Cisplatin Cytotoxicity: DNA and Plasma Membrane Targets

Amelie      Rebillard; Dominique      Lagadic-Gossmann; Marie-Therese      Dimanche-Boitrel

doi:10.2174/092986708786242903

Abstract

Most current anticancer therapies induce tumor cell death through apoptosis where its specific involved pathways are poorly understood. For example, for many DNA-damaging agents, the specific biochemical lesions (DNA adducts) are associated with the induction of apoptosis via the mitochondria death pathway. However, several of these DNA-damaging agents like cisplatin induce apoptosis through plasma membrane disruption, triggering the Fas death receptor pathway. In this review, we focus on the role of early plasma membrane events in cisplatin-induced apoptosis. Special attention is given to changes in plasma membrane fluidity, inhibition of NHE1 exchanger, activation of acid sphingomyelinase and their consequences on the Fas death pathway in response to cisplatin.

Keywords: membrane fluidity, membrane lipid rafts, acid sphingomyelinase, Fas death receptor, Na+/H+ exchanger 1 (NHE1), DNA adducts

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