BACKGROUND: Gossypol (GP) is a potent antifertility agent contained in cottonseed and other parts of cotton plants. We have shown that GP inhibits in vitro growth of Dunning rodent prostate cancer cells (MAT-LyLu), PC3, MCF-7 and primary cultured human prostate cells, as well as the in vivo tumor growth of the MAT-LyLu cell line after implantation into Copenhagen rats. MATERIALS AND METHODS: GP's effects on O2 consumption/CO2 production of PC3 cells were studied using the Micro-Oxymax respirometer. The effects of GP on oxidative phosphorylation in PC3 cells were determined by the succinic dehydrogenase assay. RESULTS: GP at the concentration of 1.0 microM reduced DNA synthesis by 25.6%, 54.6% and 81.25% after treatment times of 24, 28, and 32 hours, respectively, while GP at 2 microM reduced DNA synthesis by 78.57%, 81.44% and 83.72% after treatment durations of 24, 28 and 32 hours, respectively. GP at the concentration of 2.0 microM decreased significantly CO2 production by 37.5%, 42.4% and 44.7% and O2 consumption by 6.4%, 6.9% and 7.9% in PC3 cells after the different periods of treatment (24, 28 and 32 hours, respectively). GP at the concentration of 1.0 microM did not significantly inhibit O2 consumption/CO2 production of PC3 cells. GP also reduced the activity of mitochondrial succinic dehydrogenase in PC3 cells to 31% of control at the concentration of 1.0 microM and 15% of control at the concentration of 2.0 microM. CONCLUSION: The inhibitory action of GP on O2 consumption/CO2 production of PC3 cells may be due to disruption of oxidative phosphorylation by inhibition of mitochondrial succinic dehydrogenase.
BACKGROUND:Gossypol (GP) is a potent antifertility agent contained in cottonseed and other parts of cotton plants. We have shown that GP inhibits in vitro growth of Dunning rodent prostate cancer cells (MAT-LyLu), PC3, MCF-7 and primary cultured human prostate cells, as well as the in vivo tumor growth of the MAT-LyLu cell line after implantation into Copenhagen rats. MATERIALS AND METHODS:GP's effects on O2 consumption/CO2 production of PC3 cells were studied using the Micro-Oxymax respirometer. The effects of GP on oxidative phosphorylation in PC3 cells were determined by the succinic dehydrogenase assay. RESULTS:GP at the concentration of 1.0 microM reduced DNA synthesis by 25.6%, 54.6% and 81.25% after treatment times of 24, 28, and 32 hours, respectively, while GP at 2 microM reduced DNA synthesis by 78.57%, 81.44% and 83.72% after treatment durations of 24, 28 and 32 hours, respectively. GP at the concentration of 2.0 microM decreased significantly CO2 production by 37.5%, 42.4% and 44.7% and O2 consumption by 6.4%, 6.9% and 7.9% in PC3 cells after the different periods of treatment (24, 28 and 32 hours, respectively). GP at the concentration of 1.0 microM did not significantly inhibit O2 consumption/CO2 production of PC3 cells. GP also reduced the activity of mitochondrial succinic dehydrogenase in PC3 cells to 31% of control at the concentration of 1.0 microM and 15% of control at the concentration of 2.0 microM. CONCLUSION: The inhibitory action of GP on O2 consumption/CO2 production of PC3 cells may be due to disruption of oxidative phosphorylation by inhibition of mitochondrial succinic dehydrogenase.