Indole-3-carbinol induces a G1 cell cycle arrest and inhibits prostate-specific antigen production in human LNCaP prostate carcinoma cells.
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.
Zhang
Joann
J
Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720-3200, USA.
Hsu B A
Jocelyn C
JC
Kinseth B A
Matthew A
MA
Bjeldanes
Leonard F
LF
Firestone
Gary L
GL
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002277:Carcinoma / Q000473:pathology*; D018844:Cyclin-Dependent Kinases / Q000494:pharmacology; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D017430:Prostate-Specific Antigen / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D007211:Indoles; C016517:indole-3-carbinol; D018844:Cyclin-Dependent Kinases; D017430:Prostate-Specific Antigen