Anti-proliferative and proapoptotic effects of (-)-epigallocatechin-3-gallate on human melanoma: Possible implications for the chemoprevention of melanoma

被引:185
|
作者
Nihal, M
Ahmad, N
Mukhtar, H
Wood, GS
机构
[1] Univ Wisconsin, Dept Dermatol, Madison, WI 53706 USA
[2] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA
关键词
green tea; EGCG; melanoma; apoptosis; Bcl-2; family; caspase; cell cycle;
D O I
10.1002/ijc.20785
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Melanoma accounts for only about 4% of all skin cancer cases but most of skin cancer-related deaths. Standard systemic therapies such as interferon (IFN) have not been adequately effective in the management of melanoma. Therefore, novel approaches are needed for prevention and treatment of this disease. Chemoprevention by naturally occurring agents present in food and beverages has shown benefits in certain cancers including nonmelanoma skin cancers. Here, employing 2 human melanoma cell lines (A375 amelanotic malignant melanoma and Hs-294T metastatic melanoma) and normal human epidermal melanocytes (NHEM), we studied the antiproliferative effects of epigallocatechin-3-gallate (EGCG), the major polyphenolic antioxidant present,in green tea. EGCG treatment was found to result in a dose-dependent decrease in the viability and growth of both melanoma cell lines. Interestingly, at similar, EGCG concentrations, the normal melanocytes were not affected. EGCG treatment of the melanoma cell lines resulted in decreased cell proliferation (as assessed by Ki-67 and PCNA protein levels) and induction of apoptosis (as assessed cleavage of PARP, TUNEL assay and JC-1 assay). EGCG also significantly inhibited the colony formation ability of the melanoma cells studied. EGCG treatment of melanoma cells resulted in a downmodulation of anti-apoptotic protein Bcl2, upregulation of proapoptotic Bax and activation of caspases -3, -7 and -9. Furthermore, our data demonstrated that EGCG treatment resulted in a significant, dose-dependent decrease in cyclin D1 and cdk2 protein levels and induction of cyclin kinase inhibitors (ckis) p16(INK4a), p21(WAF1/CIP1) and p27(KIP1). Our data suggest that EGCG causes significant induction of cell cycle arrest and apoptosis of melanoma cells that is mediated via modulations in the cki-cyclin-cdk network and Bcl2 family proteins. Thus, EGCG, alone or in conjunction with current therapies, could be useful for the management of melanoma. (C) 2004 Wiley-Liss, Inc.
引用
收藏
页码:513 / 521
页数:9
相关论文
共 50 条
  • [21] Implications of epigallocatechin-3-gallate in cultured human Sertoli cells glycolytic and oxidative profile
    Dias, Tania R.
    Alves, Marco G.
    Silva, Joaquina
    Barros, Alberto
    Sousa, Mario
    Casal, Susana
    Silva, Branca M.
    Oliveira, Pedro F.
    TOXICOLOGY IN VITRO, 2017, 41 : 214 - 222
  • [22] Mechanisms of polyethylene glycol (PEG) anti-proliferative effects: Implications for colon cancer chemoprevention
    Siddiqui, Shabana
    Koetsier, Jennifer
    Nyhuis, Mary
    Wali, Ramesh
    AMERICAN JOURNAL OF GASTROENTEROLOGY, 2007, 102 : S569 - S569
  • [23] Anti-proliferative and apoptotic effects of HCMV US28 in melanoma cells
    Joshi, Shripad
    Waldhoer, Maria
    Schaider, Helmut
    CANCER RESEARCH, 2009, 69
  • [24] Epigallocatechin-3-gallate exhibits immunomodulatory effects in human primary T cells
    Huang, Shih-Chung
    Kao, Yung-Hsi
    Shih, Shao-Fu
    Tsai, Min-Chien
    Lin, Chin-Sheng
    Chen, Liv Weichien
    Chuang, Yi-Ping
    Tsui, Pi-Fen
    Ho, Ling-Jun
    Lai, Jenn-Haung
    Chen, Sy-Jou
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2021, 550 : 70 - 76
  • [25] SIRT1 is overexpressed in human melanoma cells and its inhibition imparts anti-proliferative effects
    Nihal, M.
    Ndiaye, M.
    Wood, G. S.
    Ahmad, N.
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2011, 131 : S127 - S127
  • [26] Anti-proliferative and pro-apoptotic effects of EGCG and EGCG/IFNa in human melanoma and CTCL lines
    Nihal, M.
    Creswell, C.
    Wood, G. S.
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2007, 127 : S50 - S50
  • [27] Anti-Proliferative and Anti-Migratory Activities of Hispidulin on Human Melanoma A2058 Cells
    Chang, Chi-Jen
    Hung, Yen-Ling
    Chen, Ting-Chen
    Li, Hsin-Ju
    Lo, Yuan-Hsin
    Wu, Nan-Lin
    Chang, Der-Chen
    Hung, Chi-Feng
    BIOMOLECULES, 2021, 11 (07)
  • [28] Epigallocatechin-3-gallate(EGCG) suppresses melanoma cell growth and metastasis by targeting TRAF6 activity
    Zhang, Jianglin
    Lei, Zhou
    Huang, Zunnan
    Zhang, Xu
    Zhou, Youyou
    Luo, Zhongling
    Zeng, Weiqi
    Su, Juan
    Peng, Cong
    Chen, Xiang
    ONCOTARGET, 2016, 7 (48) : 79543 - 79557
  • [29] Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1β secretion
    Ellis, Lixia Z.
    Liu, Weimin
    Luo, Yuchun
    Okamoto, Miyako
    Qu, Dovina
    Dunn, Jeffrey H.
    Fujita, Mayumi
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2011, 414 (03) : 551 - 556
  • [30] Mechanism of sirtuin inhibition mediated anti-proliferative response in human melanoma cells: A proteomics approach
    Singh, C. K.
    George, J.
    Nihal, M.
    Sabat, G.
    Kumar, R.
    Ahmad, N.
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2013, 133 : S240 - S240