FTY720, a novel immunosuppressive agent, induces apoptosis in human glioma cells

FTY720, a metabolite from Isaria sinclairii, has been developed to be a potent immunosuppressive drug with induction of apoptosis in T cells and several cell lines, We investigated whether FTY720 induces apoptosis in human glioma cell lines, since they are relatively resistant to multiple apoptotic stimuli, In human glioma cells including T98G, FTY720 induced apoptosis with ED50 between 1 to 10 mug/ml, while etoposide did not induce apoptosis at the same doses. Among the caspase family proteases, mainly caspase-6 was activated during the apoptosis by FTY720 but not etoposide, In addition, FTY720 caused tyrosine dephosphorylation of FAK and did not activate a FAK-P13-kinase survival pathway. This was confirmed also by the observation that orthovanadate prevented FTY720-induced dephosphorylation of FAK and inhibited FTY720-induced cell death, We assumed that FTY720 induced FAK dephosphorylation and cut off the FAK-P13-kinase pathway resulting in the induction of apoptosis via caspase-6 activation in these glioma cells. (C) 2001 Academic Press.