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Indole-3-carbinol induces a G1 cell
cycle arrest and inhibits prostate-specific antigen production in human LNCaP
prostate carcinoma cells.
Cancer. 2003 Dec 1;98(11):2511-20.
Zhang J, Hsu B A JC, Kinseth B A MA, Bjeldanes LF, Firestone GL.
Department of Molecular and Cell Biology, University of California at Berkeley,
Berkeley, California 94720-3200, USA.
BACKGROUND: Indole-3-carbinol (I3C), a naturally occurring component of Brassica
vegetables, such as cabbage, broccoli, and Brussels sprouts, is a promising
anticancer agent for certain reproductive tumor cells. The objective of the
current study was to characterize the cell cycle effects of I3C in human
prostate carcinoma cells. METHODS: The incorporation of [(3)H]thymidine and flow
cytometry of propidium iodide-stained nuclei were used to monitor I3C-regulated
changes in prostate carcinoma cell proliferation and cell cycle progression.
Western blotting was used to document expression changes in cell cycle
components and prostate-specific antigen (PSA) levels. The enzymatic activities
of cyclin-dependent kinases (CDK) were tested by in vitro protein kinase assays
using the retinoblastoma protein as a substrate. RESULTS: I3C suppressed the
growth of LNCaP prostate carcinoma cells in a dose-dependent manner by inducing
a G1 block in cell cycle progression. I3C selectively inhibited the expression
of CDK6 protein and transcripts and strongly stimulated the production of the
p16 CDK inhibitor. In vitro protein kinase assays revealed the striking
inhibition by I3C of immunoprecipitated CDK2 enzymatic activity and the
relatively minor down-regulation of CDK4 enzymatic activity. In LNCaP prostate
carcinoma cells, I3C treatment inhibited production of PSA, whereas combinations
of I3C and the androgen antagonist flutamide more effectively inhibited DNA
synthesis and PSA levels compared with either agent alone. CONCLUSIONS: The
results of the current study demonstrated that I3C has a potent
antiproliferative effect in LNCaP and other human prostate carcinoma cells.
These findings implicate this dietary indole as a potential chemotherapeutic
agent for controlling the growth of human prostate carcinoma cells. Copyright
2003 American Cancer Society.
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