The kinesin Eg5 inhibitor K858 induces apoptosis and reverses the malignant invasive phenotype in human glioblastoma cells

摘要: Glioblastoma multiforme is the most common primary malignant brain tumor and its current chemotherapeutic options are limited to temozolomide. Recently, some synthetic compounds acting as inhibitors of kinesin spindle protein Eg5 have shown pronounced antitumor activity. Our group has recently demonstrated that one these inhibitors, named K858, exerted important antiproliferative apoptotic effects on breast cancer cells. Since glioblastoma cells usually express high levels Eg5, we tested effect K858 two human cell lines (U-251 U-87) found inhibited growth, induced apoptosis, reversed epithelial-mesenchymal transition migration in both lines. We also detected that, at same time, increased expression survivin, an anti-apoptotic molecule, forced down-regulation obtained with specific inhibitor YM155, boosted K858-dependent apoptosis. This indicated anti-tumor activity by over-expression survivin negative regulation this sensitizes K858. These data confirmed interesting target for new therapeutic approaches glioblastoma. showed specifically, was a potent replication, inducer apoptosis regulator invasive phenotype