(-)-gossypol-enriched cottonseed oil induces apoptosis in multi-drug resistant human breast cancer cells.

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Chemotherapy remains an important option in breast cancer treatment. However, emergence of resistance to chemotherapeutic agents is a concern for breast cancer therapy. Increasing evidence indicates that resistance may be associated with defects, or dysregulation of, different steps of the apoptotic pathway. Recently research showed that gossypol (GP) possesses anti-neoplastic activity against a variety of malignant cell types in vitro and in vivo. We investigate the effect of (-)-gossypol-enriched cottonseed oil [(-)-GPCSO], which contains 65% of (-)-GP and 35% of (+)-GP on induction of apoptosis in a multi-drug resistant human breast cancer cell line, MCF-7 Adr and primary cultured human breast cancer epithelial cells (PCHBCECs) using non-radioactive cell proliferation assay, quick apoptotic DNA ladder detection, RT-PCR and Western Blotting analysis after two types of cells were treated with 0.025, 0.05 and 0.1% of (-)-GPCSO for 24 hours. Our results demonstrated that (-)-GPCSO inhibited proliferation and induced DNA fragmentation in a dose-dependent manner in both cell types. 0.05 and 0.1% of (-)-GPCSO significantly decreased Bcl-2 mRNA and protein expression in MCF-7 Adr cells to 14 and 32%, and 65 and 82% respectively. In PCHBCECs, the same concentrations of (-)-GPCSO treatment significantly reduced Bcl-2 mRNA and protein expression to 60 and 93% and 71 and 76%, respectively. Evaluation of the effect of (-)-GPCSO on Bax mRNA and protein expression was also performed. Compared to controls, treatment of 0.025, 0.05 and 0.1% of (-)-GPCSO significantly increased Bax mRNA expression to 40, 47, 116% in MCF-7 Adr cells, and 100, 123, 423% in PCHBCECs. The same concentrations of (-)-GPCSO significantly up-regulated Bax protein expression to 27, 50 and 62% in MCF-7 Adr cells. Our results demonstrated that (-)-GPCSO possesses potent anti-mitogenic effects on human breast cancer cells, its ability in suppressing breast cancer cell proliferation may be mediated through down-regulation of Bcl-2 and up-regulation of Bax expression in both mRNA and protein levels. Our experimental data suggest that natural food components, (-)-GPCSO might serve as low costs and effective chemopreventive ingredients for healthy consumers and anti-multidrug resistance food components for breast cancer patients (Supported by NIH Grants CA94718 & CA95915, and Cotton Incorporated Project 06-864).