Temozolomide induced autophagy stimulates senescence and inhibits apoptosis in glioma cells

Autophagy is a process induced by nutrient limitation and cellular stress, which governs degradation of long-lived proteins and whole organelles, thereby maintaining a balance between synthesis, degradation and recycling of cellular components. Alkylating agents, in particular temozolomide (TMZ), are used as first line chemotherapy of gliomas. TMZ induces several DNA adducts, among which O6-methylguanine (O6MeG) is the most cytotoxic lesion. If not repaired by O6-methylguanine-DNA methyltransferase (MGMT), O6MeG/T mismatch is recognized by the mismatch repair system (MMR) that performs futile repair cycles. Duri…