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 of these
kinesin Eg5 inhibitors, named K858, exerted important antiproliferative and apoptotic effects on
breast cancer cells. Since
glioblastoma cells usually express high levels of
kinesin Eg5, we tested the effect of K858 on two human
glioblastoma cell lines (U-251 and U-87) and found that K858 inhibited cell growth, induced apoptosis, reversed epithelial-mesenchymal transition and inhibited migration in both cell lines. We also detected that, at the same time, K858 increased the expression of
survivin, an anti-apoptotic molecule, and that the forced down-regulation of
survivin, obtained with the specific inhibitor
YM155, boosted K858-dependent apoptosis. This indicated that the anti-
tumor activity of K858 on
glioblastoma cells is limited by the over-expression of
survivin and that the negative regulation of this
protein sensitizes
tumor cells to K858. These data confirmed that
kinesin Eg5 is an interesting target for new therapeutic approaches for
glioblastoma. We showed that K858, specifically, was a potent inhibitor of replication, an inducer of apoptosis and a negative regulator of the invasive phenotype for
glioblastoma cells.