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Published in: Strahlentherapie und Onkologie 1/2014

01-01-2014 | Original article

The effect of resveratrol in combination with irradiation and chemotherapy

Study using Merkel cell carcinoma cell lines

Authors: G. Heiduschka, C. Lill, R. Seemann, M. Brunner, R. Schmid, R. Houben, J. Bigenzahn, D. Thurnher, M.D.

Published in: Strahlentherapie und Onkologie | Issue 1/2014

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Abstract

Background and purpose

Merkel cell carcinoma (MCC) is a rare, but highly malignant tumor of the skin. In case of systemic disease, possible therapeutic options include irradiation or chemotherapy. The aim of this study was to evaluate whether the flavonoid resveratrol enhances the effect of radiotherapy or chemotherapy in MCC cell lines.

Materials and methods

The two MCC cell lines MCC13 and MCC26 were treated with increasing doses of resveratrol. Combination experiments were conducted with cisplatin and etoposide. Colony forming assays were performed after sequential irradiation with 1, 2, 3, 4, 6, and 8 Gy and apoptosis was assessed with flow cytometry. Expression of cancer drug targets was analyzed by real-time PCR array.

Results

Resveratrol is cytotoxic in MCC cell lines. Cell growth is inhibited by induction of apoptosis. The combination with cisplatin and etoposide resulted in a partially synergistic inhibition of cell proliferation. Resveratrol and irradiation led to a synergistic reduction in colony formation compared to irradiation alone. Evaluation of gene expression did not show significant difference between the cell lines.

Conclusion

Due to its radiosensitizing effect, resveratrol seems to be a promising agent in combination with radiation therapy. The amount of chemosensitizing depends on the cell lines tested.
Literature
1.
go back to reference Becker JC (2010) Merkel cell carcinoma. Ann Oncol 21(Suppl 7):vii81–vii85PubMed Becker JC (2010) Merkel cell carcinoma. Ann Oncol 21(Suppl 7):vii81–vii85PubMed
3.
go back to reference Bickle K, Glass LF, Messina JL et al (2004) Merkel cell carcinoma: a clinical, histopathologic, and immunohistochemical review. Semin Cutan Med Surg 23(1):46–53PubMedCrossRef Bickle K, Glass LF, Messina JL et al (2004) Merkel cell carcinoma: a clinical, histopathologic, and immunohistochemical review. Semin Cutan Med Surg 23(1):46–53PubMedCrossRef
4.
go back to reference Poulsen M (2005) Merkel cell carcinoma of skin: diagnosis and management strategies. Drugs Aging 22(3):219–229PubMedCrossRef Poulsen M (2005) Merkel cell carcinoma of skin: diagnosis and management strategies. Drugs Aging 22(3):219–229PubMedCrossRef
5.
go back to reference Albores-Saavedra J, Batich K, Chable-Montero F et al (2010) Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population based study. J Cutan Pathol 37(1):20–27PubMedCrossRef Albores-Saavedra J, Batich K, Chable-Montero F et al (2010) Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population based study. J Cutan Pathol 37(1):20–27PubMedCrossRef
6.
go back to reference Calder KB, Smoller BR (2010) New insights into Merkel cell carcinoma. Adv Anat Pathol 17(3):155–161PubMedCrossRef Calder KB, Smoller BR (2010) New insights into Merkel cell carcinoma. Adv Anat Pathol 17(3):155–161PubMedCrossRef
7.
go back to reference Bischof M, Kampen M van, Huber P, Wannenmacher M (1999) Merkel cell carcinoma: the role of radiation therapy in general management. Strahlenther Onkol 175(12):611–615PubMedCrossRef Bischof M, Kampen M van, Huber P, Wannenmacher M (1999) Merkel cell carcinoma: the role of radiation therapy in general management. Strahlenther Onkol 175(12):611–615PubMedCrossRef
8.
go back to reference Roeder F, Krempien R, Sterzing F et al (2007) Radiotherapy for localised and advanced Merkel cell carcinoma of the skin: a single institution case series. Eur J Dermatol 17(3):229–233PubMed Roeder F, Krempien R, Sterzing F et al (2007) Radiotherapy for localised and advanced Merkel cell carcinoma of the skin: a single institution case series. Eur J Dermatol 17(3):229–233PubMed
9.
go back to reference Dancey AL, Rayatt SS, Soon C et al (2006) Merkel cell carcinoma: a report of 34 cases and literature review. J Plast Reconstr Aesthet Surg 59(12):1294–1299PubMedCrossRef Dancey AL, Rayatt SS, Soon C et al (2006) Merkel cell carcinoma: a report of 34 cases and literature review. J Plast Reconstr Aesthet Surg 59(12):1294–1299PubMedCrossRef
10.
go back to reference Sas-Korczyńska B, Korzeniowski S, Wójcik E (2010) Comparison of the effectiveness of “late” and “early” prophylactic cranial irradiation in patients with limited-stage small cell lung cancer. Strahlenther Onkol 186(6):315–319PubMedCrossRef Sas-Korczyńska B, Korzeniowski S, Wójcik E (2010) Comparison of the effectiveness of “late” and “early” prophylactic cranial irradiation in patients with limited-stage small cell lung cancer. Strahlenther Onkol 186(6):315–319PubMedCrossRef
11.
go back to reference Baumgart T, Klautke G, Kriesen S et al (2012) Radiosensitizing effect of epothilone B on human epithelial cancer cells. Strahlenther Onkol 188(2):177–184PubMedCrossRef Baumgart T, Klautke G, Kriesen S et al (2012) Radiosensitizing effect of epothilone B on human epithelial cancer cells. Strahlenther Onkol 188(2):177–184PubMedCrossRef
12.
go back to reference Stingl L, Niewidok N, Müller N et al (2012) Radiosensitizing effect of the novel Hsp90 inhibitor NVP-AUY922 in human tumour cell lines silenced for Hsp90α. Strahlenther Onkol 188(6):507–515PubMedCrossRef Stingl L, Niewidok N, Müller N et al (2012) Radiosensitizing effect of the novel Hsp90 inhibitor NVP-AUY922 in human tumour cell lines silenced for Hsp90α. Strahlenther Onkol 188(6):507–515PubMedCrossRef
13.
go back to reference Kotowski U, Heiduschka G, Brunner M et al (2011) Radiosensitization of head and neck cancer cells by the phytochemical agent sulforaphane. Strahlenther Onkol 187(9):575–580PubMedCrossRef Kotowski U, Heiduschka G, Brunner M et al (2011) Radiosensitization of head and neck cancer cells by the phytochemical agent sulforaphane. Strahlenther Onkol 187(9):575–580PubMedCrossRef
14.
go back to reference Takagi M, Sakata K, Someya M et al (2012) The combination of hyperthermia or chemotherapy with gimeracil for effective radiosensitization. Strahlenther Onkol 188(3):255–261PubMedCrossRef Takagi M, Sakata K, Someya M et al (2012) The combination of hyperthermia or chemotherapy with gimeracil for effective radiosensitization. Strahlenther Onkol 188(3):255–261PubMedCrossRef
15.
go back to reference Johnson GE, Ivanov VN, Hei TK (2008) Radiosensitization of melanoma cells through combined inhibition of protein regulators of cell survival. Apoptosis 13(6):790–802PubMedCrossRef Johnson GE, Ivanov VN, Hei TK (2008) Radiosensitization of melanoma cells through combined inhibition of protein regulators of cell survival. Apoptosis 13(6):790–802PubMedCrossRef
16.
go back to reference Aluyen JK, Ton QN, Tran T et al (2012) Resveratrol: potential as anticancer agent. J Diet Suppl 9(1):45–56PubMedCrossRef Aluyen JK, Ton QN, Tran T et al (2012) Resveratrol: potential as anticancer agent. J Diet Suppl 9(1):45–56PubMedCrossRef
17.
go back to reference Knutson MD, Leeuwenburgh C (2008) Resveratrol and novel potent activators of SIRT1: effects on aging and age-related diseases. Nutr Rev 66(10):591–596PubMedCrossRef Knutson MD, Leeuwenburgh C (2008) Resveratrol and novel potent activators of SIRT1: effects on aging and age-related diseases. Nutr Rev 66(10):591–596PubMedCrossRef
18.
go back to reference Vang O, Ahmad N, Baile CA et al (2011) What is new for an old molecule? Systematic review and recommendations on the use of resveratrol. PLoS One 6(6):e19881PubMedCentralPubMedCrossRef Vang O, Ahmad N, Baile CA et al (2011) What is new for an old molecule? Systematic review and recommendations on the use of resveratrol. PLoS One 6(6):e19881PubMedCentralPubMedCrossRef
19.
go back to reference Heiduschka G, Erovic BM, Vormittag L et al (2009) 7beta-hydroxycholesterol induces apoptosis and regulates cyclooxygenase 2 in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 135(3):261–267PubMedCrossRef Heiduschka G, Erovic BM, Vormittag L et al (2009) 7beta-hydroxycholesterol induces apoptosis and regulates cyclooxygenase 2 in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 135(3):261–267PubMedCrossRef
20.
go back to reference Chou TC, Talalay P (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 22:27–55PubMedCrossRef Chou TC, Talalay P (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 22:27–55PubMedCrossRef
21.
go back to reference Franken NAP, Rodermond HM, Stap J et al (2006) Clonogenic assay of cells in vitro. Nat Protoc 1(5):2315–2319PubMedCrossRef Franken NAP, Rodermond HM, Stap J et al (2006) Clonogenic assay of cells in vitro. Nat Protoc 1(5):2315–2319PubMedCrossRef
22.
go back to reference Eder-Czembirek C, Erovic BM, Czembirek C et al (2010) Betulinic acid a radiosensitizer in head and neck squamous cell carcinoma cell lines. Strahlenther Onkol 186(3):143–148PubMedCrossRef Eder-Czembirek C, Erovic BM, Czembirek C et al (2010) Betulinic acid a radiosensitizer in head and neck squamous cell carcinoma cell lines. Strahlenther Onkol 186(3):143–148PubMedCrossRef
23.
go back to reference R Development Core Team 2 (2013) R: a language and environment for statistical computing. Vienna(Austria):ISBN3-900051-07-0-URLhttp:-www.R- project.org R Development Core Team 2 (2013) R: a language and environment for statistical computing. Vienna(Austria):ISBN3-900051-07-0-URLhttp:-www.R- project.org
24.
go back to reference Fournier DA, Skaug HJ, Ancheta J, Ianelli J (2012) AD Model Builder: using automatic differentiation for statistical inference of highly parameterized complex nonlinear models. Optim Method … Fournier DA, Skaug HJ, Ancheta J, Ianelli J (2012) AD Model Builder: using automatic differentiation for statistical inference of highly parameterized complex nonlinear models. Optim Method …
25.
go back to reference Skaug HJ, Fournier DA, Nielsen A et al (o J) Generalized linear mixed models using ad model builder. version 0.7.2.12. URL http:r-forge.r-project.org/projects/glmmadmb/. Accessed 01 Oct 2013 Skaug HJ, Fournier DA, Nielsen A et al (o J) Generalized linear mixed models using ad model builder. version 0.7.2.12. URL http:r-forge.r-project.org/projects/glmmadmb/. Accessed 01 Oct 2013
26.
go back to reference Duprat JP, Landman G, Salvajoli JV, Brechtbühl ER (2011) A review of the epidemiology and treatment of Merkel cell carcinoma. Clinics 66(10):1817–1823PubMedCentralPubMedCrossRef Duprat JP, Landman G, Salvajoli JV, Brechtbühl ER (2011) A review of the epidemiology and treatment of Merkel cell carcinoma. Clinics 66(10):1817–1823PubMedCentralPubMedCrossRef
27.
go back to reference Vergara D, Simeone P, Toraldo D et al (2012) Resveratrol downregulates Akt/GSK and ERK signalling pathways in OVCAR-3 ovarian cancer cells. Mol Biosyst 8(4):1078–1087PubMedCrossRef Vergara D, Simeone P, Toraldo D et al (2012) Resveratrol downregulates Akt/GSK and ERK signalling pathways in OVCAR-3 ovarian cancer cells. Mol Biosyst 8(4):1078–1087PubMedCrossRef
28.
go back to reference Miki H, Uehara N, Kimura A et al (2012) Resveratrol induces apoptosis via ROS-triggered autophagy in human colon cancer cells. Int J Oncol 40(4):1020–1028PubMedCentralPubMed Miki H, Uehara N, Kimura A et al (2012) Resveratrol induces apoptosis via ROS-triggered autophagy in human colon cancer cells. Int J Oncol 40(4):1020–1028PubMedCentralPubMed
29.
go back to reference Kartal M, Saydam G, Sahin F, Baran Y (2011) Resveratrol triggers apoptosis through regulating ceramide metabolizing genes in human K562 chronic myeloid leukemia cells. Nutr Cancer 63(4):637–644PubMedCrossRef Kartal M, Saydam G, Sahin F, Baran Y (2011) Resveratrol triggers apoptosis through regulating ceramide metabolizing genes in human K562 chronic myeloid leukemia cells. Nutr Cancer 63(4):637–644PubMedCrossRef
30.
go back to reference Xie Y, Zhang J, Xu Y, Shao C (2012) SirT1 confers hypoxia-induced radioresistance via the modulation of c-Myc stabilization on hepatoma cells. J Radiat Res 53(1):44–50PubMedCrossRef Xie Y, Zhang J, Xu Y, Shao C (2012) SirT1 confers hypoxia-induced radioresistance via the modulation of c-Myc stabilization on hepatoma cells. J Radiat Res 53(1):44–50PubMedCrossRef
31.
go back to reference Casanova F, Quarti J, Costa DCF da et al (2012) Resveratrol chemosensitizes breast cancer cells to melphalan by cell cycle arrest. J Cell Biochem n/a–n/a Casanova F, Quarti J, Costa DCF da et al (2012) Resveratrol chemosensitizes breast cancer cells to melphalan by cell cycle arrest. J Cell Biochem n/a–n/a
32.
go back to reference Santandreu FM, Valle A, Oliver J, Roca P (2011) Resveratrol potentiates the cytotoxic oxidative stress induced by chemotherapy in human colon cancer cells. Cell Physiol Biochem 28(2):219–228PubMedCrossRef Santandreu FM, Valle A, Oliver J, Roca P (2011) Resveratrol potentiates the cytotoxic oxidative stress induced by chemotherapy in human colon cancer cells. Cell Physiol Biochem 28(2):219–228PubMedCrossRef
Metadata
Title
The effect of resveratrol in combination with irradiation and chemotherapy
Study using Merkel cell carcinoma cell lines
Authors
G. Heiduschka
C. Lill
R. Seemann
M. Brunner
R. Schmid
R. Houben
J. Bigenzahn
D. Thurnher, M.D.
Publication date
01-01-2014
Publisher
Springer Berlin Heidelberg
Published in
Strahlentherapie und Onkologie / Issue 1/2014
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-013-0445-8

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