Ceramide as a target of chemotherapy : its role in apoptosis and autophagy

Conventional chemotherapy is the elective and most effective strategy for tumor treatment. Several studies have demonstrated that a mechanism through which most chemotherapeutic agents kill tumor cells is to trigger their death through the generation of ceramide via the activation of enzymes responsible either for its de novo synthesis or for the degradation of sphingomyelin. Ceramide-induced cell death has been widely investigated, with a particular focus on apoptosis. Moreover, recently, the role of ceramide in the induction of autophagy has come to light, opening new questions on how sphingolipid messengers can act in these different but linked pathways. Cellular stress can indeed promote autophagy and apoptosis in multiple ways, including their induction sequentially, simultaneously, or in a mutually exclusive manner. This review presents some of the recent advances regarding the role of ceramide in the induction of apoptosis/autophagy, focusing on its modulation as a strategy for an effective cancer therapy.