Phospholipid signals and intestinal carcinogenesis

Abstract

Phospholipids are an important constituent of the cell plasma membrane and are also present in most common dietary products, being particularly abundant in milk, egg, meat and beans. Phospholipids are hydrolysed by different phospholipases to generate multiple breakdown products that affect the fate of the cells. Most phospholipids such as phosphatidylcholine, lysophosphatidylcholine, phosphatidylinositol and platelet activating factor are important for cell survival and thus may promote tumorigenesis and inflammation. Sphingomyelin is unique in the sense that its hydrolysis by sphingomyelinase and ceramidase generates several lipid messengers such as ceramide and sphingosine that inhibit cell proliferation and induce apoptosis. In the intestinal tract there is a specific type of sphingomyelinase called alkaline sphingomyelinase, which can hydrolyse sphingomyelin in both the cell membrane and the diet. The enzyme may play important roles in preventing colon cancer development and inflammation by hydrolysing sphingomyelin to generate anticancer molecules, and by counteracting the cancer-promoting effects of other phospholipids such as lysophosphatidylcholine and platelet activating factor. This mini-review highlights the signal transduction pathways activated by different phospholipids, with special attention being paid to potential implications in the development of colon cancer. Keywords: colon cancer; inflammatory bowel disease; phospholipids; signal transduction pathway; sphingomyelin; sphingomyelinase