TY - JOUR
T1 - Low-dose genistein induces cyclin-dependent kinase inhibitors and G1 cell-cycle arrest in human prostate cancer cells
AU - Shen, J. C.
AU - Klein, Russell D.
AU - Wei, Qingyi
AU - Guan, Yongli
AU - Contois, John H.
AU - Wang, Thomas T.Y.
AU - Chang, Shine
AU - Hursting, Stephen D.
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2000
Y1 - 2000
N2 - 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 p27(KIP1) and p21(WAF1) (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 p27(KIP1) and p21(WAF1), 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. (C) 2000 Wiley-Liss, Inc.
AB - 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 p27(KIP1) and p21(WAF1) (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 p27(KIP1) and p21(WAF1), 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. (C) 2000 Wiley-Liss, Inc.
KW - Isoflavone
KW - LNCaP
KW - p21(WAF1)
KW - p27(KIP1)
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U2 - 10.1002/1098-2744(200010)29:2<92::AID-MC6>3.0.CO;2-Q
DO - 10.1002/1098-2744(200010)29:2<92::AID-MC6>3.0.CO;2-Q
M3 - Article
C2 - 11074606
AN - SCOPUS:0033763830
SN - 0899-1987
VL - 29
SP - 92
EP - 102
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
IS - 2
ER -