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Title: LOW DOSE GENISTEIN INDUCES CYCLIN-DEPENDENT KINASE INHIBITORS AND G1 CELL CYCLE ARREST IN HUMAN PROSTATE CANCER CELLS

Author
item SHEN, JIAN-CHENG - MD ANDERSON
item KLEIN, RUSSEL - MD ANDERSON
item WEI, QINGYI - MD ANDERSON
item GUAN, YONGLI - MD ANDERSON
item CONTOIS, JOHN - MD ANDERSON
item Wang, Thomas - Tom
item CHANG, SHINE - MD ANDERSON
item HURSTING, STEPHEN - MD ANDERSON

Submitted to: Carcinogenesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/1/2001
Publication Date: N/A
Citation: N/A

Interpretive Summary: Genistein, a naturally occurring isoflavone found chiefly in soy products, reportedly has anti-prostate cancer effects but the mechanisms underlying these effects are unknown. We studied the proliferation inhibitory and apoptosis (cell death) inducing effects of genistein in the androgen (male sex hormone)-sensitive human prostate cancer cell line LNCaP. We found that at physiological concentrations genistein prevented cell cycle progression resulting in inhibition of cell proliferation. At pharmacological concentrations gensitein inhibited cell cycle and induced apoptosis of LNCap cells. We conclude that genistein, at physiologic concentrations, exerts potent proliferation inhibitory effects on LNCaP cells by inducing a block in cell cycle. These findings provide insights into the mechanisms underlying the apparent anti-prostate cancer effects of soy consumption observed in epidemiologic studies. This information will be useful to scientists in the field of nutrition and cancer prevention studies.

Technical Abstract: Genistein, a naturally occurring isoflavone found chiefly in soy products, reportedly has anti-prostate cancer effects but the mechanisms underlying these effects are unknown. We studied the anti-proliferative and apoptosis-inducing effects of genistein in the androgen-sensitive human prostate cancer cell line LNCaP. Viable cell number was assessed by the MTT assay; cell cycle progression and apoptosis were evaluated by flow cytometry; apoptosis was also assessed by histone enzyme-Iinked immunosorbent assay; and the expression of prostate specific antigen (PSA) and several cell-cylce and apoptotic-related genes and their gene products was determined by northern blot analysis, Western blot analysis, and/or polymerase chain reaction (PCA)-based assays Physiologic concentrations of genistein (5 20 uM)decreased LNCap viable cell number in a dose-dependent manner, induced a G1 cell cycle block, decreased PSA mANA expression, increased p27KIP1 and p21 WAF1 (mANA and protein) but had no effect on apoptosis or the mANA expression of the apoptosis-and cell-cycle-related markers Scl-2, Sax, Ab, or proliferating cell nuclear antigen (PCNA). Higher concentrations of gensitein (>20 uM) did induce apoptosis. We conclude that genistein (at physiologic concentrations) exerts potent anti-proliferative 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 anti-prostate cancer effects of soy consumption observed in epidemiologic studies.