Apoptosis induction in prostate cancer cells by a novel gene product, pHyde, involves caspase-3

A novel gene, pHyde, was recently cloned from Dunning rat prostate cancer c ells. A recombinant adenovirus containing pHyde cDNA gene (AdpHyde) was gen erated to investigate the biological function of pHyde protein. AdpHyde inh ibited the growth of human prostate cancer cells. Apoptosis was induced in AdpHyde transduced cells as demonstrated by DAPI (4', 6-diamino-2-phenylind ole), TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick and l abeling) staining, and flow cytometry assays. Apoptosis was also induced in human xenograft prostate cancer tumors growing in nude mice following trea tment with AdpHyde. AdpHyde transduction resulted in a dose-dependent stimu lation of caspase-3 activity in DU145 cells which was blocked by DEVD (succ inyl-Asp-Glu-Val-Asp-aldehyde) and VAD (benzyloxycarbonyl - Val - Ala - Asp -fluoromethylketone), inhibitors specifically against caspase-3. Moreover, cancer cells that lacked expression of endogenous caspase-3 were not or ba rely inhibited by pHyde. These results taken together suggest that pHyde in hibits cancer growth by inducing apoptosis through a caspase-3 dependent pa thway.