SR, Zouboulis CC. Acne vulgaris. Nat Rev Dis Primers. 2015;1:15029.PubMedCrossRef
3.
go back to reference Fischer H, Fumicz J, Rossiter H, Napirei M, Buchberger M, Tschachler E, et al. Holocrine secretion of sebum is a unique DNase2-dependent mode of programmed cell death. J Invest Dermatol. 2017;137:587–94.PubMedCrossRef Fischer H, Fumicz J, Rossiter H, Napirei M, Buchberger M, Tschachler E, et al. Holocrine secretion of sebum is a unique DNase2-dependent mode of programmed cell death. J Invest Dermatol. 2017;137:587–94.PubMedCrossRef
4.
go back to reference Cappel M, Mauger D, Thiboutot D. Correlation between serum levels of insulin-like growth factor 1, dehydroepiandrosterone sulfate, and dihydrotestosterone and acne lesion counts in adult women. Arch Dermatol. 2005;141:333–8.PubMedCrossRef Cappel M, Mauger D, Thiboutot D. Correlation between serum levels of insulin-like growth factor 1, dehydroepiandrosterone sulfate, and dihydrotestosterone and acne lesion counts in adult women. Arch Dermatol. 2005;141:333–8.PubMedCrossRef
5.
go back to reference Vora S, Ovhal A, Jerajani H, Nair N, Chakrabortty A. Correlation of facial sebum to serum insulin-like growth factor-1 in patients with acne. Br J Dermatol. 2008;159:990–1.PubMedCrossRef Vora S, Ovhal A, Jerajani H, Nair N, Chakrabortty A. Correlation of facial sebum to serum insulin-like growth factor-1 in patients with acne. Br J Dermatol. 2008;159:990–1.PubMedCrossRef
6.
go back to reference Melnik BC, Schmitz G. Role of insulin, insulin-like growth factor-1, hyperglycaemic food and milk consumption in the pathogenesis of acne vulgaris. Exp Dermatol. 2009;18:833–41.PubMedCrossRef Melnik BC, Schmitz G. Role of insulin, insulin-like growth factor-1, hyperglycaemic food and milk consumption in the pathogenesis of acne vulgaris. Exp Dermatol. 2009;18:833–41.PubMedCrossRef
7.
go back to reference Seleit I, Bakry OA, Abdou AG, Hashim A. Body mass index, selected dietary factors, and acne severity: are they related to in situ expression of insulin- like growth factor-1? Anal Quant Cytopathol Histpathol. 2014;36:267–78.PubMed Seleit I, Bakry OA, Abdou AG, Hashim A. Body mass index, selected dietary factors, and acne severity: are they related to in situ expression of insulin- like growth factor-1? Anal Quant Cytopathol Histpathol. 2014;36:267–78.PubMed
9.
go back to reference Mirdamadi Y, Thielitz A, Wiede A, Goihl A, Papakonstantinou E, Hartig R, et al. Insulin and insulin-like growth factor-1 can modulate the phosphoinositide- 3-kinase/Akt/FoxO1 pathway in SZ95 sebocytes in vitro. Mol Cell Endocrinol. 2015;415:32–44.PubMedCrossRef Mirdamadi Y, Thielitz A, Wiede A, Goihl A, Papakonstantinou E, Hartig R, et al. Insulin and insulin-like growth factor-1 can modulate the phosphoinositide- 3-kinase/Akt/FoxO1 pathway in SZ95 sebocytes in vitro. Mol Cell Endocrinol. 2015;415:32–44.PubMedCrossRef
10.
go back to reference Agamia NF, Abdallah DM, Sorour O, Mourad B, Younan DN. Skin expression of mammalian target of rapamycin and forkhead box transcription factor O1, and serum insulin-like growth factor-1 in patients with acne vulgaris and their relationship with diet. Br J Dermatol. 2016;174:1299–307.PubMedCrossRef Agamia NF, Abdallah DM, Sorour O, Mourad B, Younan DN. Skin expression of mammalian target of rapamycin and forkhead box transcription factor O1, and serum insulin-like growth factor-1 in patients with acne vulgaris and their relationship with diet. Br J Dermatol. 2016;174:1299–307.PubMedCrossRef
11.
go back to reference Tsitsipatis D, Klotz LO, Steinbrenner H. Multifaceted functions of the forkhead box transcription factors FoxO1 and FoxO3 in skin. Biochim Biophys Acta. 2017;1861:1057–64.PubMedCrossRef Tsitsipatis D, Klotz LO, Steinbrenner H. Multifaceted functions of the forkhead box transcription factors FoxO1 and FoxO3 in skin. Biochim Biophys Acta. 2017;1861:1057–64.PubMedCrossRef
12.
go back to reference Gross DN, van den Heuvel AP, Birnbaum MJ. The role of FoxO in the regulation of metabolism. Oncogene. 2008;27:2320–36.PubMedCrossRef Gross DN, van den Heuvel AP, Birnbaum MJ. The role of FoxO in the regulation of metabolism. Oncogene. 2008;27:2320–36.PubMedCrossRef
13.
go back to reference Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell. 2017;168:960–76.PubMedCrossRef Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell. 2017;168:960–76.PubMedCrossRef
14.
go back to reference Ben-Sahra I, Manning BD. mTORC1 signaling and the metabolic control of cell growth. Curr Opin Cell Biol. 2017;45:72–82.PubMedCrossRef Ben-Sahra I, Manning BD. mTORC1 signaling and the metabolic control of cell growth. Curr Opin Cell Biol. 2017;45:72–82.PubMedCrossRef
16.
17.
go back to reference Monfrecola G, Lembo S, Caiazzo G, De Vita V, Di Caprio R, Balato A, et al. Mechanistic target of rapamycin (mTOR) expression is increased in acne patients’ skin. Exp Dermatol. 2016;25:153–5.PubMedCrossRef Monfrecola G, Lembo S, Caiazzo G, De Vita V, Di Caprio R, Balato A, et al. Mechanistic target of rapamycin (mTOR) expression is increased in acne patients’ skin. Exp Dermatol. 2016;25:153–5.PubMedCrossRef
18.
go back to reference Smith TM, Cong Z, Gilliland KL, Clawson GA, Thiboutot DM. Insulin-like growth factor-1 induces lipid production in human SEB-1 sebocytes via sterol response element-binding protein-1. J Invest Dermatol. 2006;126:1226–32.PubMedCrossRef Smith TM, Cong Z, Gilliland KL, Clawson GA, Thiboutot DM. Insulin-like growth factor-1 induces lipid production in human SEB-1 sebocytes via sterol response element-binding protein-1. J Invest Dermatol. 2006;126:1226–32.PubMedCrossRef
19.
go back to reference Smith TM, Gilliland K, Clawson GA, Thiboutot D. IGF-1 induces SREBP-1 expression and lipogenesis in SEB-1 sebocytes via activation of the phosphoinositide 3-kinase/Akt pathway. J Invest Dermatol. 2008;128:1286–93.PubMedCrossRef Smith TM, Gilliland K, Clawson GA, Thiboutot D. IGF-1 induces SREBP-1 expression and lipogenesis in SEB-1 sebocytes via activation of the phosphoinositide 3-kinase/Akt pathway. J Invest Dermatol. 2008;128:1286–93.PubMedCrossRef
21.
go back to reference Zouboulis CC, Jourdan E, Picardo M. Acne is an inflammatory disease and alterations of sebum composition initiate acne lesions. J Eur Acad Dermatol Venereol. 2014;28:527–32.PubMedCrossRef Zouboulis CC, Jourdan E, Picardo M. Acne is an inflammatory disease and alterations of sebum composition initiate acne lesions. J Eur Acad Dermatol Venereol. 2014;28:527–32.PubMedCrossRef
23.
go back to reference Melnik BC. Acne vulgaris: an inflammasomopathy of the sebaceous follicle induced by deviated FoxO1/mTORC1 signalling. Br J Dermatol. 2016;174:1186–8.PubMedCrossRef Melnik BC. Acne vulgaris: an inflammasomopathy of the sebaceous follicle induced by deviated FoxO1/mTORC1 signalling. Br J Dermatol. 2016;174:1186–8.PubMedCrossRef
24.
go back to reference Roca H, Varsos ZS, Pienta KJ. CCL2 is a negative regulator of AMP- activated protein kinase to sustain mTOR complex-1 activation, survivin expression, and cell survival in human prostate cancer PC3 cells. Neoplasia. 2009;11:1309–17.PubMedPubMedCentralCrossRef Roca H, Varsos ZS, Pienta KJ. CCL2 is a negative regulator of AMP- activated protein kinase to sustain mTOR complex-1 activation, survivin expression, and cell survival in human prostate cancer PC3 cells. Neoplasia. 2009;11:1309–17.PubMedPubMedCentralCrossRef
25.
go back to reference Song K, Shankar E, Yang J, Bane KL, Wahdan-Alaswad R, Danielpour D. Critical role of a survivin/TGF-β/mTORC1 axis in IGF-I-mediated growth of prostate epithelial cells. PLoS ONE. 2013;8:e61896.PubMedPubMedCentralCrossRef Song K, Shankar E, Yang J, Bane KL, Wahdan-Alaswad R, Danielpour D. Critical role of a survivin/TGF-β/mTORC1 axis in IGF-I-mediated growth of prostate epithelial cells. PLoS ONE. 2013;8:e61896.PubMedPubMedCentralCrossRef
26.
go back to reference Assaf HA, Abdel-Maged WM, Elsadek BE, Hassan MH, Adly MA, Ali SA. Survivin as a novel biomarker in the pathogenesis of acne vulgaris and its correlation to insulin-like growth factor-I. Dis Markers. 2016;2016:7040312.PubMedPubMedCentralCrossRef Assaf HA, Abdel-Maged WM, Elsadek BE, Hassan MH, Adly MA, Ali SA. Survivin as a novel biomarker in the pathogenesis of acne vulgaris and its correlation to insulin-like growth factor-I. Dis Markers. 2016;2016:7040312.PubMedPubMedCentralCrossRef
27.
go back to reference Melnik BC. Diet in acne: further evidence for the role of nutrient signalling in acne pathogenesis. Acta Derm Venereol. 2012;92:228–31.PubMedCrossRef Melnik BC. Diet in acne: further evidence for the role of nutrient signalling in acne pathogenesis. Acta Derm Venereol. 2012;92:228–31.PubMedCrossRef
28.
go back to reference Melnik BC, John SM, Plewig G. Acne: risk indicator for increased body mass index and insulin resistance. Acta Derm Venereol. 2013;93:644–9.PubMedCrossRef Melnik BC, John SM, Plewig G. Acne: risk indicator for increased body mass index and insulin resistance. Acta Derm Venereol. 2013;93:644–9.PubMedCrossRef
31.
go back to reference Kligman AM. How to use topical tretinoin in treating acne. Cutis. 1995;56:83–4.PubMed Kligman AM. How to use topical tretinoin in treating acne. Cutis. 1995;56:83–4.PubMed
32.
33.
go back to reference Zheng P, Gendimenico GJ, Mezick JA, Kligman AM. Topical all-trans retinoic acid rapidly corrects the follicular abnormalities of the rhino mouse. An ultrastructural study. Acta Derm Venereol. 1993;73:97–101.PubMed Zheng P, Gendimenico GJ, Mezick JA, Kligman AM. Topical all-trans retinoic acid rapidly corrects the follicular abnormalities of the rhino mouse. An ultrastructural study. Acta Derm Venereol. 1993;73:97–101.PubMed
34.
go back to reference Um SJ, Kim EJ, Hwang ES, Kim SJ, Namkoong SE, Park JS. Antiproliferative effects of retinoic acid/interferon in cervical carcinoma cell lines: cooperative growth suppression of IRF-1 and p53. Int J Cancer. 2000;85:416–23.PubMedCrossRef Um SJ, Kim EJ, Hwang ES, Kim SJ, Namkoong SE, Park JS. Antiproliferative effects of retinoic acid/interferon in cervical carcinoma cell lines: cooperative growth suppression of IRF-1 and p53. Int J Cancer. 2000;85:416–23.PubMedCrossRef
35.
go back to reference Zheng A, Mäntymaa P, Säily M, Savolainen E, Vähäkangas K, Koistinen P. p53 pathway in apoptosis induced by all-trans-retinoic acid in acute myeloblastic leukaemia cells. Acta Haematol. 2000;103:135–43.PubMedCrossRef Zheng A, Mäntymaa P, Säily M, Savolainen E, Vähäkangas K, Koistinen P. p53 pathway in apoptosis induced by all-trans-retinoic acid in acute myeloblastic leukaemia cells. Acta Haematol. 2000;103:135–43.PubMedCrossRef
36.
go back to reference Curtin JC, Dragnev KH, Sekula D, Christie AJ, Dmitrovsky E, Spinella MJ. Retinoic acid activates p53 in human embryonal carcinoma through retinoid receptor-dependent stimulation of p53 transactivation function. Oncogene. 2001;20:2559–69.PubMedCrossRef Curtin JC, Dragnev KH, Sekula D, Christie AJ, Dmitrovsky E, Spinella MJ. Retinoic acid activates p53 in human embryonal carcinoma through retinoid receptor-dependent stimulation of p53 transactivation function. Oncogene. 2001;20:2559–69.PubMedCrossRef
37.
go back to reference Lu J, Zhang F, Yuan Y, Ding C, Zhang L, Li Q. All-trans retinoic acid upregulates the expression of p53 via axin and inhibits the proliferation of glioma cells. Oncol Rep. 2013;29:2269–74.PubMedCrossRef Lu J, Zhang F, Yuan Y, Ding C, Zhang L, Li Q. All-trans retinoic acid upregulates the expression of p53 via axin and inhibits the proliferation of glioma cells. Oncol Rep. 2013;29:2269–74.PubMedCrossRef
38.
go back to reference Jain AK, Allton K, Iacovino M, Mahen E, Milczarek RJ, Zwaka TP, et al. p53 regulates cell cycle and microRNAs to promote differentiation of human embryonic stem cells. PLoS Biol. 2012;10:e1001268.PubMedPubMedCentralCrossRef Jain AK, Allton K, Iacovino M, Mahen E, Milczarek RJ, Zwaka TP, et al. p53 regulates cell cycle and microRNAs to promote differentiation of human embryonic stem cells. PLoS Biol. 2012;10:e1001268.PubMedPubMedCentralCrossRef
39.
go back to reference Lee DD, Stojadinovic O, Krzyzanowska A, Vouthounis C, Blumenberg M, Tomic-Canic M. Retinoid-responsive transcriptional changes in epidermal keratinocytes. J Cell Physiol. 2009;220:427–39.PubMedPubMedCentralCrossRef Lee DD, Stojadinovic O, Krzyzanowska A, Vouthounis C, Blumenberg M, Tomic-Canic M. Retinoid-responsive transcriptional changes in epidermal keratinocytes. J Cell Physiol. 2009;220:427–39.PubMedPubMedCentralCrossRef
40.
go back to reference Mrass P, Rendl M, Mildner M, Gruber F, Lengauer B, Ballaun C, et al. Retinoic acid increases the expression of p53 and proapoptotic caspases and sensitizes keratinocytes to apoptosis: a possible explanation for tumor preventive action of retinoids. Cancer Res. 2004;64:6542–8.PubMedCrossRef Mrass P, Rendl M, Mildner M, Gruber F, Lengauer B, Ballaun C, et al. Retinoic acid increases the expression of p53 and proapoptotic caspases and sensitizes keratinocytes to apoptosis: a possible explanation for tumor preventive action of retinoids. Cancer Res. 2004;64:6542–8.PubMedCrossRef
41.
go back to reference Kim J, Nakasaki M, Todorova D, Lake B, Yuan CY, Jamora C, et al. p53 induces skin aging by depleting Blimp1+ sebaceous gland cells. Cell Death Dis. 2014;5:e1141.PubMedPubMedCentralCrossRef Kim J, Nakasaki M, Todorova D, Lake B, Yuan CY, Jamora C, et al. p53 induces skin aging by depleting Blimp1+ sebaceous gland cells. Cell Death Dis. 2014;5:e1141.PubMedPubMedCentralCrossRef
42.
45.
go back to reference Heyne K, Winter C, Gerten F, Schmidt C, Roemer K. A novel mechanism of crosstalk between the p53 and NFκB pathways: MDM2 binds and inhibits p65RelA. Cell Cycle. 2013;12:2479–92.PubMedPubMedCentralCrossRef Heyne K, Winter C, Gerten F, Schmidt C, Roemer K. A novel mechanism of crosstalk between the p53 and NFκB pathways: MDM2 binds and inhibits p65RelA. Cell Cycle. 2013;12:2479–92.PubMedPubMedCentralCrossRef
46.
go back to reference Mehta K. Retinoic acid—a player that rules the game of life and death in neutrophils. Indian J Exp Biol. 2002;40:874–81.PubMed Mehta K. Retinoic acid—a player that rules the game of life and death in neutrophils. Indian J Exp Biol. 2002;40:874–81.PubMed
47.
go back to reference Channabasappa S, Stewart S, Caldwell S, Carr A, Singh B. Retinoic acid induces apoptosis in activated canine neutrophils. Vet Immunol Immunopathol. 2014;157:175–81.PubMedCrossRef Channabasappa S, Stewart S, Caldwell S, Carr A, Singh B. Retinoic acid induces apoptosis in activated canine neutrophils. Vet Immunol Immunopathol. 2014;157:175–81.PubMedCrossRef
48.
go back to reference Duquette SC, Fischer CD, Feener TD, Muench GP, Morck DW, Barreda DR, et al. Anti-inflammatory effects of retinoids and carotenoid derivatives on caspase-3-dependent apoptosis and efferocytosis of bovine neutrophils. Am J Vet Res. 2014;75:1064–75.PubMedCrossRef Duquette SC, Fischer CD, Feener TD, Muench GP, Morck DW, Barreda DR, et al. Anti-inflammatory effects of retinoids and carotenoid derivatives on caspase-3-dependent apoptosis and efferocytosis of bovine neutrophils. Am J Vet Res. 2014;75:1064–75.PubMedCrossRef
49.
go back to reference Nawata H, Maeda Y, Sumimoto Y, Miyatake J, Kanamaru A. A mechanism of apoptosis induced by all-trans retinoic acid on adult T-cell leukemia cells: a possible involvement of the Tax/NF-kappaB signaling pathway. Leuk Res. 2001;25:323–31.PubMedCrossRef Nawata H, Maeda Y, Sumimoto Y, Miyatake J, Kanamaru A. A mechanism of apoptosis induced by all-trans retinoic acid on adult T-cell leukemia cells: a possible involvement of the Tax/NF-kappaB signaling pathway. Leuk Res. 2001;25:323–31.PubMedCrossRef
50.
go back to reference Fulton JE Jr, Farzad-Bakshandeh A, Bradley S. Studies on the mechanism of action to topical benzoyl peroxide and vitamin A acid in acne vulgaris. J Cutan Pathol. 1974;1:191–200.PubMedCrossRef Fulton JE Jr, Farzad-Bakshandeh A, Bradley S. Studies on the mechanism of action to topical benzoyl peroxide and vitamin A acid in acne vulgaris. J Cutan Pathol. 1974;1:191–200.PubMedCrossRef
51.
go back to reference Oh CW, Myung KB. An ultrastructural study of the retention hyperkeratosis of experimentally induced comedones in rabbits: the effects of three comedolytics. J Dermatol. 1996;23:169–80.PubMedCrossRef Oh CW, Myung KB. An ultrastructural study of the retention hyperkeratosis of experimentally induced comedones in rabbits: the effects of three comedolytics. J Dermatol. 1996;23:169–80.PubMedCrossRef
52.
go back to reference Waller JM, Dreher F, Behnam S, Ford C, Lee C, Tiet T, et al. ‘Keratolytic’ properties of benzoyl peroxide and retinoic acid resemble salicylic acid in man. Skin Pharmacol Physiol. 2006;19:283–9.PubMedCrossRef Waller JM, Dreher F, Behnam S, Ford C, Lee C, Tiet T, et al. ‘Keratolytic’ properties of benzoyl peroxide and retinoic acid resemble salicylic acid in man. Skin Pharmacol Physiol. 2006;19:283–9.PubMedCrossRef
53.
go back to reference Gloor M, Klump H, Wirth H. Cytokinetic studies on the sebo-suppressive effect of drugs using the example of benzoyl peroxide. Arch Dermatol Res. 1980;267:97–9.PubMedCrossRef Gloor M, Klump H, Wirth H. Cytokinetic studies on the sebo-suppressive effect of drugs using the example of benzoyl peroxide. Arch Dermatol Res. 1980;267:97–9.PubMedCrossRef
54.
go back to reference Fanta D. Klinische und experimentelle Untersuchungen über die Wirkung von Benzoylperoxid in der Behandlung der Akne. Hautarzt. 1978;29:481–6.PubMed Fanta D. Klinische und experimentelle Untersuchungen über die Wirkung von Benzoylperoxid in der Behandlung der Akne. Hautarzt. 1978;29:481–6.PubMed
55.
go back to reference Wirth H, Spürgel D, Gloor M. Untersuchungen zur Wirkung von Benzoylperoxid auf die Talgdrüsensekretion. Dermatol Monatsschr. 1983;169:289–93.PubMed Wirth H, Spürgel D, Gloor M. Untersuchungen zur Wirkung von Benzoylperoxid auf die Talgdrüsensekretion. Dermatol Monatsschr. 1983;169:289–93.PubMed
56.
go back to reference Puschmann M. Klinisch-experimentelle Untersuchungen zum Wirkungsmechanismus von Benzoylperoxid. Hautarzt. 1982;33:257–65.PubMed Puschmann M. Klinisch-experimentelle Untersuchungen zum Wirkungsmechanismus von Benzoylperoxid. Hautarzt. 1982;33:257–65.PubMed
57.
go back to reference Mezick JA, Thorne EG, Bhatia MC, Shea LM, Capetola JR. The rabbit ear microcomedo prevention assay. A new model to evaluate antiacne agents. In: Maibach HI, Lowe NJ, editors. Models in Dermatology, vol 3. Karger: Basel, München, Paris, London, New York, New Delhi, Singapore, Tokyo, Sydney; 1987. p. 68–73. Mezick JA, Thorne EG, Bhatia MC, Shea LM, Capetola JR. The rabbit ear microcomedo prevention assay. A new model to evaluate antiacne agents. In: Maibach HI, Lowe NJ, editors. Models in Dermatology, vol 3. Karger: Basel, München, Paris, London, New York, New Delhi, Singapore, Tokyo, Sydney; 1987. p. 68–73.
58.
go back to reference Valacchi G, Rimbach G, Saliou C, Weber SU, Packer L. Effect of benzoyl peroxide on antioxidant status, NF-kappaB activity and interleukin-1alpha gene expression in human keratinocytes. Toxicology. 2001;165:225–34.PubMedCrossRef Valacchi G, Rimbach G, Saliou C, Weber SU, Packer L. Effect of benzoyl peroxide on antioxidant status, NF-kappaB activity and interleukin-1alpha gene expression in human keratinocytes. Toxicology. 2001;165:225–34.PubMedCrossRef
59.
go back to reference Kennedy CH, Winston GW, Church DF, Pryor WA. Benzoyl peroxide interaction with mitochondria: inhibition of respiration and induction of rapid, large-amplitude swelling. Arch Biochem Biophys. 1989;271:456–70.PubMedCrossRef Kennedy CH, Winston GW, Church DF, Pryor WA. Benzoyl peroxide interaction with mitochondria: inhibition of respiration and induction of rapid, large-amplitude swelling. Arch Biochem Biophys. 1989;271:456–70.PubMedCrossRef
60.
go back to reference Milani M, Bigardi A, Zavattarelli M. Efficacy and safety of stabilized hydrogen peroxide cream (Crystacide®) in mild-to-moderate acne vulgaris: a randomized, controlled trial versus benzoyl peroxide gel. Curr Med Res Opin. 2003;19:135–8.PubMedCrossRef Milani M, Bigardi A, Zavattarelli M. Efficacy and safety of stabilized hydrogen peroxide cream (Crystacide®) in mild-to-moderate acne vulgaris: a randomized, controlled trial versus benzoyl peroxide gel. Curr Med Res Opin. 2003;19:135–8.PubMedCrossRef
61.
go back to reference Muizzuddin N, Schnittger S, Maher W, Maes DH, Mammone T. Enzymatically generated hydrogen peroxide reduces the number of acne lesions in acne vulgaris. J Cosmet Sci. 2013;64:1–8.PubMed Muizzuddin N, Schnittger S, Maher W, Maes DH, Mammone T. Enzymatically generated hydrogen peroxide reduces the number of acne lesions in acne vulgaris. J Cosmet Sci. 2013;64:1–8.PubMed
62.
go back to reference Veraldi S, Micali G, Berardesca E, Dall’Oglio F, Sinagra JL, Guanziroli E. Results of a multicenter, randomized, controlled trial of a hydrogen peroxide-based kit versus a benzoyl peroxide-based kit in mild-to-moderate acne. J Clin Aesthet Dermatol. 2016;9:50–4.PubMedPubMedCentral Veraldi S, Micali G, Berardesca E, Dall’Oglio F, Sinagra JL, Guanziroli E. Results of a multicenter, randomized, controlled trial of a hydrogen peroxide-based kit versus a benzoyl peroxide-based kit in mild-to-moderate acne. J Clin Aesthet Dermatol. 2016;9:50–4.PubMedPubMedCentral
63.
go back to reference Pronsato L, Milanesi L. Effect of testosterone on the regulation of p53 and p66Shc during oxidative stress damage in C2C12 cells. Steroids. 2016;106:41–54.PubMedCrossRef Pronsato L, Milanesi L. Effect of testosterone on the regulation of p53 and p66Shc during oxidative stress damage in C2C12 cells. Steroids. 2016;106:41–54.PubMedCrossRef
65.
go back to reference Budanov AV, Sablina AA, Feinstein E, Koonin EV, Chumakov PM. Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD. Science. 2004;304:596–600.PubMedCrossRef Budanov AV, Sablina AA, Feinstein E, Koonin EV, Chumakov PM. Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD. Science. 2004;304:596–600.PubMedCrossRef
66.
go back to reference Lee JH, Budanov AV, Park EJ, Birse R, Kim TE, Perkins GA, et al. Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science. 2010;327:1223–8.PubMedPubMedCentralCrossRef Lee JH, Budanov AV, Park EJ, Birse R, Kim TE, Perkins GA, et al. Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science. 2010;327:1223–8.PubMedPubMedCentralCrossRef
67.
go back to reference Budanov AV. Stress-responsive sestrins link p53 with redox regulation and mammalian target of rapamycin signaling. Antioxid Redox Signal. 2011;15:1679–90.PubMedPubMedCentralCrossRef Budanov AV. Stress-responsive sestrins link p53 with redox regulation and mammalian target of rapamycin signaling. Antioxid Redox Signal. 2011;15:1679–90.PubMedPubMedCentralCrossRef
68.
go back to reference Fabbrocini G, Izzo R, Faggiano A, Del Prete M, Donnarumma M, Marasca C, et al. Low glycaemic diet and metformin therapy: a new approach in male subjects with acne resistant to common treatments. Clin Exp Dermatol. 2016;41:38–42.PubMedCrossRef Fabbrocini G, Izzo R, Faggiano A, Del Prete M, Donnarumma M, Marasca C, et al. Low glycaemic diet and metformin therapy: a new approach in male subjects with acne resistant to common treatments. Clin Exp Dermatol. 2016;41:38–42.PubMedCrossRef
69.
go back to reference Melnik BC, Schmitz G. Metformin: an inhibitor of mTORC1 signaling. J Endocrinol Diabetes Obes. 2014;2:1029. Melnik BC, Schmitz G. Metformin: an inhibitor of mTORC1 signaling. J Endocrinol Diabetes Obes. 2014;2:1029.
70.
go back to reference Shafiee MN, Malik DA, Yunos RI, Atiomo W, Omar MH, Ghani NA, et al. The effect of metformin on endometrial tumor-regulatory genes and systemic metabolic parameters in polycystic ovarian syndrome—a proof-of-concept study. Gynecol Endocrinol. 2015;31:286–90.PubMedCrossRef Shafiee MN, Malik DA, Yunos RI, Atiomo W, Omar MH, Ghani NA, et al. The effect of metformin on endometrial tumor-regulatory genes and systemic metabolic parameters in polycystic ovarian syndrome—a proof-of-concept study. Gynecol Endocrinol. 2015;31:286–90.PubMedCrossRef
71.
go back to reference Boen M, Brownell J, Patel P, Tsoukas MM. The role of photodynamic therapy in acne: an evidence-based review. Am J Clin Dermatol. 2017;18:311–21.PubMedCrossRef Boen M, Brownell J, Patel P, Tsoukas MM. The role of photodynamic therapy in acne: an evidence-based review. Am J Clin Dermatol. 2017;18:311–21.PubMedCrossRef
72.
go back to reference Fonda-Pascual P, Moreno-Arrones OM, Alegre-Sanchez A, Saceda-Corralo D, Buendia-Castaño D, Pindado-Ortega C, et al. In situ production of ROS in the skin by photodynamic therapy as a powerful tool in clinical dermatology. Methods. 2016;109:190–202.PubMedCrossRef Fonda-Pascual P, Moreno-Arrones OM, Alegre-Sanchez A, Saceda-Corralo D, Buendia-Castaño D, Pindado-Ortega C, et al. In situ production of ROS in the skin by photodynamic therapy as a powerful tool in clinical dermatology. Methods. 2016;109:190–202.PubMedCrossRef
73.
go back to reference Zuliani T, Khammari A, Chaussy H, Knol AC, Dréno B. Ex vivo demonstration of a synergistic effect of Adapalene and benzoyl peroxide on inflammatory acne lesions. Exp Dermatol. 2011;20:850–3.PubMedCrossRef Zuliani T, Khammari A, Chaussy H, Knol AC, Dréno B. Ex vivo demonstration of a synergistic effect of Adapalene and benzoyl peroxide on inflammatory acne lesions. Exp Dermatol. 2011;20:850–3.PubMedCrossRef
74.
go back to reference Shemer A, Weiss G, Amichai B, Kaplan B, Trau H. Azelaic acid (20%) cream in the treatment of acne vulgaris. J Eur Acad Dermatol Venereol. 2002;16:178–9.PubMedCrossRef Shemer A, Weiss G, Amichai B, Kaplan B, Trau H. Azelaic acid (20%) cream in the treatment of acne vulgaris. J Eur Acad Dermatol Venereol. 2002;16:178–9.PubMedCrossRef
75.
go back to reference Schulte BC, Wu W, Rosen T. Azelaic acid: evidence-based update on mechanism of action and clinical application. J Drugs Dermatol. 2015;14:964–8.PubMed Schulte BC, Wu W, Rosen T. Azelaic acid: evidence-based update on mechanism of action and clinical application. J Drugs Dermatol. 2015;14:964–8.PubMed
76.
go back to reference Mayer-da Silva A, Gollnick H, Imcke E, Orfanos CE. Azelaic acid vs. placebo: effects on normal human keratinocytes and melanocytes. Electron microscopic evaluation after long-term application in vivo. Acta Derm Venereol. 1987;67:116–22.PubMed Mayer-da Silva A, Gollnick H, Imcke E, Orfanos CE. Azelaic acid vs. placebo: effects on normal human keratinocytes and melanocytes. Electron microscopic evaluation after long-term application in vivo. Acta Derm Venereol. 1987;67:116–22.PubMed
77.
go back to reference Detmar M, Mayer-da-Silva A, Stadler R, Orfanos CE. Effects of azelaic acid on proliferation and ultrastructure of mouse keratinocytes in vitro. J Invest Dermatol. 1989;93:70–4.PubMedCrossRef Detmar M, Mayer-da-Silva A, Stadler R, Orfanos CE. Effects of azelaic acid on proliferation and ultrastructure of mouse keratinocytes in vitro. J Invest Dermatol. 1989;93:70–4.PubMedCrossRef
78.
go back to reference Mayer-da-Silva A, Gollnick H, Detmar M, Gassmüller J, Parry A, Müller R, et al. Effects of azelaic acid on sebaceous gland, sebum excretion rate and keratinization pattern in human skin. An in vivo and in vitro study. Acta Derm Venereol Suppl (Stockh). 1989;143:20–30. Mayer-da-Silva A, Gollnick H, Detmar M, Gassmüller J, Parry A, Müller R, et al. Effects of azelaic acid on sebaceous gland, sebum excretion rate and keratinization pattern in human skin. An in vivo and in vitro study. Acta Derm Venereol Suppl (Stockh). 1989;143:20–30.
79.
go back to reference Passi S, Picardo M, Nazzaro-Porro M, Breathnach A, Confaloni AM, Serlupi- Crescenzi G. Antimitochondrial effect of saturated medium chain length (C8–C13) dicarboxylic acids. Biochem Pharmacol. 1984;33:103–8.PubMedCrossRef Passi S, Picardo M, Nazzaro-Porro M, Breathnach A, Confaloni AM, Serlupi- Crescenzi G. Antimitochondrial effect of saturated medium chain length (C8–C13) dicarboxylic acids. Biochem Pharmacol. 1984;33:103–8.PubMedCrossRef
80.
go back to reference Chen R, Yang L, McIntyre TM. Cytotoxic phospholipid oxidation products. Cell death from mitochondrial damage and the intrinsic caspase cascade. J Biol Chem. 2007;282:24842–50.PubMedPubMedCentralCrossRef Chen R, Yang L, McIntyre TM. Cytotoxic phospholipid oxidation products. Cell death from mitochondrial damage and the intrinsic caspase cascade. J Biol Chem. 2007;282:24842–50.PubMedPubMedCentralCrossRef
82.
83.
go back to reference Del Rosso JQ. Topical and oral antibiotics for acne vulgaris. Semin Cutan Med Surg. 2016;35:57–61.PubMedCrossRef Del Rosso JQ. Topical and oral antibiotics for acne vulgaris. Semin Cutan Med Surg. 2016;35:57–61.PubMedCrossRef
84.
go back to reference Perret LJ, Tait CP. Non-antibiotic properties of tetracyclines and their clinical application in dermatology. Australas J Dermatol. 2014;55:111–8.PubMedCrossRef Perret LJ, Tait CP. Non-antibiotic properties of tetracyclines and their clinical application in dermatology. Australas J Dermatol. 2014;55:111–8.PubMedCrossRef
85.
go back to reference Moore A, Ling M, Bucko A, Manna V, Rueda MJ. Efficacy and safety of subantimicrobial dose, modified-release doxycycline 40 mg versus doxycycline 100 mg versus placebo for the treatment of inflammatory lesions in moderate and severe acne: a randomized, double-blinded, controlled study. J Drugs Dermatol. 2015;14:581–6.PubMed Moore A, Ling M, Bucko A, Manna V, Rueda MJ. Efficacy and safety of subantimicrobial dose, modified-release doxycycline 40 mg versus doxycycline 100 mg versus placebo for the treatment of inflammatory lesions in moderate and severe acne: a randomized, double-blinded, controlled study. J Drugs Dermatol. 2015;14:581–6.PubMed
86.
go back to reference Mollan SP, Ali F, Hassan-Smith G, Botfield H, Friedman DI, Alexandra J, et al. Evolving evidence in adult idiopathic intracranial hypertension: pathophysiology and management. J Neurol Neurosurg Psychiatry. 2016;87:982–92.PubMedPubMedCentralCrossRef Mollan SP, Ali F, Hassan-Smith G, Botfield H, Friedman DI, Alexandra J, et al. Evolving evidence in adult idiopathic intracranial hypertension: pathophysiology and management. J Neurol Neurosurg Psychiatry. 2016;87:982–92.PubMedPubMedCentralCrossRef
87.
go back to reference Regen F, Le Bret N, Hildebrand M, Herzog I, Heuser I, Hellmann-Regen J. Inhibition of brain retinoic acid catabolism: a mechanism for minocycline’s pleiotropic actions? World J Biol Psychiatry. 2016;17:634–40.PubMed Regen F, Le Bret N, Hildebrand M, Herzog I, Heuser I, Hellmann-Regen J. Inhibition of brain retinoic acid catabolism: a mechanism for minocycline’s pleiotropic actions? World J Biol Psychiatry. 2016;17:634–40.PubMed
88.
go back to reference Hellmann-Regen J, Herzog I, Fischer N, Heuser I, Regen F. Do tetracyclines and erythromycin exert anti-acne effects by inhibition of P450-mediated degradation of retinoic acid? Exp Dermatol. 2014;23:290–3.PubMedCrossRef Hellmann-Regen J, Herzog I, Fischer N, Heuser I, Regen F. Do tetracyclines and erythromycin exert anti-acne effects by inhibition of P450-mediated degradation of retinoic acid? Exp Dermatol. 2014;23:290–3.PubMedCrossRef
89.
go back to reference Regen F, Hildebrand M, Le Bret N, Herzog I, Heuser I, Hellmann-Regen J. Inhibition of retinoic acid catabolism by minocycline: evidence for a novel mode of action? Exp Dermatol. 2015;24:473–6.PubMedCrossRef Regen F, Hildebrand M, Le Bret N, Herzog I, Heuser I, Hellmann-Regen J. Inhibition of retinoic acid catabolism by minocycline: evidence for a novel mode of action? Exp Dermatol. 2015;24:473–6.PubMedCrossRef
90.
go back to reference Zhu Z, Hotchkiss SA, Boobis AR, Edwards RJ. Expression of P450 enzymes in rat whole skin and cultured epidermal keratinocytes. Biochem Biophys Res Commun. 2002;297:65–70.PubMedCrossRef Zhu Z, Hotchkiss SA, Boobis AR, Edwards RJ. Expression of P450 enzymes in rat whole skin and cultured epidermal keratinocytes. Biochem Biophys Res Commun. 2002;297:65–70.PubMedCrossRef
91.
go back to reference Burt HJ, Galetin A, Houston JB. IC50-based approaches as an alternative method for assessment of time-dependent inhibition of CYP3A4. Xenobiotica. 2010;40:331–43.PubMedCrossRef Burt HJ, Galetin A, Houston JB. IC50-based approaches as an alternative method for assessment of time-dependent inhibition of CYP3A4. Xenobiotica. 2010;40:331–43.PubMedCrossRef
93.
94.
go back to reference Ataie-Kachoie P, Pourgholami MH, Bahrami-B F, Badar S, Morris DL. Minocycline attenuates hypoxia-inducible factor-1α expression correlated with modulation of p53 and AKT/mTOR/p70S6K/4E-BP1 pathway in ovarian cancer: in vitro and in vivo studies. Am J Cancer Res. 2015;5:575–88.PubMedPubMedCentral Ataie-Kachoie P, Pourgholami MH, Bahrami-B F, Badar S, Morris DL. Minocycline attenuates hypoxia-inducible factor-1α expression correlated with modulation of p53 and AKT/mTOR/p70S6K/4E-BP1 pathway in ovarian cancer: in vitro and in vivo studies. Am J Cancer Res. 2015;5:575–88.PubMedPubMedCentral
95.
go back to reference Lee MD, Ayanoglu E, Gong L. Drug-induced changes in P450 enzyme expression at the gene expression level: a new dimension to the analysis of drug-drug interactions. Xenobiotica. 2006;36:1013–80.PubMedCrossRef Lee MD, Ayanoglu E, Gong L. Drug-induced changes in P450 enzyme expression at the gene expression level: a new dimension to the analysis of drug-drug interactions. Xenobiotica. 2006;36:1013–80.PubMedCrossRef
96.
go back to reference Lynch T, Price A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Phys. 2007;76:391–6. Lynch T, Price A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Phys. 2007;76:391–6.
97.
go back to reference Matoulková P, Pávek P, Malý J, Vlček J. Cytochrome P450 enzyme regulation by glucocorticoids and consequences in terms of drug interaction. Expert Opin Drug Metab Toxicol. 2014;10:425–35.PubMedCrossRef Matoulková P, Pávek P, Malý J, Vlček J. Cytochrome P450 enzyme regulation by glucocorticoids and consequences in terms of drug interaction. Expert Opin Drug Metab Toxicol. 2014;10:425–35.PubMedCrossRef
98.
go back to reference Momin SB, Peterson A, Del Rosso JQ. A status report on drug-associated acne and acneiform eruptions. J Drugs Dermatol. 2010;9:627–36.PubMed Momin SB, Peterson A, Del Rosso JQ. A status report on drug-associated acne and acneiform eruptions. J Drugs Dermatol. 2010;9:627–36.PubMed
99.
go back to reference Du-Thanh A, Kluger N, Bensalleh H, Guillot B. Drug-induced acneiform eruption. Am J Clin Dermatol. 2011;12:233–45.PubMedCrossRef Du-Thanh A, Kluger N, Bensalleh H, Guillot B. Drug-induced acneiform eruption. Am J Clin Dermatol. 2011;12:233–45.PubMedCrossRef
101.
go back to reference Peck GL, Olsen TG, Yoder FW, Strauss JS, Downing DT, Pandya M, et al. Prolonged remissions of cystic and conglobate acne with 13-cis-retinoic acid. N Engl J Med. 1979;300:329–33.PubMedCrossRef Peck GL, Olsen TG, Yoder FW, Strauss JS, Downing DT, Pandya M, et al. Prolonged remissions of cystic and conglobate acne with 13-cis-retinoic acid. N Engl J Med. 1979;300:329–33.PubMedCrossRef
102.
go back to reference Strauss JS, Stranieri AM. Changes in long-term sebum production from isotretinoin therapy. J Am Acad Dermatol. 1982;6(4 Pt 2 Suppl):751–6.PubMedCrossRef Strauss JS, Stranieri AM. Changes in long-term sebum production from isotretinoin therapy. J Am Acad Dermatol. 1982;6(4 Pt 2 Suppl):751–6.PubMedCrossRef
103.
go back to reference Melnik B, Kinner T, Plewig G. Influence of oral isotretinoin treatment on the composition of comedonal lipids. Implications for comedogenesis in acne vulgaris. Arch Dermatol Res. 1988;280:97–102.PubMedCrossRef Melnik B, Kinner T, Plewig G. Influence of oral isotretinoin treatment on the composition of comedonal lipids. Implications for comedogenesis in acne vulgaris. Arch Dermatol Res. 1988;280:97–102.PubMedCrossRef
104.
go back to reference Plewig G, Wagner A. Anti-inflammatory effects of 13-cis-retinoic acid. An in vivo study. Arch Dermatol Res. 1981;270:89–94.PubMedCrossRef Plewig G, Wagner A. Anti-inflammatory effects of 13-cis-retinoic acid. An in vivo study. Arch Dermatol Res. 1981;270:89–94.PubMedCrossRef
105.
go back to reference Strauss JS, Stewart ME, Downing DT. The effect of 13-cis-retinoic acid on sebaceous glands. Arch Dermatol. 1987;123:1538a–41a.PubMedCrossRef Strauss JS, Stewart ME, Downing DT. The effect of 13-cis-retinoic acid on sebaceous glands. Arch Dermatol. 1987;123:1538a–41a.PubMedCrossRef
106.
go back to reference Kelhälä HL, Fyhrquist N, Palatsi R, Lehtimäki S, Väyrynen JP, Kubin ME, et al. Isotretinoin treatment reduces acne lesions but not directly lesional acne inflammation. Exp Dermatol. 2016;25:477–8.PubMedCrossRef Kelhälä HL, Fyhrquist N, Palatsi R, Lehtimäki S, Väyrynen JP, Kubin ME, et al. Isotretinoin treatment reduces acne lesions but not directly lesional acne inflammation. Exp Dermatol. 2016;25:477–8.PubMedCrossRef
107.
go back to reference Landthaler M, Kummermehr J, Wagner A, Plewig G. Inhibitory effects of 13-cis-retinoic acid on human sebaceous glands. Arch Dermatol Res. 1980;269:297–309.PubMedCrossRef Landthaler M, Kummermehr J, Wagner A, Plewig G. Inhibitory effects of 13-cis-retinoic acid on human sebaceous glands. Arch Dermatol Res. 1980;269:297–309.PubMedCrossRef
108.
go back to reference Nelson AM, Zhao W, Gilliland KL, Zaenglein AL, Liu W, Thiboutot DM. Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinology. 2009;1:177–87.CrossRef Nelson AM, Zhao W, Gilliland KL, Zaenglein AL, Liu W, Thiboutot DM. Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinology. 2009;1:177–87.CrossRef
109.
go back to reference Tsukada M, Schröder M, Roos TC, Chandraratna RA, Reichert U, Merk HF, et al. 13-cis retinoic acid exerts its specific activity on human sebocytes through selective intracellular isomerization to all-trans retinoic acid and binding to retinoid acid receptors. J Invest Dermatol. 2000;115:321–7.PubMedCrossRef Tsukada M, Schröder M, Roos TC, Chandraratna RA, Reichert U, Merk HF, et al. 13-cis retinoic acid exerts its specific activity on human sebocytes through selective intracellular isomerization to all-trans retinoic acid and binding to retinoid acid receptors. J Invest Dermatol. 2000;115:321–7.PubMedCrossRef
110.
go back to reference Kuribayashi K, Krigsfeld G, Wang W, Xu J, Mayes PA, Dicker DT, et al. TNFSF10 (TRAIL), a p53 target gene that mediates p53-dependent cell death. Cancer Biol Ther. 2008;7:2034–8.PubMedCrossRef Kuribayashi K, Krigsfeld G, Wang W, Xu J, Mayes PA, Dicker DT, et al. TNFSF10 (TRAIL), a p53 target gene that mediates p53-dependent cell death. Cancer Biol Ther. 2008;7:2034–8.PubMedCrossRef
111.
go back to reference Dhandapani L, Yue P, Ramalingam SS, Khuri FR, Sun SY. Retinoic acid enhances TRAIL-induced apoptosis in cancer cells by upregulating TRAIL receptor 1 expression. Cancer Res. 2011;71:5245–54.PubMedPubMedCentralCrossRef Dhandapani L, Yue P, Ramalingam SS, Khuri FR, Sun SY. Retinoic acid enhances TRAIL-induced apoptosis in cancer cells by upregulating TRAIL receptor 1 expression. Cancer Res. 2011;71:5245–54.PubMedPubMedCentralCrossRef
112.
go back to reference Kim MJ, Ahn K, Park SH, Kang HJ, Jang BG, Oh SJ, et al. SIRT1 regulates tyrosine hydroxylase expression and differentiation of neuroblastoma cells via FOXO3a. FEBS Lett. 2009;583:1183–8.PubMedCrossRef Kim MJ, Ahn K, Park SH, Kang HJ, Jang BG, Oh SJ, et al. SIRT1 regulates tyrosine hydroxylase expression and differentiation of neuroblastoma cells via FOXO3a. FEBS Lett. 2009;583:1183–8.PubMedCrossRef
113.
go back to reference Sakoe Y, Sakoe K, Kirito K, Ozawa K, Komatsu N. FOXO3A as a key molecule for all-trans retinoic acid-induced granulocytic differentiation and apoptosis in acute promyelocytic leukemia. Blood. 2010;115:3787–95.PubMedCrossRef Sakoe Y, Sakoe K, Kirito K, Ozawa K, Komatsu N. FOXO3A as a key molecule for all-trans retinoic acid-induced granulocytic differentiation and apoptosis in acute promyelocytic leukemia. Blood. 2010;115:3787–95.PubMedCrossRef
114.
go back to reference Kurinna S, Stratton SA, Tsai WW, Akdemir KC, Gu W, Singh P, et al. Direct activation of forkhead box O3 by tumor suppressors p53 and p73 is disrupted during liver regeneration in mice. Hepatology. 2010;52:1023–32.PubMedPubMedCentralCrossRef Kurinna S, Stratton SA, Tsai WW, Akdemir KC, Gu W, Singh P, et al. Direct activation of forkhead box O3 by tumor suppressors p53 and p73 is disrupted during liver regeneration in mice. Hepatology. 2010;52:1023–32.PubMedPubMedCentralCrossRef
115.
go back to reference Renault VM, Thekkat PU, Hoang KL, White JL, Brady CA, Kenzelmann Broz D, et al. The pro-longevity gene FoxO3 is a direct target of the p53 tumor suppressor. Oncogene. 2011;30:3207–21.PubMedPubMedCentralCrossRef Renault VM, Thekkat PU, Hoang KL, White JL, Brady CA, Kenzelmann Broz D, et al. The pro-longevity gene FoxO3 is a direct target of the p53 tumor suppressor. Oncogene. 2011;30:3207–21.PubMedPubMedCentralCrossRef
116.
go back to reference Nayak G, Cooper GM. p53 is a major component of the transcriptional and apoptotic program regulated by PI 3-kinase/Akt/GSK3 signaling. Cell Death Dis. 2012;3:e400.PubMedPubMedCentralCrossRef Nayak G, Cooper GM. p53 is a major component of the transcriptional and apoptotic program regulated by PI 3-kinase/Akt/GSK3 signaling. Cell Death Dis. 2012;3:e400.PubMedPubMedCentralCrossRef
118.
go back to reference Zhang X, Tang N, Hadden TJ, Rishi AK. Akt, FoxO and regulation of apoptosis. Biochim Biophys Acta. 2011;1813:1978–86.PubMedCrossRef Zhang X, Tang N, Hadden TJ, Rishi AK. Akt, FoxO and regulation of apoptosis. Biochim Biophys Acta. 2011;1813:1978–86.PubMedCrossRef
119.
go back to reference Nelson AM, Zhao W, Gilliland KL, Zaenglein AL, Liu W, Thiboutot DM. Neutrophil gelatinase-associated lipocalin mediates 13-cis retinoic acid- induced apoptosis of human sebaceous gland cells. J Clin Invest. 2008;118:1468–78.PubMedPubMedCentralCrossRef Nelson AM, Zhao W, Gilliland KL, Zaenglein AL, Liu W, Thiboutot DM. Neutrophil gelatinase-associated lipocalin mediates 13-cis retinoic acid- induced apoptosis of human sebaceous gland cells. J Clin Invest. 2008;118:1468–78.PubMedPubMedCentralCrossRef
120.
go back to reference Nelson AM, Cong Z, Gilliland KL, Thiboutot DM. TRAIL contributes to the apoptotic effect of 13-cis retinoic acid in human sebaceous gland cells. Br J Dermatol. 2011;165:526–33.PubMedPubMedCentralCrossRef Nelson AM, Cong Z, Gilliland KL, Thiboutot DM. TRAIL contributes to the apoptotic effect of 13-cis retinoic acid in human sebaceous gland cells. Br J Dermatol. 2011;165:526–33.PubMedPubMedCentralCrossRef
121.
go back to reference Wu NL, Lee TA, Tsai TL, Lin WW. TRAIL-induced keratinocyte differentiation requires caspase activation and p63 expression. J Invest Dermatol. 2011;131:874–83.PubMedCrossRef Wu NL, Lee TA, Tsai TL, Lin WW. TRAIL-induced keratinocyte differentiation requires caspase activation and p63 expression. J Invest Dermatol. 2011;131:874–83.PubMedCrossRef
122.
go back to reference Tsujita-Kyutoku M, Kiuchi K, Danbara N, Yuri T, Senzaki H, Tsubura A. p63 expression in normal human epidermis and epidermal appendages and their tumors. J Cutan Pathol. 2003;30:11–7.PubMedCrossRef Tsujita-Kyutoku M, Kiuchi K, Danbara N, Yuri T, Senzaki H, Tsubura A. p63 expression in normal human epidermis and epidermal appendages and their tumors. J Cutan Pathol. 2003;30:11–7.PubMedCrossRef
123.
go back to reference Rudman SM, Philpott MP, Thomas GA, Kealey T. The role of IGF-I in human skin and its appendages: morphogen as well as mitogen? J Invest Dermatol. 1997;109:770–7.PubMedCrossRef Rudman SM, Philpott MP, Thomas GA, Kealey T. The role of IGF-I in human skin and its appendages: morphogen as well as mitogen? J Invest Dermatol. 1997;109:770–7.PubMedCrossRef
124.
go back to reference Ben-Amitai D, Laron Z. Effect of insulin-like growth factor-1 deficiency or administration on the occurrence of acne. J Eur Acad Dermatol Venereol. 2011;25:950–4.PubMedCrossRef Ben-Amitai D, Laron Z. Effect of insulin-like growth factor-1 deficiency or administration on the occurrence of acne. J Eur Acad Dermatol Venereol. 2011;25:950–4.PubMedCrossRef
125.
go back to reference Melnik BC, John SM, Schmitz G. Over-stimulation of insulin/IGF-1 signaling by western diet may promote diseases of civilization: lessons learnt from Laron syndrome. Nutr Metab (Lond). 2011;8:41.CrossRef Melnik BC, John SM, Schmitz G. Over-stimulation of insulin/IGF-1 signaling by western diet may promote diseases of civilization: lessons learnt from Laron syndrome. Nutr Metab (Lond). 2011;8:41.CrossRef
126.
127.
go back to reference Plewig G, Fulton JE, Kligman AM. Cellular dynamics of comedo formation in acne vulgaris. Arch Dermatol Forsch. 1971;242:12–29.PubMedCrossRef Plewig G, Fulton JE, Kligman AM. Cellular dynamics of comedo formation in acne vulgaris. Arch Dermatol Forsch. 1971;242:12–29.PubMedCrossRef
128.
go back to reference Werner H, Karnieli E, Rauscher FJ, LeRoith D. Wild-type and mutant p53 differentially regulate transcription of the insulin-like growth factor I receptor gene. Proc Natl Acad Sci USA. 1996;93:8318–23.PubMedPubMedCentralCrossRef Werner H, Karnieli E, Rauscher FJ, LeRoith D. Wild-type and mutant p53 differentially regulate transcription of the insulin-like growth factor I receptor gene. Proc Natl Acad Sci USA. 1996;93:8318–23.PubMedPubMedCentralCrossRef
130.
go back to reference Werner H, Sarfstein R, LeRoith D, Bruchim I. Insulin-like growth factor 1 signaling axis meets p53 genome protection pathways. Front Oncol. 2016;6:159.PubMedPubMedCentralCrossRef Werner H, Sarfstein R, LeRoith D, Bruchim I. Insulin-like growth factor 1 signaling axis meets p53 genome protection pathways. Front Oncol. 2016;6:159.PubMedPubMedCentralCrossRef
131.
go back to reference Hilmi C, Larribere L, Deckert M, Rocchi S, Giuliano S, Bille K, et al. Involvement of FKHRL1 in melanoma cell survival and death. Pigment Cell Melanoma Res. 2008;21:139–46.PubMedCrossRef Hilmi C, Larribere L, Deckert M, Rocchi S, Giuliano S, Bille K, et al. Involvement of FKHRL1 in melanoma cell survival and death. Pigment Cell Melanoma Res. 2008;21:139–46.PubMedCrossRef
132.
go back to reference Kiraz Y, Adan A, Kartal Yandim M, Baran Y. Major apoptotic mechanisms and genes involved in apoptosis. Tumour Biol. 2016;37:8471–86.PubMedCrossRef Kiraz Y, Adan A, Kartal Yandim M, Baran Y. Major apoptotic mechanisms and genes involved in apoptosis. Tumour Biol. 2016;37:8471–86.PubMedCrossRef
134.
go back to reference Nelson AM, Gilliland KL, Cong Z, Thiboutot DM. 13-cis Retinoic acid induces apoptosis and cell cycle arrest in human SEB-1 sebocytes. J Invest Dermatol. 2006;126:2178–89.PubMedCrossRef Nelson AM, Gilliland KL, Cong Z, Thiboutot DM. 13-cis Retinoic acid induces apoptosis and cell cycle arrest in human SEB-1 sebocytes. J Invest Dermatol. 2006;126:2178–89.PubMedCrossRef
135.
go back to reference Boulaire J, Fotedar A, Fotedar R. The functions of the cdk-cyclin kinase inhibitor p21WAF1. Pathol Biol (Paris). 2000;48:190–202. Boulaire J, Fotedar A, Fotedar R. The functions of the cdk-cyclin kinase inhibitor p21WAF1. Pathol Biol (Paris). 2000;48:190–202.
137.
go back to reference el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, et al. WAF1, a potential mediator of p53 tumor suppression. Cell. 1993;75:817–25.PubMedCrossRef el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, et al. WAF1, a potential mediator of p53 tumor suppression. Cell. 1993;75:817–25.PubMedCrossRef
138.
go back to reference el-Deiry WS, Tokino T, Waldman T, Oliner JD, Velculescu VE, Burrell M, et al. Topological control of p21WAF1/CIP1 expression in normal and neoplastic tissues. Cancer Res. 1995;55:2910–9.PubMed el-Deiry WS, Tokino T, Waldman T, Oliner JD, Velculescu VE, Burrell M, et al. Topological control of p21WAF1/CIP1 expression in normal and neoplastic tissues. Cancer Res. 1995;55:2910–9.PubMed
139.
go back to reference Agarwal S, Bell CM, Taylor SM, Moran RG. p53 Deletion or hotspot mutations enhance mTORC1 activity by altering lysosomal dynamics of TSC2 and Rheb. Mol Cancer Res. 2016;14:66–77.PubMedCrossRef Agarwal S, Bell CM, Taylor SM, Moran RG. p53 Deletion or hotspot mutations enhance mTORC1 activity by altering lysosomal dynamics of TSC2 and Rheb. Mol Cancer Res. 2016;14:66–77.PubMedCrossRef
140.
go back to reference Downie MM, Sanders DA, Maier LM, Stock DM, Kealey T. Peroxisome proliferator-activated receptor and farnesoid X receptor ligands differentially regulate sebaceous differentiation in human sebaceous gland organ cultures in vitro. Br J Dermatol. 2004;151:766–75.PubMedCrossRef Downie MM, Sanders DA, Maier LM, Stock DM, Kealey T. Peroxisome proliferator-activated receptor and farnesoid X receptor ligands differentially regulate sebaceous differentiation in human sebaceous gland organ cultures in vitro. Br J Dermatol. 2004;151:766–75.PubMedCrossRef
141.
go back to reference Trivedi NR, Cong Z, Nelson AM, Albert AJ, Rosamilia LL, Sivarajah S, et al. Peroxisome proliferator-activated receptors increase human sebum production. J Invest Dermatol. 2006;126:2002–9.PubMedCrossRef Trivedi NR, Cong Z, Nelson AM, Albert AJ, Rosamilia LL, Sivarajah S, et al. Peroxisome proliferator-activated receptors increase human sebum production. J Invest Dermatol. 2006;126:2002–9.PubMedCrossRef
142.
go back to reference Dozsa A, Dezso B, Toth BI, Bacsi A, Poliska S, Camera E, et al. PPARγ- mediated and arachidonic acid-dependent signaling is involved in differentiation and lipid production of human sebocytes. J Invest Dermatol. 2014;134:910–20.PubMedCrossRef Dozsa A, Dezso B, Toth BI, Bacsi A, Poliska S, Camera E, et al. PPARγ- mediated and arachidonic acid-dependent signaling is involved in differentiation and lipid production of human sebocytes. J Invest Dermatol. 2014;134:910–20.PubMedCrossRef
143.
go back to reference Schedlich LJ, Graham LD, O’Han MK, Muthukaruppan A, Yan X, Firth SM, et al. Molecular basis of the interaction between IGFBP-3 and retinoid X receptor: role in modulation of RAR-signaling. Arch Biochem Biophys. 2007;465:359–69.PubMedCrossRef Schedlich LJ, Graham LD, O’Han MK, Muthukaruppan A, Yan X, Firth SM, et al. Molecular basis of the interaction between IGFBP-3 and retinoid X receptor: role in modulation of RAR-signaling. Arch Biochem Biophys. 2007;465:359–69.PubMedCrossRef
145.
go back to reference Liu B, Lee HY, Weinzimer SA, Powell DR, Clifford JL, Kurie JM, et al. Direct functional interactions between insulin-like growth factor-binding protein-3 and retinoid X receptor-alpha regulate transcriptional signaling and apoptosis. J Biol Chem. 2000;275:33607–13.PubMedCrossRef Liu B, Lee HY, Weinzimer SA, Powell DR, Clifford JL, Kurie JM, et al. Direct functional interactions between insulin-like growth factor-binding protein-3 and retinoid X receptor-alpha regulate transcriptional signaling and apoptosis. J Biol Chem. 2000;275:33607–13.PubMedCrossRef
146.
go back to reference Lee KW, Ma L, Yan X, Liu B, Zhang XK, Cohen P. Rapid apoptosis induction by IGFBP-3 involves an insulin-like growth factor-independent nucleomitochondrial translocation of RXRalpha/Nur77. J Biol Chem. 2005;280:16942–8.PubMedCrossRef Lee KW, Ma L, Yan X, Liu B, Zhang XK, Cohen P. Rapid apoptosis induction by IGFBP-3 involves an insulin-like growth factor-independent nucleomitochondrial translocation of RXRalpha/Nur77. J Biol Chem. 2005;280:16942–8.PubMedCrossRef
147.
go back to reference Chan SS, Schedlich LJ, Twigg SM, Baxter RC. Inhibition of adipocyte differentiation by insulin-like growth factor-binding protein-3. Am J Physiol Endocrinol Metab. 2009;296:E654–63.PubMedCrossRef Chan SS, Schedlich LJ, Twigg SM, Baxter RC. Inhibition of adipocyte differentiation by insulin-like growth factor-binding protein-3. Am J Physiol Endocrinol Metab. 2009;296:E654–63.PubMedCrossRef
148.
go back to reference Buckbinder L, Talbott R, Velasco-Miguel S, Takenaka I, Faha B, Seizinger BR, et al. Induction of the growth inhibitor IGF-binding protein 3 by p53. Nature. 1995;377:646–9.PubMedCrossRef Buckbinder L, Talbott R, Velasco-Miguel S, Takenaka I, Faha B, Seizinger BR, et al. Induction of the growth inhibitor IGF-binding protein 3 by p53. Nature. 1995;377:646–9.PubMedCrossRef
149.
go back to reference Melnik BC. Apoptosis may explain the pharmacological mode of action and adverse effects of isotretinoin, including teratogenicity. Acta Derm Venereol. 2017;97:173–81.PubMedCrossRef Melnik BC. Apoptosis may explain the pharmacological mode of action and adverse effects of isotretinoin, including teratogenicity. Acta Derm Venereol. 2017;97:173–81.PubMedCrossRef
150.
go back to reference Van Nostrand JL, Brady CA, Jung H, Fuentes DR, Kozak MM, Johnson TM, et al. Inappropriate p53 activation during development induces features of CHARGE syndrome. Nature. 2014;514:228–32.PubMedPubMedCentral Van Nostrand JL, Brady CA, Jung H, Fuentes DR, Kozak MM, Johnson TM, et al. Inappropriate p53 activation during development induces features of CHARGE syndrome. Nature. 2014;514:228–32.PubMedPubMedCentral
151.
152.
go back to reference Franks S, Layton A, Glasier A. Cyproterone acetate/ethinyl estradiol for acne and hirsutism: time to revise prescribing policy. Hum Reprod. 2008;23:231–2.PubMedCrossRef Franks S, Layton A, Glasier A. Cyproterone acetate/ethinyl estradiol for acne and hirsutism: time to revise prescribing policy. Hum Reprod. 2008;23:231–2.PubMedCrossRef
153.
go back to reference Hassoun LA, Chahal DS, Sivamani RK, Larsen LN. The use of hormonal agents in the treatment of acne. Semin Cutan Med Surg. 2016;35:68–73.PubMedCrossRef Hassoun LA, Chahal DS, Sivamani RK, Larsen LN. The use of hormonal agents in the treatment of acne. Semin Cutan Med Surg. 2016;35:68–73.PubMedCrossRef
154.
go back to reference Inoue T, Miki Y, Kakuo S, Hachiya A, Kitahara T, Aiba S, et al. Expression of steroidogenic enzymes in human sebaceous glands. J Endocrinol. 2014;222:301–12.PubMedCrossRef Inoue T, Miki Y, Kakuo S, Hachiya A, Kitahara T, Aiba S, et al. Expression of steroidogenic enzymes in human sebaceous glands. J Endocrinol. 2014;222:301–12.PubMedCrossRef
155.
go back to reference Fan W, Yanase T, Morinaga H, Okabe T, Nomura M, Daitoku H, et al. Insulin- like growth factor 1/insulin signaling activates androgen signaling through direct interactions of Foxo1 with androgen receptor. J Biol Chem. 2007;282:7329–38.PubMedCrossRef Fan W, Yanase T, Morinaga H, Okabe T, Nomura M, Daitoku H, et al. Insulin- like growth factor 1/insulin signaling activates androgen signaling through direct interactions of Foxo1 with androgen receptor. J Biol Chem. 2007;282:7329–38.PubMedCrossRef
156.
go back to reference Pappas K, Xu J, Zairis S, Resnick-Silverman L, Abate F, Steinbach N, et al. p53 maintains baseline expression of multiple tumor suppressor genes. Mol Cancer Res. 2017;15:1051–62.PubMedCrossRef Pappas K, Xu J, Zairis S, Resnick-Silverman L, Abate F, Steinbach N, et al. p53 maintains baseline expression of multiple tumor suppressor genes. Mol Cancer Res. 2017;15:1051–62.PubMedCrossRef
157.
go back to reference Azmahani A, Nakamura Y, McNamara KM, Sasano H. The role of androgen under normal and pathological conditions in sebaceous glands: the possibility of target therapy. Curr Mol Pharmacol. 2016;9:311–9.PubMedCrossRef Azmahani A, Nakamura Y, McNamara KM, Sasano H. The role of androgen under normal and pathological conditions in sebaceous glands: the possibility of target therapy. Curr Mol Pharmacol. 2016;9:311–9.PubMedCrossRef
158.
go back to reference Barrault C, Garnier J, Pedretti N, Cordier-Dirikoc S, Ratineau E, Deguercy A, et al. Androgens induce sebaceous differentiation in sebocyte cells expressing a stable functional androgen receptor. J Steroid Biochem Mol Biol. 2015;152:34–44.PubMedCrossRef Barrault C, Garnier J, Pedretti N, Cordier-Dirikoc S, Ratineau E, Deguercy A, et al. Androgens induce sebaceous differentiation in sebocyte cells expressing a stable functional androgen receptor. J Steroid Biochem Mol Biol. 2015;152:34–44.PubMedCrossRef
159.
go back to reference Shenk JL, Fisher CJ, Chen SY, Zhou XF, Tillman K, Shemshedini L. p53 represses androgen-induced transactivation of prostate-specific antigen by disrupting hAR amino- to carboxyl-terminal interaction. J Biol Chem. 2001;276:38472–9.PubMedCrossRef Shenk JL, Fisher CJ, Chen SY, Zhou XF, Tillman K, Shemshedini L. p53 represses androgen-induced transactivation of prostate-specific antigen by disrupting hAR amino- to carboxyl-terminal interaction. J Biol Chem. 2001;276:38472–9.PubMedCrossRef
160.
go back to reference Alimirah F, Panchanathan R, Chen J, Zhang X, Ho SM, Choubey D. Expression of androgen receptor is negatively regulated by p53. Neoplasia. 2007;9:1152–9.PubMedPubMedCentralCrossRef Alimirah F, Panchanathan R, Chen J, Zhang X, Ho SM, Choubey D. Expression of androgen receptor is negatively regulated by p53. Neoplasia. 2007;9:1152–9.PubMedPubMedCentralCrossRef
161.
go back to reference Arnold I, Watt FM. c-Myc activation in transgenic mouse epidermis results in mobilization of stem cells and differentiation of their progeny. Curr Biol. 2001;11:558–68.PubMedCrossRef Arnold I, Watt FM. c-Myc activation in transgenic mouse epidermis results in mobilization of stem cells and differentiation of their progeny. Curr Biol. 2001;11:558–68.PubMedCrossRef
162.
go back to reference Lo Celso C, Berta MA, Braun KM, Frye M, Lyle S, Zouboulis CC, et al. Characterization of bipotential epidermal progenitors derived from human sebaceous gland: contrasting roles of c-Myc and beta-catenin. Stem Cells. 2008;26:1241–52.PubMedCrossRef Lo Celso C, Berta MA, Braun KM, Frye M, Lyle S, Zouboulis CC, et al. Characterization of bipotential epidermal progenitors derived from human sebaceous gland: contrasting roles of c-Myc and beta-catenin. Stem Cells. 2008;26:1241–52.PubMedCrossRef
163.
go back to reference Ceballos E, Delgado MD, Gutierrez P, Richard C, Müller D, Eilers M, et al. c-Myc antagonizes the effect of p53 on apoptosis and p21WAF1 transactivation in K562 leukemia cells. Oncogene. 2000;19:2194–204.PubMedCrossRef Ceballos E, Delgado MD, Gutierrez P, Richard C, Müller D, Eilers M, et al. c-Myc antagonizes the effect of p53 on apoptosis and p21WAF1 transactivation in K562 leukemia cells. Oncogene. 2000;19:2194–204.PubMedCrossRef
164.
go back to reference Cottle DL, Kretzschmar K, Schweiger PJ, Quist SR, Gollnick HP, Natsuga K, et al. c-MYC-induced sebaceous gland differentiation is controlled by an androgen receptor/p53 axis. Cell Rep. 2013;3:427–41.PubMedPubMedCentralCrossRef Cottle DL, Kretzschmar K, Schweiger PJ, Quist SR, Gollnick HP, Natsuga K, et al. c-MYC-induced sebaceous gland differentiation is controlled by an androgen receptor/p53 axis. Cell Rep. 2013;3:427–41.PubMedPubMedCentralCrossRef
166.
go back to reference Shi XB, Xue L, Yang J, Ma AH, Zhao J, Xu M, et al. An androgen-regulated miRNA suppresses Bak1 expression and induces androgen-independent growth of prostate cancer cells. Proc Natl Acad Sci USA. 2007;104:19983–8.PubMedPubMedCentralCrossRef Shi XB, Xue L, Yang J, Ma AH, Zhao J, Xu M, et al. An androgen-regulated miRNA suppresses Bak1 expression and induces androgen-independent growth of prostate cancer cells. Proc Natl Acad Sci USA. 2007;104:19983–8.PubMedPubMedCentralCrossRef
167.
go back to reference Sen A, Prizant H, Light A, Biswas A, Hayes E, Lee HJ, et al. Androgens regulate ovarian follicular development by increasing follicle stimulating hormone receptor and microRNA-125b expression. Proc Natl Acad Sci USA. 2014;111:3008–13.PubMedPubMedCentralCrossRef Sen A, Prizant H, Light A, Biswas A, Hayes E, Lee HJ, et al. Androgens regulate ovarian follicular development by increasing follicle stimulating hormone receptor and microRNA-125b expression. Proc Natl Acad Sci USA. 2014;111:3008–13.PubMedPubMedCentralCrossRef
168.
169.
go back to reference Le MT, Shyh-Chang N, Khaw SL, Chin L, Teh C, Tay J, et al. Conserved regulation of p53 network dosage by microRNA-125b occurs through evolving miRNA-target gene pairs. PLoS Genet. 2011;7:e1002242.PubMedPubMedCentralCrossRef Le MT, Shyh-Chang N, Khaw SL, Chin L, Teh C, Tay J, et al. Conserved regulation of p53 network dosage by microRNA-125b occurs through evolving miRNA-target gene pairs. PLoS Genet. 2011;7:e1002242.PubMedPubMedCentralCrossRef
170.
171.
go back to reference Chen L, Wolff DW, Xie Y, Lin MF, Tu Y. Cyproterone acetate enhances TRAIL-induced androgen-independent prostate cancer cell apoptosis via up- regulation of death receptor 5. BMC Cancer. 2017;17:179.PubMedPubMedCentralCrossRef Chen L, Wolff DW, Xie Y, Lin MF, Tu Y. Cyproterone acetate enhances TRAIL-induced androgen-independent prostate cancer cell apoptosis via up- regulation of death receptor 5. BMC Cancer. 2017;17:179.PubMedPubMedCentralCrossRef
172.
go back to reference Boudou P, Soliman H, Chivot M, Villette JM, Vexiau P, Belanger A, et al. Effect of oral isotretinoin treatment on skin androgen receptor levels in male acneic patients. J Clin Endocrinol Metab. 1995;80:1158–61.PubMed Boudou P, Soliman H, Chivot M, Villette JM, Vexiau P, Belanger A, et al. Effect of oral isotretinoin treatment on skin androgen receptor levels in male acneic patients. J Clin Endocrinol Metab. 1995;80:1158–61.PubMed
173.
go back to reference Kretzschmar K, Cottle DL, Donati G, Chiang MF, Quist SR, Gollnick HP, et al. BLIMP1 is required for postnatal epidermal homeostasis but does not define a sebaceous gland progenitor under steady-state conditions. Stem Cell Rep. 2014;3:620–33.CrossRef Kretzschmar K, Cottle DL, Donati G, Chiang MF, Quist SR, Gollnick HP, et al. BLIMP1 is required for postnatal epidermal homeostasis but does not define a sebaceous gland progenitor under steady-state conditions. Stem Cell Rep. 2014;3:620–33.CrossRef
174.
go back to reference Yan J, Jiang J, Lim CA, Wu Q, Ng HH, Chin KC. BLIMP1 regulates cell growth through repression of p53 transcription. Proc Natl Acad Sci USA. 2007;104:1841–6.PubMedPubMedCentralCrossRef Yan J, Jiang J, Lim CA, Wu Q, Ng HH, Chin KC. BLIMP1 regulates cell growth through repression of p53 transcription. Proc Natl Acad Sci USA. 2007;104:1841–6.PubMedPubMedCentralCrossRef
175.
go back to reference Horsley V, O’Carroll D, Tooze R, Ohinata Y, Saitou M, Obukhanych T, et al. Blimp1 defines a progenitor population that governs cellular input to the sebaceous gland. Cell. 2006;126:597–609.PubMedPubMedCentralCrossRef Horsley V, O’Carroll D, Tooze R, Ohinata Y, Saitou M, Obukhanych T, et al. Blimp1 defines a progenitor population that governs cellular input to the sebaceous gland. Cell. 2006;126:597–609.PubMedPubMedCentralCrossRef
176.
go back to reference Zouboulis C, Seltmann H, Neitzel H, Orfanos C. Establishment and characterization of an immortalized human sebaceous gland cell line. J Invest Dermatol. 1999;113:1011–20.PubMedCrossRef Zouboulis C, Seltmann H, Neitzel H, Orfanos C. Establishment and characterization of an immortalized human sebaceous gland cell line. J Invest Dermatol. 1999;113:1011–20.PubMedCrossRef
177.
go back to reference Thiboutot D, Jabara S, McAllister JM, Sivarajah A, Gilliland K, Cong Z, et al. Human skin is a steroidogenic tissue: steroidogenic enzymes and cofactors are expressed in epidermis, normal sebocytes, and an immortalized sebocyte cell line (SEB-1). J Invest Dermatol. 2003;120:905–14.PubMedCrossRef Thiboutot D, Jabara S, McAllister JM, Sivarajah A, Gilliland K, Cong Z, et al. Human skin is a steroidogenic tissue: steroidogenic enzymes and cofactors are expressed in epidermis, normal sebocytes, and an immortalized sebocyte cell line (SEB-1). J Invest Dermatol. 2003;120:905–14.PubMedCrossRef
178.
go back to reference Barrault C, Dichamp I, Garnier J, Pedretti N, Juchaux F, Deguercy A, et al. Immortalized sebocytes can spontaneously differentiate into a sebaceous-like phenotype when cultured as a 3D epithelium. Exp Dermatol. 2012;21:314–6.PubMedCrossRef Barrault C, Dichamp I, Garnier J, Pedretti N, Juchaux F, Deguercy A, et al. Immortalized sebocytes can spontaneously differentiate into a sebaceous-like phenotype when cultured as a 3D epithelium. Exp Dermatol. 2012;21:314–6.PubMedCrossRef
179.
go back to reference Zouboulis CC, Xia L, Akamatsu H, Seltmann H, Fritsch M, Hornemann S, et al. The human sebocyte culture model provides new insights into development and management of seborrhoea and acne. Dermatology. 1998;196:21–31.PubMedCrossRef Zouboulis CC, Xia L, Akamatsu H, Seltmann H, Fritsch M, Hornemann S, et al. The human sebocyte culture model provides new insights into development and management of seborrhoea and acne. Dermatology. 1998;196:21–31.PubMedCrossRef
181.
go back to reference Jha KK, Banga S, Palejwala V, Ozer HL. SV40-mediated immortalization. Exp Cell Res. 1998;245:1–7.PubMedCrossRef Jha KK, Banga S, Palejwala V, Ozer HL. SV40-mediated immortalization. Exp Cell Res. 1998;245:1–7.PubMedCrossRef
182.
go back to reference McCormick F, Clark R, Harlow E, Tjian R. SV40 T antigen binds specifically to a cellular 53 K protein in vitro. Nature. 1981;292:63–5.PubMedCrossRef McCormick F, Clark R, Harlow E, Tjian R. SV40 T antigen binds specifically to a cellular 53 K protein in vitro. Nature. 1981;292:63–5.PubMedCrossRef
183.
go back to reference Dobbelstein M, Roth J. The large T antigen of simian virus 40 binds and inactivates p53 but not p73. J Gen Virol. 1998;79:3079–83.PubMedCrossRef Dobbelstein M, Roth J. The large T antigen of simian virus 40 binds and inactivates p53 but not p73. J Gen Virol. 1998;79:3079–83.PubMedCrossRef
184.
go back to reference Jiang D, Srinivasan A, Lozano G, Robbins PD. SV40 T antigen abrogates p53-mediated transcriptional activity. Oncogene. 1993;8:2805–12.PubMed Jiang D, Srinivasan A, Lozano G, Robbins PD. SV40 T antigen abrogates p53-mediated transcriptional activity. Oncogene. 1993;8:2805–12.PubMed
185.
go back to reference Lazo PA, Santos CR. Interference with p53 functions in human viral infections, a target for novel antiviral strategies? Rev Med Virol. 2011;21:285–300.PubMed Lazo PA, Santos CR. Interference with p53 functions in human viral infections, a target for novel antiviral strategies? Rev Med Virol. 2011;21:285–300.PubMed
186.
go back to reference Wróbel A, Seltmann H, Fimmel S, Müller-Decker K, Tsukada M, Bogdanoff B, et al. Differentiation and apoptosis in human immortalized sebocytes. J Invest Dermatol. 2003;120:175–81.PubMedCrossRef Wróbel A, Seltmann H, Fimmel S, Müller-Decker K, Tsukada M, Bogdanoff B, et al. Differentiation and apoptosis in human immortalized sebocytes. J Invest Dermatol. 2003;120:175–81.PubMedCrossRef
187.
go back to reference Guruvayoorappan C, Pradeep CR, Kuttan G. 13-cis-retinoic acid induces apoptosis by modulating caspase-3, bcl-2, and p53 gene expression and regulates the activation of transcription factors in B16F-10 melanoma cells. J Environ Pathol Toxicol Oncol. 2008;27:197–207.PubMedCrossRef Guruvayoorappan C, Pradeep CR, Kuttan G. 13-cis-retinoic acid induces apoptosis by modulating caspase-3, bcl-2, and p53 gene expression and regulates the activation of transcription factors in B16F-10 melanoma cells. J Environ Pathol Toxicol Oncol. 2008;27:197–207.PubMedCrossRef
188.
go back to reference Melnik BC, Schmitz G. Are therapeutic effects of antiacne agents mediated by activation of FoxO1 and inhibition of mTORC1? Exp Dermatol. 2013;22:502–4.PubMedPubMedCentralCrossRef Melnik BC, Schmitz G. Are therapeutic effects of antiacne agents mediated by activation of FoxO1 and inhibition of mTORC1? Exp Dermatol. 2013;22:502–4.PubMedPubMedCentralCrossRef
189.
go back to reference Toledo F, Wahl GM. Regulating the p53 pathway: in vitro hypotheses, in vivo veritas. Nat Rev Cancer. 2006;6:909–23.PubMedCrossRef Toledo F, Wahl GM. Regulating the p53 pathway: in vitro hypotheses, in vivo veritas. Nat Rev Cancer. 2006;6:909–23.PubMedCrossRef
190.
go back to reference Lazo PA. Reverting p53 activation after recovery of cellular stress to resume with cell cycle progression. Cell Signal. 2017;33:49–58.PubMedCrossRef Lazo PA. Reverting p53 activation after recovery of cellular stress to resume with cell cycle progression. Cell Signal. 2017;33:49–58.PubMedCrossRef
191.
go back to reference Fu W, Ma Q, Chen L, Li P, Zhang M, Ramamoorthy S, et al. MDM2 acts downstream of p53 as an E3 ligase to promote FOXO ubiquitination and degradation. J Biol Chem. 2009;284:13987–4000.PubMedPubMedCentralCrossRef Fu W, Ma Q, Chen L, Li P, Zhang M, Ramamoorthy S, et al. MDM2 acts downstream of p53 as an E3 ligase to promote FOXO ubiquitination and degradation. J Biol Chem. 2009;284:13987–4000.PubMedPubMedCentralCrossRef
192.
go back to reference Melnik BC. Pro-inflammatory sebocyte growth and survival signalling in acne vulgaris are reversed by pro-apoptotic isotretinoin signalling. Exp Dermatol. 2016;25:676–7.PubMedCrossRef Melnik BC. Pro-inflammatory sebocyte growth and survival signalling in acne vulgaris are reversed by pro-apoptotic isotretinoin signalling. Exp Dermatol. 2016;25:676–7.PubMedCrossRef
193.
go back to reference Melnik BC. The TRAIL to acne pathogenesis: let’s focus on death pathways. Exp Dermatol. 2017;26:270–2.PubMedCrossRef Melnik BC. The TRAIL to acne pathogenesis: let’s focus on death pathways. Exp Dermatol. 2017;26:270–2.PubMedCrossRef
Metadata
Title
p53: key conductor of all anti-acne therapies
Author
Bodo C. Melnik
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2017
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-017-1297-2

Other articles of this Issue 1/2017

Journal of Translational Medicine 1/2017 Go to the issue