title: Curcumin induced human gastric cancer BGC-823 cells apoptosis by ROS-mediated ASK1-MKK4-JNK stress signaling pathway.
abstract: The signaling mediated by stress-activated MAP kinases (MAPK), c-Jun N-terminal kinase (JNK) has well-established importance in cancer. In the present report, we investigated the effects of curcumin on the signaling pathway in human gastric cancer BGC-823 cells. Curcumin induced reactive oxygen species (ROS) production and BGC-823 cells apoptosis. Inhibition of ROS generation by antioxidant (NAC or Trion) significantly prevented curcumin-mediated apoptosis. Notably, we observed that curcumin activated ASK1, a MAPKKK that is oxidative stress sensitive and responsible to phosphorylation of JNK via triggering cascades, up-regulated an upstream effector of the JNK, MKK4, and phosphorylated JNK protein expression in BGC-823 cells. However, curcumin induced ASK1-MKK4-JNK signaling was attenuated by NAC. All the findings confirm the possibility that oxidative stress-activated ASK1-MKK4-JNK signaling cascade promotes the apoptotic response in curcumin-treated BGC-823 cells.
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. liangtaozhz@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Liang
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. zhxj0524@sina.com.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. xuewenhua77@163.com.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Xue
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. zhaosf450@126.com.
authors.forename: Songfeng
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. zhangxiang028@126.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. jianyingpei@126.com.
authors.forename: Jianying
authors.initials: J
authors.lastname: Pei
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human; D048670:MAP Kinase Kinase 4; C482559:MAP2K4 protein, human; D003474:Curcumin