Updates on functions of ceramide in chemotherapy-induced cell death and in multidrug resistance

The sphingolipid ceramide, a bioeffector lipid, is known to regulate anti-proliferative responses, such as apoptosis, growth arrest, differentiation and senescence in various human cancer cell lines. Previous studies have demonstrated that many anti-cancer agents cause elevation of endogenous ceramide levels generated via the de novo pathway and/or the hydrolysis of sphingomyelin, accompanied by apoptotic cell death in human cancer cells. It has also been shown that decreased levels of endogenous ceramide by over-expression of glucosylceramide synthase, which clears ceramide levels by incorporating it into glucosylceramide, results in the development of a multidrug resistant phenotype in cancer cells. These studies demonstrate that ceramide plays important roles in the response of cancer cells to chemotherapeutic drugs. The goal of this review is to provide an update on recent studies which shed new light into the roles of ceramide in chemotherapy-induced apoptosis and in multidrug resistance (MDR) in human cancer cells.