Differential effects of (+) and (-) gossypol enantiomers on mitochondrial function and proliferation of cultured TM4 cells.

Abstract

The in vitro effects of (+) and (-)gossypol enantiomers on the mitochondrial functions of mouse transformed Sertoli, TM4 cells were investigated by monitoring mitochondrial rhodamine 123 accumulation. When TM4 cells were cultured in medium without fetal calf serum, 5 micrograms/ml of both enantiomers caused similar declines in mitochondrial rhodamine 123 staining. By contrast, (-)gossypol had a greater adverse action than did (+)gossypol on the mitochondrial of TM4 cells that were cultured in medium supplemented with 2% fetal calf serum. Construction of dose response curves for the effects of the two enantiomers on rhodamine 123 accumulation by TM4 cells after 5 hr of drug treatment gave an EC50 of 7.5 micrograms/ml for the (-)gossypol isomer compared with 18 micrograms/ml for the (+)gossypol isomer. Similarly, TM4 cell proliferation was also more disturbed by (-)gossypol in medium supplemented with other concentrations of fetal calf serum. The results suggest that the lower effect of (+)gossypol on TM4 cells may be attributed to its higher affinity to serum components, which may impede its entrance into TM4 cells.