Effects of gossypol on O2 consumption and CO2 production in human prostate cancer cells.
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.


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.


CONCLUSIONS
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.
Jiang
Jiahua
J
Laboratory of Reproduction and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus 43210, USA.
Ghosh
Pradip K
PK
Kulp
Samuel K
SK
Sugimoto
Yasuro
Y
Liu
Suling
S
Czekajewski
Jan
J
Chang
Hsiang-Lin
HL
Lin
Young C
YC
D002245:Carbon Dioxide / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006072:Gossypol / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D010100:Oxygen / Q000037:antagonists & inhibitors / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D006131:Growth Inhibitors; D002245:Carbon Dioxide; D013385:Succinate Dehydrogenase; D006072:Gossypol; D010100:Oxygen