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However, the anti\u2010cancer effect of JS\u2010K in gastric cancer has not been reported. In this study, we found that JS\u2010K inhibited the proliferation of gastric cancer cells in vitro and in vivo and triggered mitochondrial apoptosis. Moreover, JS\u2010K induced a significant accumulation of reactive oxygen species (ROS), and the clearance of ROS by antioxidant reagents reversed JS\u2010K\u2010induced toxicity in gastric cancer cells and subcutaneous xenografts. Although JS\u2010K triggered significant NO release, NO scavenging had no effect on JS\u2010K\u2010induced toxicity in vivo and in vitro. Therefore, ROS, but not NO, mediated the anti\u2010cancer effects of JS\u2010K in gastric cancer. We also explored the potential mechanism of JS\u2010K\u2010induced ROS accumulation and found that JS\u2010K significantly down\u2010regulated the core proteins of mitochondria respiratory chain (MRC) complex I and IV, resulting in the reduction of MRC complex I and IV activity and the subsequent ROS production. Moreover, JS\u2010K inhibited the expression of antioxidant enzymes, including copper\u2010zinc\u2010containing superoxide dismutase (SOD1) and catalase, which contributed to the decrease of antioxidant enzymes activity and the subsequent inhibition of ROS clearance. Therefore, JS\u2010K may target MRC complex I and IV and antioxidant enzymes to exert ROS\u2010dependent anti\u2010cancer function, leading to the potential usage of JS\u2010K in the prevention and treatment of gastric cancer.<\/jats:p>","DOI":"10.1111\/jcmm.14122","type":"journal-article","created":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T10:06:41Z","timestamp":1548324401000},"page":"2489-2504","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["JS\u2010K induces reactive oxygen species\u2010dependent anti\u2010cancer effects by targeting mitochondria respiratory chain complexes in gastric cancer"],"prefix":"10.1111","volume":"23","author":[{"given":"Xudong","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of General Surgery Chinese People's Liberation Army General Hospital Beijing 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