Comparative Study on Induction of Apoptosis in A549 Human Lung Adenocarcinoma Cells by C2 Ceramide or Ceranib-2

Abstract

Investigation of ceramide and ceramidases on cancer therapy had become popular in recent years. Ceramide is a metabolite in sphingolipid pathway of the cells that has an ability to promote cell death in tumor cells when produced endogenously in the cells or applied exogenously. Ceramidases, which are main component of ceramide pathway catalyze metabolism of proapoptotic ceramide to anti-apoptotic sphingosine and other fatty acids. In this study we have evaluated the pro-apoptotic effect of ceranib-2, a human ceramidase inhibitor and of a short-chain C2 ceramide on human lung adenocarcinoma cells, A549 by determining cytotoxicity of these agents by trypan blue assay, apoptosis inducing ability by annexin V and JC-l staining and ultrastructural alterations by transmission electron microscopy. Our data clearly shows that ceranib-2 is more effective than C2 ceramide in promoting apoptosis. The cytotoxic effects of these components cause ultrastructural changes in A549 cells.