Ceramide pathway: A novel approach to cancer chemotherapy

Abstract

Apoptosis or programmed cell death applies as a protected way to remove unwanted cells and plays a determinative role in many important biological processes such as normal development and tissue homeostasis in multicellular organisms. The main purpose of studies in this field is to focus on understanding the related regulatory mechanisms and novel approaches to the discovery of anticancer drugs. Among the apoptotic messenger molecules, the key roles of sphingosine and ceramide as the backbone of sphingolipids were considered in many pathways of apoptosis. It has been shown that ceramide plays an important regulatory role in apoptosis and its increased cytoplasmic levels lead to programmed cell death. Ceramide biosynthesis and biodegradation occur via several different enzymes they can be affected by many external factors. Instead, phosphorylated form sphingosine is an important biomarker for cell proliferation and differentiation. Phosphatases, kinases, and proteases are the main operators for ceramide messaging and they can affect different pathways of apoptosis directly or indirectly. Sphingosine is an extracellular ligand for G-protein receptors and an intracellular second messenger to promote cell survival. Many different types of current chemotherapy drugs and some understudy compounds for cancer can at least affect one of the ceramide metabolizing enzymes. Serine palmitoyltransferases, sphingomyelinase, ceramidase, and glucosylceramide synthase are the most important enzymes involved in sphingolipid metabolism have been the discussed in many studies. Consequently, sphingolipids and their related metabolizing enzymes introduced as new pharmacological targets will be helpful in anticancer drug development.