Flavopiridol`s antiproliferative effects in glioblastoma cell lines

Flavopiridol?s Antiproliferative Effects in Glioblastoma Cell LinesGlioblastoma multiforme is largely refractory to operation, radiation and chemotherapy therapies in use today, in part, accounting for the survivals of affected patients between 12 to 16 mounths generally . GBM associated mostly with deregulation of the three major cell cycle pathways: P16INK4A-SiklinD1-CDK4-pRb ve p14ARF-MDM2?p53 tumor suppressor pathways and EGFR-Akt-PI3K proliferation pathway. The most frequently altered genes in GBM are p53, EGFR, PTEN and CDKN2A.Our aim is to investigate of the effect of Flavopiridol, a CDK and spesific phosphokinase inhibitor, on glioblastoma cell lines having different genetic profiles: U87MG, U118MG and T98G. According to our findings, via Rb and p53 tumor suppressor pathways, Flavopiridol induced apoptosis in all cell lines through but a caspase-3/7 independent mechanism. Flavopiridol treatment did not induce expression of Bax and Bim pro-apoptotic proteins that are members of Bcl-2 family in glioblastoma cells. Down-regulation of the cyclin D1, c-myc, p53 proteins activities, up-regulation of the protein p27Kip1 activity and G1/S cell cycle arrest were seen respectively after Flavopiridol treatment. Additionally, Flavopiridol diminished p-Akt protein levels generally that induce inhibition of proliferation.The present study demonstrated that Flavopiridol, induces apoptosis independent of caspase-3/7 activation, Bim and Bax pro-apoptotic proteins. Additionally, it leads to the expression changes of various proteins that inhibits proliferation and eternity in glioblastoma cell lines which have different genetic alteretions.Key words: U118MG, U87MG, T98G, Glioblastoma multiforme, Flavopiridol