Induction of growth inhibition and apoptosis in prostate cancer cells by flavopiridol

Flavopiridol is an inhibitor of several cyclin-dependent kinases, and exhib its potent growth-inhibitory activity against a number of human tumor cell lines both in vitro, and when grown as xenografts in mice. It has shown pro mising antineoplastic activity and is currently undergoing clinical phase I I testing. Prostate cancer (PCa) remains a leading cause of morbidity and m ortality among males in the United States. There are no effective treatment s for hormone and/or radiation refractory PCa, suggesting that novel and ne wer treatment strategy may be useful in the management of PCa. Our previous study showed that flavopiridol induces cell growth inhibition and apoptosi s in breast cancer cells. Here, we investigated whether flavopiridol was ef fective against prostate cancer cells. Flavopiridol was found to inhibit gr owth of PC3 prostate cancer cells. Induction of apoptosis was also observed in PC3 cells treated with flavopiridol, as measured by DNA laddering and P ARP cleavage. We also found a significant down-regulation of Bcl-2 in flavo piridol-treated cells. These findings suggest that down-regulation of Bcl-2 may be one of the molecular mechanisms through which flavopiridol induces apoptosis and inhibits cell growth, suggesting that flavopiridol may be an effective chemotherapeutic agent against prostate cancer.