Volume 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, Texas

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Russell D. Klein

Russell D. Klein

Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Science Park–Research Division, Smithville, Texas

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Qingyi Wei

Qingyi Wei

Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

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Yongli Guan

Yongli Guan

Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

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John H. Contois

John H. Contois

Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

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Thomas T. Y. Wang

Thomas T. Y. Wang

Phytonutrients Laboratory, United States Department of Agriculture, Beltsville, Maryland

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Shine Chang

Shine Chang

Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

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Stephen 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, Texas

Office 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
Citations: 94

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. These findings may provide insights into the mechanisms underlying the apparent antiprostate cancer effects of soy consumption observed in epidemiologic studies. Mol. Carcinog. 29:92–102, 2000. © 2000 Wiley-Liss, Inc.

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