Indole3-carbinol (I3C) induced cell growth inhibition, G1 cell cycle arrest and apoptosis in prostate cancer cells

Prostate cancer is one of the most common cancers in men and it is the seco nd leading cause of cancer related death in men in the United States. Recen t dietary and epidemiological studies have suggested the benefit of dietary intake of fruits and vegetables in lowering the incidence of prostate canc er. A diet rich in fruits and vegetables provides phytochemicals, particula rly indole-3-carbinol (I3C), which may be responsible for the prevention of many types of cancer, including hormone-related cancers such as prostate. Studies to elucidate the role and the molecular mechanism(s) of action of I 3C in prostate cancer, however, have not been conducted. In the current stu dy, we investigated whether I3C had any effect against prostate cancer cell s and, if so, attempts were made to identify the potential molecular mechan ism(s) by which I3C elicits its biological effects on prostate cancer cells . Here we report for the first time that I3C inhibits the growth of PC-3 pr ostate cancer cells. Induction of G1 cell cycle arrest was also observed in PC-3 cells treated with I3C, which may be due to the observed effects of I 3C in the up-regulation of p21(WAF1) and p27(Klp1) CDK inhibitors, followed by their association with cyclin D1 and E and down-regulation of CDK6 prot ein kinase levels and activity. The induction of p21(WAF1) appears to be tr anscriptionally upregulated and independent of the p53 responsive element. In addition, I3C inhibited the hyperpohosphorylation of the Retinoblastoma (Rb) protein in PC-3 cells. Induction of apoptosis was also observed in thi s cell line when treated with I3C, as measured by DNA laddering and poly (A DP-ribose) polymersae (PARP) cleavage. We also found an up-regulation of Ba x, and down-regulation of Bcl-2 in I3C-treated cells. These effects may als o be mediated by the down-regulation of NF-kappaB observed in I3C treated P C-3 cells. From these results, we conclude that I3C inhibits the growth of PC-3 prostate cancer cells by inducing G1 cell cycle arrest leading to apop tosis, and regulates the expression of apoptosis-related genes. These findi ngs suggest that I3C may be an effective chemopreventive or therapeutic age nt against prostate! cancer. Oncogene (2001) 20, 2927-2936.