Flavopiridol induces cell cycle arrest and apoptosis by interfering with CDK1 signaling pathway and inducing excessive reactive oxygen species in human ovarian granulosa cells

Abstract In recent years, several clinical trials have been conducted to evaluate the use of flavopiridol to treat a variety of cancers, however, it is not clear whether the use of this drug will affect the female reproductive system. Granulosa cells, one of the important cells that constitute the follicle, play a crucial role in determining the reproductive ability of females. In this study, we observed whether different concentrations of flavopiridol have a toxic effect on the growth of immortalized human ovarian granulosa cells. We showed that flavopiridol had an inhibitory effect on cell proliferation at a level of nanomole concentration. Flavopiridol reduced cell proliferation and induced apoptosis by inducing mitochondrial dysfunction and oxidative stress, as well as increasing BAX/BCL2 and pCDK1 levels. These results suggest that reproductive toxicity should be considered when flavopiridol is used to the clinical work.