Mechanism of alpha-lipoic acid-induced apoptosis of lung cancer cells.

Alpha-lipoic acid (LA) shows a protective effect on oxidative stress-induced apoptosis while it induces apoptosis in various cancer cells. Intracellular Ca(2+) plays a central role in triggering apoptotic pathways. In the present study, we aim to investigate whether LA induces apoptosis in lung cancer cells and whether Ca(2+) is involved in LA-induced apoptosis. We found that LA decreased cell viability and increased DNA fragmentation of the cells. LA activated the caspase-independent pathway, determined by upregulation of poly(ADP-ribose) polymerase (PARP) and increased the nuclear level of apoptosis-inducing factor and caspase-dependent apoptotic pathway, determined by increased levels of cytochrome c and PARP-1 cleavage product. LA-induced apoptotic alterations were inhibited in the cells treated with Ca(2+) chelator BAPTA-AM. In conclusion, LA induces apoptosis through caspase-independent and caspase-dependent pathways, which is mediated by intracellular Ca(2+).