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+).
Choi
Sang Yong
SY
Department of Food and Nutrition, Brain Korea 21 Project, Yonsei University College of Human Ecology, Seoul, Korea.
Yu
Ji Hoon
JH
Kim
Hyeyoung
H
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D008063:Thioctic Acid / Q000494:pharmacology*
D000975:Antioxidants; D051033:Apoptosis Inducing Factor; D002614:Chelating Agents; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D008063:Thioctic Acid; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; D002118:Calcium