Choi Sang Yong, Yu Ji Hoon, Kim Hyeyoung
Department of Food and Nutrition, Brain Korea 21 Project, Yonsei University College of Human Ecology, Seoul, Korea.
Ann N Y Acad Sci. 2009 Aug;1171:149-55. doi: 10.1111/j.1749-6632.2009.04708.x.
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+).
α-硫辛酸（LA）对氧化应激诱导的细胞凋亡具有保护作用，而它在多种癌细胞中可诱导细胞凋亡。细胞内钙离子（Ca(2+)）在触发凋亡途径中起核心作用。在本研究中，我们旨在探究LA是否在肺癌细胞中诱导细胞凋亡以及Ca(2+)是否参与LA诱导的细胞凋亡。我们发现LA降低了细胞活力并增加了细胞的DNA片段化。LA激活了半胱天冬酶非依赖性途径，这通过聚（ADP-核糖）聚合酶（PARP）的上调来确定，并且增加了凋亡诱导因子的核水平以及半胱天冬酶依赖性凋亡途径，这通过细胞色素c和PARP-1裂解产物水平的增加来确定。在用Ca(2+)螯合剂BAPTA-AM处理的细胞中，LA诱导的凋亡改变受到抑制。总之，LA通过半胱天冬酶非依赖性和半胱天冬酶依赖性途径诱导细胞凋亡，这由细胞内Ca(2+)介导。
