Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

Effects of magnolol on UVB-induced skin cancer development in mice and its possible mechanism of action

Authors: Chandeshwari Chilampalli, Ruth Guillermo, Xiaoying Zhang, Radhey S Kaushik, Alan Young, David Zeman, Michael B Hildreth, Hesham Fahmy, Chandradhar Dwivedi

Published in: BMC Cancer | Issue 1/2011

Login to get access

Abstract

Background

Magnolol, a plant lignan isolated from the bark and seed cones of Magnolia officinalis, has been shown to have chemopreventive effects on chemically-induced skin cancer development. The objectives of this investigation are to study the anticarcinogenic effects of magnolol on UVB-induced skin tumor development in SKH-1 mice, a model relevant to humans, and determine the possible role of apoptosis and cell cycle arrest involved in the skin tumor development.

Methods

UVB-induced skin carcinogenesis model in SKH-1 mice was used for determining the preventive effects of magnolol on skin cancer development. Western blottings and flow cytometric analysis were used to study the effects of magnolol on apoptosis and cell cycle.

Results

Magnolol pretreated groups (30, 60 μ g) before UVB treatments (30 mJ/cm2, 5 days/week) resulted in 27-55% reduction in tumor multiplicity as compared to control group in SKH-1 mice. Magnolol pretreatment increased the cleavage of caspase-8 and poly-(-ADP-ribose) polymerase (PARP), increased the expression of p21, a cell cycle inhibitor, and decreased the expression of proteins involved in the G2/M phase of cell cycle in skin samples from SKH-1 mice.
Treatment of A431 cells with magnolol decreased cell viability and cell proliferation in a concentration dependent manner. Magnolol induced G2/M phase cell cycle arrest in A431 cells at 12 h with a decreased expression of cell cycle proteins such as cyclin B1, cyclin A, CDK4, Cdc2 and simultaneous increase in the expression of Cip/p21, a cyclin-dependent kinase inhibitor. Magnolol induced apoptosis in vivo and in vitro with an increased cleavage of caspase-8 and PARP. Phospho-signal transducers and activators of transcription 3 (Tyr705), B-Raf, p-MEK, and p-AKT were down-regulated, whereas phosphorylation of ERK was induced by magnolol in A431 cells.

Conclusions

Magnolol pretreatments prevent UVB-induced skin cancer development by enhancing apoptosis, causing cell cycle arrest at G2/M phase, and affecting various signaling pathways. Magnolol could be a potentially safe and potent anticarcinogenic agent against skin cancer.
Appendix
Available only for authorised users
Literature
1.
Rogers HW, Weinstock MA, Harris AR, Hinckley MR, Feldman SR, Fleischer AB, Coldiron BM: Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol. 2010, 146: 283-287. 10.1001/archdermatol.2010.19.CrossRefPubMed
2.
Siegel R, Ward E, Brawley O, Jemal A: Cancer Statistics, 2011. CA Cancer J Clin. 2011, 61: 212-236. 10.3322/caac.20121.CrossRefPubMed
3.
Kremer KH: Sunlight and skin cancer: Another link revealed. Proc Natl Acad Sci USA. 1997, 95: 11-14.CrossRef
4.
Lu YP, Lou YR, Yen P, Mitchell D, Huang MT, Conney AH: Time course for early adaptive responses to ultraviolet B light in the epidermis of SKH-1 mice. Cancer Res. 1999, 4591-4602.
5.
Katiyar SK, Korman NJ, Mukhtar H, Agarwal R: Protective effects of silymarin against photocarcinogenesis in a mouse skin model. J Natl Cancer Inst. 1997, 89: 556-566. 10.1093/jnci/89.8.556.CrossRefPubMed
6.
7.
Rigel DS, Friedman R, Kopf AW: Lifetime risk for development of skin cancer in the US population: Current estimate is now 1 in 5. J Am Acad Dermatol. 1996, 35: 1012-1013. 10.1016/S0190-9622(96)90139-5.CrossRefPubMed
8.
De Gruijil FR: Photocarcinogenesis: UVA vs UVB radiation. Skin Pharmacol Appl Skin Physiol. 2002, 15: 316-320. 10.1159/000064535.CrossRef
9.
Tyrell RM: Activation of mammalian gene expression by the UV component of sunlight-from models to reality. Bioessays. 1996, 18: 139-148. 10.1002/bies.950180210.CrossRef
10.
Pinnell SR: Cutaneous photodamage, oxidative stress and topical antioxidant protection. J Am Acad Dermatol. 2003, 48: 1-19. 10.1067/mjd.2003.16.CrossRefPubMed
11.
Wolf P, Donawho CK, Kripke ML: Effects of sunscreens on UV radiation-induced enhancement of melanoma growth in mice. J Natl cancer inst. 1994, 86: 99-105. 10.1093/jnci/86.2.99.CrossRefPubMed
12.
Dwivedi C, Maydew ER, Hora J, Ramaeker D, Guan X: Chemopreventive effects of various concentrations of alpha-santalol on skin cancer development in CD-1 mice. Eur J Cancer Prev. 2005, 14: 473-476. 10.1097/01.cej.0000178075.20124.2a.CrossRefPubMed
13.
Gu M, Singh RP, Dhanalakshmi S, Agarwal C, Agarwal R: Silibinin inhibits inflammatory and angiogenic attributes in photocarcinogenesis in SKH-1 hairless mice. Cancer Res. 2007, 67: 3483-3491. 10.1158/0008-5472.CAN-06-3955.CrossRefPubMed
14.
Surh YJ: Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer. 2003, 3: 768-780. 10.1038/nrc1189.CrossRefPubMed
15.
Won YK, Ong C, Shi X, Shen HM: Chemopreventive activity of parthenolide against UVB-induced skin cancer and its mechanisms. Carcinogenesis. 2004, 25: 1449-1458. 10.1093/carcin/bgh151.CrossRefPubMed
16.
Einspahr JG, Bowden GT, Alberts DS: Skin cancer chemoprevention: strategies to save our skin. Recent Results Cancer Res. 2003, 163: 151-164. 10.1007/978-3-642-55647-0_14. discussion 264-6CrossRefPubMed
17.
Chilampalli S, Zhang X, Fahmy H, Kaushik RS, Zeman D, Hildreth M, Dwivedi C: Chemopreventive effects of honokiol on UVB-induced skin cancer development. Anticancer Research. 2010, 30: 777-784.PubMed
18.
Fugita S, Taira J: Biphenyl compounds are hydroxyl radiacl scavengers: their effective inhibition for UV-induced mutation in salmonella tyhimurium TA 102. Free Radic Biol Med. 1994, 17: 273-277. 10.1016/0891-5849(94)90083-3.CrossRef
19.
Wang JP, HSU MF, Raung SL, Chen CC, Kuo JS, Teng CM: Anti- inflammatory and analgesic effects of magnolol. Naunyn Schmiedebergs Arch Pharmacol. 1992, 346: 707-712.CrossRefPubMed
20.
Maruyuma Y, Kuribara H, Morita M, Yuzurihara M, Weintraub ST: Identification of magnolol and honokiol as anxiolytic agents in extracts of saiboku-to, an oriental herbal medicine. J Na Prod. 1998, 61: 135-138. 10.1021/np9702446.CrossRef
21.
Konoshima T, Kozuka M, Tokuda H, Nishino H, Iwashima A, Haruna M, Ito K, Tanabe M: Studies on inhibitors of skin tumor promotion, IX. Neolignans from Magnolia officinalis. J Nat Prod. 1991, 54: 816-822. 10.1021/np50075a010.CrossRefPubMed
22.
Meeran SM, Katiyar SK: Cell cycle control as a basis for cancer chemoprevention through dietary agents. Front Biosci. 2008, 13: 2191-2202. 10.2741/2834.CrossRefPubMedPubMedCentral
23.
Cowan KJ, Storey KB: Mitogen activated protein kinases: new signaling pathways functioning in cellular responses to environmental stress and inflammation. J Exp Biol. 2003, 206: 1107-1115. 10.1242/jeb.00220.CrossRefPubMed
24.
Hua Y, Richard J: The STATs of cancer- new molecular targets of age. Nat Rev Cancer. 2004, 4: 97-105. 10.1038/nrc1275.CrossRef
25.
Bachelor MA, Bowden GT: UVA mediated activation of signaling pathways involved in skin tumor promotion and progression. Semin Cancer Biol. 2004, 14: 131-138. 10.1016/j.semcancer.2003.09.017.CrossRefPubMed
26.
Han M, Golden A, Han Y, Sternberg PC: C. elegans lin-45 raf gene participates in let-60 ras-stimulated vulval differentiation. Nature. 1993, 363: 133-139. 10.1038/363133a0.CrossRefPubMed
27.
Nishida Y, Hata M, Ayaki T: Proliferation of both somatic and germ cells is affected in the Drosophilla mutants of raf protoncogene. EMBO J. 1988, 7: 775-781.PubMedPubMedCentral
28.
Lu YP, Lou YR, Xie JG, Peng QY, Liao JYCS, Huang MT, Conney AH: Topical applications of caffeine or (-)-epigallocatechin gallate (EGCG) inhibits carcinogenesis and selectively increase apoptosis in UV B-induced skin tumors in mice. Proc Natl Acad Sci USA. 2002, 99: 12455-12460. 10.1073/pnas.182429899.CrossRefPubMedPubMedCentral
29.
Zhang X, Bommareddy A, Chen W, Hildreth MB, Kaushik R, Zeman D, Khalifa S, Fahmy H, Dwivedi C: Chemopreventive effects of sarcophine-diol on ultraviolet B induced skin tumor development in SKH-1 hairless mice. Marine Drugs. 2009, 7: 153-165. 10.3390/md7020153.CrossRefPubMedPubMedCentral
30.
Zhang X, Bommareddy A, Chen W, Khalifa S, Kaushik RS, Fahmy H, Dwivedi C: Sarcophine -diol, a chemopreventive agent of skin cancer inhibits cell growth and induces apoptosis through extrinsic pathway in human epidermoid carcinoma A431 cells. Translational Oncol. 2009, 2: 21-30.CrossRef
31.
Zhang X, Chen W, Guillermo R, Chandrasekher G, Kaushik RS, Young A, Fahmy H, Dwivedi C: Alpha-santalol, a chemopreventive agent against skin cancer, causes G2/M cell cycle arrest in both p53-mutated human epidermoid carcinoma A431 cells and p53 wild-type human melanoma UACC-62 cells. BMC Res Notes. 2010, 3: 1-15. 10.1186/1756-0500-3-1.CrossRef
32.
Bannon JH, Fichtner I, O'Neill A, Pampillon C, Sweeney NJ, Strohfeldt K, Watson RW, Tacke M, Mc Gee MM: Substituted titanocenes induce caspase-dependent apoptosis in human epidermoid carcinoma cells in vitro and exhibit antitumour activity in vivo. Br J Cancer. 2007, 97: 1234-1241. 10.1038/sj.bjc.6604021.CrossRefPubMedPubMedCentral
33.
Yoshida J, Ishibashi T, Nishio M: Growth-inhibitory Effect of a Streptococcal Antitumor Glycoprotein on Human Epidermoid Carcinoma A431 Cells: Involvement of Dephosphorylation of Epidermal Growth FactorReceptor. Cancer Res. 2001, 61: 6151-6157.PubMed
34.
Masui H, Castro L, Mendelsohn J: Consumption of EGF by A431 Cells: Evidence for Receptor Recycling. J Cell Biol. 1993, 120: 85-93. 10.1083/jcb.120.1.85.CrossRefPubMed
35.
Harper JW, Elledge SJ, Keyomarsi K, Dynlacht B, Tsai LH, Zhang P, Dobrowolski S, Bai C, Connell-Crowley L, Swindell E, Fox MP, Wei N: Inhibition of Cyclin-dependent Kinases by p21. Molecular Biology of the Cell. 1995, 6: 387-400.CrossRefPubMedPubMedCentral
36.
Lee DH, Szczepanski MJ, Lee YJ: Magnolol induces apoptosis via inhibiting the EGFR/PI3K/Akt signaling pathway in human prostate cancer cells. J cell biochem. 2009, 106: 1113-1122. 10.1002/jcb.22098.CrossRefPubMed
37.
Kuo DH, Lai YS, Lo CY, Cheng AC, Wu H, Pan MH: Inhibitory effect of magnolol on TPA-induced skin inflammation and tumor promotion in mice. J Agric Food Chem. 2010, 58: 5777-5783. 10.1021/jf100601r.CrossRefPubMed
38.
Hartwell LH, Kastan M: Cell cycle control and cancer. Science. 1994, 266: 1821-1828. 10.1126/science.7997877.CrossRefPubMed
39.
Li W, Sanki A, Karim RZ, Thompson JF, Soon Lee C, Zhuang L, Mc Carthy SW, Scolyer RA: The role of cell cycle regulatory proteins in the pathogenesis of melanoma. Pathology. 2006, 38: 287-301. 10.1080/00313020600817951.CrossRefPubMed
40.
Sherr CJ, Roberts JM: Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 1995, 9: 1149-1163. 10.1101/gad.9.10.1149.CrossRefPubMed
41.
Chilampalli C, Guillermo R, Kaushik RS, Young A, Chandrasekher G, Fahmy H, Dwivedi C: Honokiol, a chemopreventive agent against skin cancer induces cell cycle arrest and apoptosis in human epidermoid A431 cells. Exp Biol Med. September 9,
42.
Sun SY, Hail NJ, Lotan R: Apoptosis as a novel target for cancer chemoprevention. Natl Cancer Inst. 2004, 96: 662-672. 10.1093/jnci/djh123.CrossRef
43.
Martin SJ, Reutelingsperger C, Mc Gahon AJ, Rader JA, Shie R, LaFace DM, Green DR: Early distribution of plasma membrane phosphatidyl-serine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J Exp med. 1995, 182: 1545-1556. 10.1084/jem.182.5.1545.CrossRefPubMed
44.
Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvesen GS, Dixit VM: Yama/CPP3213, a Mammalian Homolog of CED-3, Is a CrmA-Inhibitable Protease That Cleaves the Death Substrate Poly(ADP-Ribose) Polymerase. Cell. 1995, 81: 801-809. 10.1016/0092-8674(95)90541-3.CrossRefPubMed
45.
Ghobrial IM, Witzig TE, Adjei AA: Targeting Apoptosis Pathways in Cancer Therapy. CA Cancer J Clin. 2005, 55: 178-194. 10.3322/canjclin.55.3.178.CrossRefPubMed
46.
Bowman T, Garcia R, Turkson J, Jove R: STATs in oncogenesis. Oncogene. 2000, 19: 2474-2488. 10.1038/sj.onc.1203527.CrossRefPubMed
47.
Williams JG: STAT signaling in proliferation and development. Curr Opin Genet Dev. 2000, 10: 503-507. 10.1016/S0959-437X(00)00119-2.CrossRefPubMed
48.
Pedranzini L, Leitch A, Bromberg J: Stat3 is required for the development of skin cancer. J Clin Invest. 2004, 114: 720-728.CrossRef
49.
Aaronson DS, Horvath CM: A road map for those who don't know JAK-STAT. Science. 2002, 296: 1653-1655. 10.1126/science.1071545.CrossRefPubMed
50.
Agarwal C, Tyagi A, Kaur M, Agarwal R: Silibinin inhibits constitutive activation of Stat3, and causes caspase activation and apoptotic death of human prostate carcinoma DU145 cells. Carcinogenesis. 2007, 28: 1463-1470. 10.1093/carcin/bgm042.CrossRefPubMed
51.
Hsu YF, Lee TS, Lin SY, Hsu SP, Juan SH, Hsu YH, Zhong WB, Lee WS: Involvement of Ras/Raf-1/ERK actions in the magnolol-induced upregulation of p21 and cell-cycle arrest in colon cancer cells. Mol Carcinog. 2007, 46: 275-283. 10.1002/mc.20274.CrossRefPubMed
52.
Chen LC, Liu YC, Liang YC, Ho YS, Lee WS: Magnolol inhibits human glioblastoma cell proliferation through upregulation of p21/Cip1. J Agric Food Chem. 2009, 57: 7331-7337. 10.1021/jf901477g.CrossRefPubMed
53.
Lee SJ, Cho YH, Park K, Kim EJ, Jung KH, Park SS, Kim WJ, Moon SK: Magnolol elicits activation of the extracellular signal-regulated kinase pathway by inducing p27KIP1-mediated G2/M-phase cell cycle arrest in human urinary bladder cancer 5637 cells. Biochem Pharmacol. 2008, 75: 2289-2230. 10.1016/j.bcp.2008.03.022.CrossRefPubMed
54.
You Q, Li M, Jiao G: Magnolol induces apoptosis via activation of both mitochondrial and death receptor pathways in A375-S2 cells. Arch Pharm Res. 2009, 32: 1789-1794. 10.1007/s12272-009-2218-6.CrossRefPubMed
55.
Tanaka K, Asamitsu KUH, Iddamalgoda A, Ito K, Kojima H, Okamoto T: Protecting skin photoaging by NF-kappaB inhibitor. Curr Drug Metab. 2010, 11: 431-435. 10.2174/138920010791526051.CrossRefPubMed
Metadata
Title
Effects of magnolol on UVB-induced skin cancer development in mice and its possible mechanism of action
Authors
Chandeshwari Chilampalli
Ruth Guillermo
Xiaoying Zhang
Radhey S Kaushik
Alan Young
David Zeman
Michael B Hildreth
Hesham Fahmy
Chandradhar Dwivedi
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-456

Other articles of this Issue 1/2011

BMC Cancer 1/2011 Go to the issue

Research article

MMP28 (epilysin) as a novel promoter of invasion and metastasis in gastric cancer

Research article

Combined mRNA expression levels of members of the urokinase plasminogen activator (uPA) system correlate with disease-associated survival of soft-tissue sarcoma patients

Study protocol

Sequential FDG-PET and induction chemotherapy in locally advanced adenocarcinoma of the Oesophago-gastric junction (AEG): The Heidelberg Imaging program in Cancer of the oesophago-gastric junction during Neoadjuvant treatment: HICON trial

Research article

Phase II study of weekly paclitaxel and capecitabine in patients with metastatic or recurrent esophageal squamous cell carcinoma

Research article

P27Kip1, regulated by glycogen synthase kinase-3β, results in HMBA-induced differentiation of human gastric cancer cells

Research article

Protein and lipid MALDI profiles classify breast cancers according to the intrinsic subtype
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits