Effects of (+)-, (-)- and (±)-indenestrols A and B on microtubule distribution and cytotoxicity in Chinese hamster V79 cells

We have reported that (+)-, (-)- and (±)-indenestrols A and B (IA and IB respectively) inhibit the polymerization of microtubule proteins isolated from porcine brain in vitro. In this study, the effects of (+)-, (-)- and (±)-IA and IB on the relative plating efficiency, chromosome number and cellular microtubular architecture of Chinese hamster V79 cells, detected with a fluorescent anti-tubulin antibody, were investigated. The results indicated that the effect of (±)-IA was similar to that of diethylstilbestrol and that of (±)-IB was greater than that of (±)-IA. We also determined the effects of the optically active IA and IB isomers and found that the rank order of cytotoxic activity of the IA and IB series was: (-)-IA>(±)-IA>(+)-IA and (±)-IB≧(-)-IB>(+)-IB. Furthermore, we studied the intracellular disturbance of microtubule formation induced by these compounds and found that (-)-IA had by far the greatest disruptive effect.