The inhibitory effects of gossypol on human prostate cancer cells-PC3 are associated with transforming growth factor beta1 (TGFbeta1) signal transduction pathway.
Jiang J, Sugimoto Y, Liu S, Chang HL, Park KY, Kulp SK, Lin YC.
Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA.
BACKGROUND: Racemic gossypol [(+/-)-GP], a naturally occurring polyphenolic yellow pigment present in cottonseed products, inhibits in vitro proliferation of Dunning prostate cancer cells (MAT-LyLu), human prostate cancer cells derived from a bone marrow metastasis (PC3), MCF-7 and primary cultured human prostate cells. (+/-)-GP also has the ability to inhibit the metastasis of lung and lymph nodes of the androgen-independent rodent prostate cancer cell line, MAT-LyLu, after implantation into Copenhagen rats. MATERIALS AND METHODS: The effects of (+/-)-GP on the proliferation of human prostate cancer PC3 cells were determined by thymidine incorporation assay and doubling-time (DT) determination. The mechanisms of action of (+/-)-GP on the proliferation of PC3 cells were determined by RT-PCR analysis, ELISA assay and Western blot analysis. RESULTS: The results show that (+/-)-GP caused reductions in DNA synthesis and prolonged the DTs in PC3 cells. RT-PCR and ELISA results show that (+/-)-GP elevate the mRNA expression and protein secretion of transforming growth factor beta1 (TGFbeta1) in PC3 cells. Consistent with these findings, (+/-)-GP has been shown to decrease the cyclin D1 mRNA expression and protein expression in PC3 cells. Furthermore, the growth inhibition of PC3 cells by conditioned media collected from the (+/-)-GP-treated-PC3 cells was completely reversed by addition of 25 microg/ml of mouse monoclonal anti-TGFbeta1, -beta2, -beta3 antibody, suggesting the involvement of TGFbeta1 in (+/-)-GP-induced growth inhibition of PC3 cells. CONCLUSION: These results indicate that the inhibitory effects of (+/-)-GP on the proliferation of human prostate cancer PC3 cells are associated with induction of TGFbeta1, which in turn influences the expression of the cell cycle-regulatory protein, cyclin D1, in prostate cancer cells.
PMID: 15015581 [PubMed – indexed for MEDLINE]