Redistribution of CD95 into the Lipid Rafts to Treat Cancer Cells?
Bruno Segui and Patrick Legembre
Affiliation: U858 INSERM, BP84225, 31432 Toulouse Cedex 4, France.
Keywords: CD95, apoptosis, ceramide, sphingomyelinase, tumor, chemoresistance, cisplatin, lipid rafts
In a recent patent, Wanebo HJ proposed to increase “apoptosis in a cancer cell comprising contacting the cancer cell with (a) oxaliplatin and (b) C6-ceramide, sequentially or concomitantly”. Cisplatin and derivatives are commonly used in the treatment of solid tumors. Cisplatin induces DNA adducts, which are responsible for the induction of a cellular stress, leading to the elimination of the proliferating cells by apoptosis. Recently, a different mechanism has been reported to explain the tumoricidal action of platinum-based agents. Indeed, cells treated with cisplatin exhibit an increase in plasma membrane fluidity through the activation of acid sphingomyelinase, the subsequent generation of ceramide and the redistribution of the death receptor CD95 into the lipid rafts. This latter event promotes the initiation of the apoptotic signal and the elimination of the malignant cells. In this review, we discuss the potential role played by the death receptor in the potentiation effect of exogenously added ceramide upon the oxaliplatin-mediated cytotoxic effect.
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