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 cells. A recombinant adenovirus containing pHyde cDNA gene (AdpHyde) was generated to investigate the biological function of pHyde protein. AdpHyde inhibited the growth of human prostate cancer cells. Apoptosis was induced in AdpHyde transduced cells as demonstrated by DAPI (4', 6-diamino-2-phenylindole), TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling) staining, and flow cytometry assays. Apoptosis was also induced in human xenograft prostate cancer tumors growing in nude mice following treatment with AdpHyde. AdpHyde transduction resulted in a dose-dependent stimulation of caspase-3 activity in DU145 cells which was blocked by DEVD (succinyl-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 barely inhibited by pHyde. These results taken together suggest that pHyde inhibits cancer growth by inducing apoptosis through a caspase-3 dependent pathway.
Zhang
X
X
Department of Urology, University of Tennessee Health Science Center, 956 Court Avenue, Memphis, TN 38163, USA.
Steiner
M S
MS
Rinaldy
A
A
Lu
Y
Y
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D053148:Caspase 3; D020169:Caspases / Q000502:physiology*; D018797:Cell Cycle Proteins; D002455:Cell Division; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D010088:Oxidoreductases; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D051381:Rats; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D018797:Cell Cycle Proteins; D015513:Oncogene Proteins; C437943:Steap3 protein, rat; D010088:Oxidoreductases; C486677:STEAP3 protein, human; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases