Resumen
FTY720, a sphingosine-1-phosphate (S1P) analog, is a potent immunosuppressant for the treatment of multiple sclerosis. In addition to being an immune modulator, FTY720 also features antitumor activity in several cancer models, but the molecular mechanisms are unclear. Here, we extended our research to analyze the signaling pathways mediating FTY720-induced cell death. FTY720 did not induce apoptotic cell death, autophagy, paraptosis, or necroptosis in glioma cells. Interestingly, FTY720 accumulated in lysosomes, resulting in the induction of lysosomal membrane permeabilization (LMP). Inhibition of LMP by overexpression of HSP70 and cathepsin inhibitors blocked FTY720-induced cell death. These data suggest that FTY720 induces cell death induced by LMP in glioma cells.