A Review of the Role of Sphingolipids in Apoptosis Phenomenon

Cancer is one of the major health problems in the world and chemotherapy is still the most common solution for its treatment. A great deal of studies in this area have been devoted to evaluating the occurrence of apoptosis as a key factor in preventing cell's escape from cell cycle regulation mechanisms. The aim of this study is to summarize the studies on metabolism, messenger pathways and effective pharmaceutical factors on sphingolipids involved in apoptosis. In this review article, the national and international databases of PubMed, Scopus, Google Scholar, Web of Science, ISC and Magiran were searched for the keywords “apoptosis”, “sphingolipids”, “ceramide”, “sphingosine” and “cancer” without time limit and the related material was collected. Among the apoptotic messenger molecules, the key role of the sphingosine and ceramide has been considered as the cornerstone of sphingolipids in many of its controlling processes. It has been shown that ceramide is a key regulator in apoptosis, and increase in its cytoplasmic levels increase the proliferation of cascades resulting in programmed cell death. The bio-production and bio-destruction of ceramide is accomplished by the activity of several enzymes, and much evidence suggests the effect of external factors on enzyme systems. In contrast, the phosphorylated form of sphingosine is an important index for guiding cells toward proliferation and differentiation. It has been found that several commonly used chemotherapy drugs and compounds that are being studied in the treatment of cancer affect at least one of the enzymes of sphingolipids metabolism. Sphingolipids and the enzymes involved in their metabolism are introduced as new pharmacological targets for the induction of apoptosis, and it is obvious that analyzing the effective therapeutic factors and the ways of controlling them would be helpful in finding anticancer drugs.