CYTOTOXIC AND APOPTOTIC ACTIVITIES OF MAGAININ II AGAINST HUMAN COLON CANCER CELL LINES

Abstract

Colorectal cancer is the most common form of lower gastrointestinal cancer Conventional chemotherapies are heterogeneous in their mode of action and most of them also act against healthy cells and tissues consequently causing deleterious side effects Antimicrobial peptide AMP magainin II is known to exert broad spectrum anticancer activity that acts preferentially on cancer cells instead of normal cells The present study has explored the effect of magainin in comparison with 5 FU on mutant p53 HT 29 COLO205 COLO 320 DM HCT 15 and wild p53 HCT 116 colon cancer cell lines Our results has shown that magainin is efficacious than 5 FU by exhibiting significant cytotoxicity in wild p 53 colon cancer cell lines than mutant p 53 colon cancer cell lines Magainin acts as potent apoptosis inducer by inhibiting cell growth arresting the cell cycle altering the mitochondrial membrane potential increasing ROS generation reducing telomerase activity and increased release of cytochrome C In addition it has induced p 53 mediated caspase dependent apoptosis by blocking Bcl 2 and activation of B ax expression. In mutant p 53 colon cancer cell lines magainin induced apoptosis via intrinsic mitochondrial pathway whereas in wild p 53 colon cancer cell line apoptosis was induced by magainin through both extrinsic and intrinsic apoptotic pathways as a result of p 53 mediated F as signalling The knowledge of the pathway of magainin induced apoptosis as anti cancer agents could be used to tailor better therapies for colon cancer treatment The in vitro antitumor activity of magainin II in colon cancer is promising but in vivo studies are required to investigate magainin as an efficient agent against colon cancer newline