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Cisplatin,a DNA crosslinking agent,is widely used for the treatment of a variety of solid tumors.Numerous studies have demonstrated that sphingolipid metabolism,which acts as a target for cisplatin treatment,is a highly complex network that consists of sphingolipid signaling molecules and related catalytic enzymes.Ceramide(Cer),which is the central molecule of this network,has been established to induce apoptosis.However,another molecule,sphingosine-1-phosphate(S1P),exerts the opposite function,i.e.,serves as a regulator of pro-survival.Other sphingolipid molecules,including dihydroceramide,ceramide-1-phosphate,glucosylceramide(Glu Cer),and sphingosine(Sph),or sphingolipid catalytic enzymes such as Sph kinase(Sph K),Cer synthase(Cer S),and S1 P lyase,have also attracted considerable attention,particularly Cer,Glu Cer,Sph K,Cer S,and S1 P lyase,which have been implicated in cisplatin resistance.This review summarizes specific molecules involved in sphingolipid metabolism and related catalytic enzymes affecting the anticancer effect of cisplatin,particularly in relation to induction of apoptosis and drug resistance.
Cisplatin, a DNA crosslinking agent, is widely used for the treatment of a variety of solid tumors. Numerous studies have demonstrated that sphingolipid metabolism, which acts as a target for cisplatin treatment, is a highly complex network that consists of sphingolipid signaling molecules and related catalytic enzymes. Ceramide (Cer), which is the central molecule of this network, has been established to induce apoptosis. Yet another molecule, sphingosine-1-phosphate (S1P), exerts the opposite function, ie, serves as a regulator of pro-survival. Other sphingolipid molecules, including dihydroceramide, ceramide-1-phosphate, glucosylceramide (Glu Cer), and sphingosine (Sph), or sphingolipid catalytic enzymes such as Sph kinase (Sph K), Cer synthase S1 P lyase, have also attracted attracted attention, particularly Cer, Glu Cer, Sph K, Cer S, and S1 P lyase, which have been implicated in cisplatin resistance. This review summarizes specific molecules involved in sphingolipid metabolism and related cats alytic enzymes affecting the anticancer effect of cisplatin, particularly in relation to induction of apoptosis and drug resistance.