Lung cancer has been the leading cause of cancer related deaths around the world. The most common type of lung cancer, nearly 85% is Non Small... Show moreLung cancer has been the leading cause of cancer related deaths around the world. The most common type of lung cancer, nearly 85% is Non Small Cell lung Cancer (NSCLC). This study provides an evidence of efficacy of Zapotin (5,6,2',6'-tetramethoxyflavone) against NSCLC cell line. Zapotin was found to be effective against A549 cells that express wild type p53. Since Zapotin increased the protein expression of p53 in A549 cells, its mode of action is expected through p53. Target proteins of p53, which are involved in the cell cycle arrest and apoptosis were found to be up regulated upon treatment of A549 cells with Zapotin. Effects of Zapotin were tested on the proteins involved in induction and stabilization of p53 viz. ATM, p300, Mdm2, Mdm4 and Snai1. A549 cells possess oncogeneic K-ras, which suppresses the p53 activity through a Snai1 mediated pathway of p53 degradation. Further translational inhibition studies provided an evidence of p53 stabilization rather than induction of p53 by Zapotin. Our results here indicate restoration of p53 function in NSCLC cells treated with Zapotin through the inactivation of Snai1 in K-Ras mutated cells with wild type p53. M.S. in Biology, May 2011 Show less
