The inhibitory action of taxol on granulosa cell steroidogenesis is reversible

Abstract

Taxol is a novel anticancer agent extracted from the bark of Pacific yew trees. The drug has been approved by the FDA for the treatment of advanced ovarian cancer and is in clinical trials for other malignancies, including breast cancer. The goals of this study were to determine whether taxol adversely and irreversibly affects ovarian granulosa cell steroidogenesis. Cultured porcine granulosa cells were treated with taxol (0.12-12 microM) or vehicle (0.01-1% ethanol) in the absence or presence of 10(-9) M hCG in a time- and dose-response study. Morphological changes were recorded every 2 h, and media were collected for the measurement of progesterone (P4) and 17 beta-estradiol. Taxol suppressed both basal P4 and 17 beta-estradiol production and hCG-stimulated P4 production in a time- and dose-dependent manner and drastically changed cell shape by causing disorganization of microtubule bundles and other subcellular organelles. hCG partially reversed the steroid inhibition induced by taxol. These changes are not attributed to ethanol used as the vehicle, because ethanol at higher concentrations than that present in taxol did not suppress P4 production. When taxol was removed from the culture, P4 production returned to control levels. The results of this study show that taxol causes a significant, but reversible, inhibition of granulosa cell steroidogenesis. This inhibitory effect can be partially overcome by co-treatment with hCG.