Byun Eunyoung, Lim Joo Weon, Kim Jung Mogg, Kim Hyeyoung
Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 120-749, Republic of Korea.
Department of Microbiology, Hanyang University College of Medicine, Seoul 133-791, Republic of Korea.
Mediators Inflamm. 2014;2014:380830. doi: 10.1155/2014/380830. Epub 2014 Aug 19.
Hyperproliferation and oncogene expression are observed in the mucosa of Helicobacter pylori- (H. pylori-) infected patients with gastritis or adenocarcinoma. Expression of oncogenes such as β-catenin and c-myc is related to oxidative stress. α-Lipoic acid (α-LA), a naturally occurring thiol compound, acts as an antioxidant and has an anticancer effect. The aim of this study is to investigate the effect of α-LA on H. pylori-induced hyperproliferation and oncogene expression in gastric epithelial AGS cells by determining cell proliferation (viable cell numbers, thymidine incorporation), levels of reactive oxygen species (ROS), NADPH oxidase activation (enzyme activity, subcellular levels of NADPH oxidase subunits), activation of redox-sensitive transcription factors (NF-κB, AP-1), expression of oncogenes (β-catenin, c-myc), and nuclear localization of β-catenin. Furthermore, we examined whether NADPH oxidase mediates oncogene expression and hyperproliferation in H. pylori-infected AGS cells using treatment of diphenyleneiodonium (DPI), an inhibitor of NADPH oxidase. As a result, α-LA inhibited the activation of NADPH oxidase and, thus, reduced ROS production, resulting in inhibition on activation of NF-κB and AP-1, induction of oncogenes, nuclear translocation of β-catenin, and hyperproliferation in H. pylori-infected AGS cells. DPI inhibited H. pylori-induced activation of NF-κB and AP-1, oncogene expression and hyperproliferation by reducing ROS levels in AGS cells. In conclusion, we propose that inhibiting NADPH oxidase by α-LA could prevent oncogene expression and hyperproliferation occurring in H. pylori-infected gastric epithelial cells.
在感染幽门螺杆菌（H. pylori）的胃炎或腺癌患者的黏膜中观察到细胞过度增殖和癌基因表达。β-连环蛋白和c-myc等癌基因的表达与氧化应激有关。α-硫辛酸（α-LA）是一种天然存在的硫醇化合物，具有抗氧化作用并具有抗癌效果。本研究的目的是通过测定细胞增殖（活细胞数量、胸苷掺入）、活性氧（ROS）水平、NADPH氧化酶激活（酶活性、NADPH氧化酶亚基的亚细胞水平）、氧化还原敏感转录因子（NF-κB、AP-1）的激活、癌基因（β-连环蛋白、c-myc）的表达以及β-连环蛋白的核定位，来研究α-LA对幽门螺杆菌诱导的胃上皮AGS细胞过度增殖和癌基因表达的影响。此外，我们使用NADPH氧化酶抑制剂二苯基碘鎓（DPI）处理，研究NADPH氧化酶是否介导幽门螺杆菌感染的AGS细胞中的癌基因表达和过度增殖。结果，α-LA抑制了NADPH氧化酶的激活，从而减少了ROS的产生，导致幽门螺杆菌感染的AGS细胞中NF-κB和AP-1的激活、癌基因的诱导、β-连环蛋白的核转位以及过度增殖受到抑制。DPI通过降低AGS细胞中的ROS水平，抑制了幽门螺杆菌诱导的NF-κB和AP-1激活、癌基因表达和过度增殖。总之，我们提出α-LA抑制NADPH氧化酶可以预防幽门螺杆菌感染的胃上皮细胞中发生的癌基因表达和过度增殖。
