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Low-dose genistein induces cyclin-dependent kinase inhibitors and G1 cell-cycle arrest in human prostate cancer cells

2000; Wiley; Volume: 29; Issue: 2 Linguagem: Inglês

10.1002/1098-2744(200010)29

1098-2744

Jiancheng Shen, Russell D. Klein, Qingyi Wei, Yongli Guan, John H. Contois, Thomas T. Y. Wang, Shine Chang, Stephen D. Hursting,

Wnt/β-catenin signaling in development and cancer

Molecular CarcinogenesisVolume 29, Issue 2 p. 92-102 Original Article Low-dose genistein induces cyclin-dependent kinase inhibitors and G1 cell-cycle arrest in human prostate cancer cells Jian-Cheng Shen, Jian-Cheng Shen Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorRussell D. Klein, Russell D. Klein Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Science Park–Research Division, Smithville, TexasSearch for more papers by this authorQingyi Wei, Qingyi Wei Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorYongli Guan, Yongli Guan Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorJohn H. Contois, John H. Contois Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorThomas T. Y. Wang, Thomas T. Y. Wang Phytonutrients Laboratory, United States Department of Agriculture, Beltsville, MarylandSearch for more papers by this authorShine Chang, Shine Chang Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorStephen D. Hursting, Corresponding Author Stephen D. Hursting Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Science Park–Research Division, Smithville, TexasOffice of Preventive Oncology, National Cancer Institute, 6130 Executive Boulevard, EPS T-41/MSC 7105, Bethesda, MD 20892.Search for more papers by this author Jian-Cheng Shen, Jian-Cheng Shen Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorRussell D. Klein, Russell D. Klein Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Science Park–Research Division, Smithville, TexasSearch for more papers by this authorQingyi Wei, Qingyi Wei Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorYongli Guan, Yongli Guan Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorJohn H. Contois, John H. Contois Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorThomas T. Y. Wang, Thomas T. Y. Wang Phytonutrients Laboratory, United States Department of Agriculture, Beltsville, MarylandSearch for more papers by this authorShine Chang, Shine Chang Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorStephen D. Hursting, Corresponding Author Stephen D. Hursting Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Science Park–Research Division, Smithville, TexasOffice of Preventive Oncology, National Cancer Institute, 6130 Executive Boulevard, EPS T-41/MSC 7105, Bethesda, MD 20892.Search for more papers by this author First published: 07 November 2000 https://doi.org/10.1002/1098-2744(200010)29:2 3.0.CO;2-QCitations: 92AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract Genistein, a naturally occurring isoflavone found chiefly in soy products, reportedly has antiprostate cancer effects, but the mechanisms underlying these effects are unknown. We studied the antiproliferative and apoptosis-inducing effects of genistein in the androgen-sensitive human prostate cancer cell line LNCaP. Viable cell number was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; cell-cycle progression and apoptosis were evaluated by flow cytometry; apoptosis was also assessed by a histone enzyme-linked immunosorbent assay; and the expression of several cell-cycle– and apoptosis-related genes and their gene products was determined by northern blot analysis, western blot analysis, and/or assays based on polymerase chain reaction. Physiologic concentrations of genistein (≤ 20 μM) decreased LNCaP viable cell number in a dose-dependent manner, induced a G1 cell-cycle block, decreased prostate-specific antigen mRNA expression, and increased p27KIP1 and p21WAF1 (mRNA and protein) but had no effect on apoptosis or the mRNA expression of the apoptosis- and cell-cycle–related markers bcl-2, bax, Rb, and proliferating cell nuclear antigen. Higher concentrations of genistein (> 20 μM) did induce apoptosis. We conclude that genistein (at physiologic concentrations) exerts potent antiproliferative effects on LNCaP cells by inducing a G1 cell-cycle block. The antiproliferative effects of genistein may be mediated by increased levels of p27KIP1 and p21WAF1, which are negative cell-cycle regulators that act as cyclin-dependent kinase inhibitors and that have been recently linked with prostate carcinogenesis. 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