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Title: Induction of apoptosis by (-)-gossypol-enriched cottonseed oil in human breast cancer cells

Author
item YE, WEIPING - The Ohio State University
item CHANG, HSIANG-LIN - The Ohio State University
item WANG, LI-SHU - The Ohio State University
item HUANG, YI-WEN - The Ohio State University
item SHU, SHERRY - The Ohio State University
item SUGIMOTO, YASURO - The Ohio State University
item Dowd, Michael
item Wan, Peter
item LIN, YOUNG - The Ohio State University

Submitted to: International Journal of Molecular Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/10/2009
Publication Date: 7/1/2010
Citation: Ye, W., Chang, H.-L., Wang, L.-S., Huang, Y.-W., Shu, S., Sugimoto, Y., Dowd, M.K., Wan, P.J., Lin, Y.C. 2010. Induction of apoptosis by (-)-gossypol-enriched cottonseed oil in human breast cancer cells. International Journal of Molecular Medicine. 26(1):113-119.

Interpretive Summary: Experiments were conducted with (-)-gossypol enriched cottonseed oil to demonstrate that the compound inhibits the progression of some cancer cell lines. The effect was found to occur in a dose-dependent manner. The results appeared to correlate with a reduction of in Bcl-2 proteins and DNA fragmentation suggesting that the gossypol was allowing normal cell apoptosis to occur in these cancer cells. The results will be of interest to researchers developing cancer therapies.

Technical Abstract: Induction of apoptosis is one of the mechanisms of chemotherapeutic agents against breast cancer. In addition, recent studies have shown that diets containing polyphenolic components possess anticancer activities either in vitro or in vivo by inhibiting cell proliferation and inducing apoptosis. The aim of our study was to explore the effects of (-)-gossypol-enriched cottonseed oil [(-)-GPCSO], a polyphenolic compound, on the proliferation of the breast cancer cell line MCF-7 as well as primary cultured human breast cancer epithelial cells (PCHBCEC). We investigated whether the mechanism of the effects of (-)-GPCSO was mediated via the induction of cell apoptosis and the regulation of Cvl-2 gene expression at both the mRNA and protein levels. Our results showed that (-)-GPCSO inhibited the proliferation of MCF-7 and PCHBCEC in a dose-dependent manner. (-)-GPCSO (0.1 and 0.2%) induced DNA fragmentation n both MCF-7 cells and PCHBCEC. (-)-GPCOS suppressed the expression of Bcl-2 at both the mRNA and protein levels in MCF-7 and PCHBCEC in a dose-dependent fashion. Our results suggest that the growth inhibitory effect of (-)-GPCSO on MCF-7 and PCHBCEC is due, at least partially, to the induction of cell apoptosis, which is mediated by down-regulation of Bcl-2 expression at both the mRNA and protein levels. It might be possible for (-)-GPCSO to be developed as a novel chemotherapeutic agent for breast cancer patients.