Characterization of apoptosis induced by marine naturalproducts in non small cell lung cancer A549 cells

Abstract. The effects of different marine derived agents were studied in A549 cell growth. These drugs induced cell cycle arrest at the G2-M phase associated with the up-regulation of GADD45α−γ and down-regulation of c-Myc. In treated cells, GADD45α−γ and c-Myc were up- and down-regulated, respectively. A cascade of events leading to apoptotic mitochondrial ‘intrinsic’ pathway was observed in treated cells: (1) dephosphorylation of BAD serine136; (2) BAD dissociation from 14-3-3 followed by its association with BCL-XL; (3) cytochrome c release; (4) caspase-3 activation, and (5) cleavage of vimentin. Caspase(s) inhibitor prevented the formation of cleavage products and, in turn, apoptosis was inhibited through a p53-independent mechanism. Moreover, these compounds did not activate NF-κ B. Our findings may offer new insights into the mechanisms of action of these agents in A549 cells. The better understanding of their effects might be important to fully exploit the potential of these new drugs.