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ARS Home » Southeast Area » New Orleans, Louisiana » Southern Regional Research Center » Commodity Utilization Research » Research » Publications at this Location » Publication #194719
Title: EFFECTS OF SERUM ON (-)-GOSSYPOL-SUPPRESSED GROWTH IN HUMAN PROSTATE CANCER CELLS

Author
item HUANG, Y.
item WANG, L.
item CHANG, H.
item YE, W.
item SUGIMOTO, Y.
item Dowd, Michael
item Wan, Peter
item LIN, Y.

Submitted to: Anticancer Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/21/2006
Publication Date: 9/1/2006
Citation: Huang, Y.W., Wang, L.S., Chang, H.L., Ye, W., Sugimoto, Y., Dowd, M.K., Wan, P.J., Lin, Y.C. 2007. Effects of serum on (-)-gossypol-suppressed growth in human prostate cancer cells. Anticancer Research Journal. 26(5A):3613-3620.

Interpretive Summary: Gossypol, a natural compound present in cottonseeds and other parts of the cotton plant, possesses antiproliferative and proapoptotic effects in various cancer cells. Naturally, gossypol is a mixture of right-handed (+) and left-handed (-) optical isomers. The left-handed isomer, (-)-gossypol, is a more potent inhibitor of cancer cell growth. Here, we studied the molecular mechanisms of cell viability inhibition and apoptosis induced by (-)-gossypol in human prostate cancer cells. (-)-Gossypol treatment resulted in growth suppression in both primary cultured human prostate cancer epithelial cells and the prostate cancer cell line, DU-145. Inhibition of cancer cell growth was associated with both down-regulation and up-regulation of some specific molecules and proteins levels. Treatment of cells with 5-10 uM (-)-gossypol significantly enhanced apoptosis measured by DNA fragmentation. Moreover, (-)-gossypol activated caspases-3, -8, and -9 and increased PARP (poly (ADP-ribose) polymerase) cleavage. Furthermore, (-)-gossypol-induced apoptosis might be due to an increase of CAD (caspase-activated deoxyribonuclease) proteins and a decrease of ICAD (inhibitor of CAD) proteins. To further investigate the apoptotic pathways induced by (-)-gossypol, different caspase inhibitors were used to block caspase activities. The data demonstrated that (-)-gossypol resulted in apoptosis via the caspase-dependent pathways. These observations indicate that the apoptotic processes caused by (-)-gossypol in mediated by the regulation of the Bcl-2 and caspase families in human prostate cancer cells. Our data suggest that (-)-gossypol will have chemopreventive benefits in prostate cancer patients as well as in healthy individuals.

Technical Abstract: Gossypol, a natural compound present in cottonseeds, possesses antiproliferative and proapoptotic effects in various cancer cells. The (-)-gossypol enantiomer is a more potent inhibitor of cancer cell growth. Here, we studied the molecular mechanisms of cell viability inhibition and apoptosis induced by (-)-gossypol in human prostate cancer cells. (-)-Gossypol treatment resulted in growth suppression in both primary cultured human prostate cancer epithelial cells and the prostate cancer cell line, DU-145. Inhibition of cancer cell growth was associated with down-regulation of cyclin-D1, Rb, CDK4 and CDK6, and with up-regulation of p21 and TGF-beta1 mRNA and proteins levels, as determined by RT-PCR and Western Blot analyses, respectively. Treatment of cells with 5-10 uM (-)-gossypol significantly enhanced apoptosis measured by DNA fragmentation. We determined that the apoptotic mechanisms might be correlated with down-regulation of Bcl-2 and Bcl-xL and with up-regulation of Bax. Moreover, (-)-gossypol activated caspases-3, -8, and -9 and increased PARP (poly (ADP-ribose) polymerase) cleavage. Furthermore, (-)-gossypol-induced apoptosis might be due to an increase of CAD (caspase-activated deoxyribonuclease) proteins and a decrease of ICAD (inhibitor of CAD) proteins. To further investigate the apoptotic pathways induced by (-)-gossypol, different caspase inhibitors were used to block caspase activities. The data demonstrated that (-)-gossypol resulted in apoptosis via the caspase-dependent pathways. These observations indicate that the apoptotic processes caused by (-)-gossypol in mediated by the regulation of the Bcl-2 and caspase families in human prostate cancer cells. Our data suggest that (-)-gossypol will have chemopreventive benefits in prostate cancer patients as well as in healthy individuals.