Curcumin Induced Human Gastric Cancer BGC-823 Cells Apoptosis by ROS-Mediated ASK1-MKK4-JNK Stress Signaling Pathway

International Journal of Molecular Sciences

Tao Liang²  Xiaojian Zhang¹  Wenhua Xue²  Songfeng Zhao²  Xiang Zhang² 

[1] Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China;

关键词: curcumin;    gastric cancer;    ROS;    ASK1-MKK4-JNK;    apoptosis;   

DOI  :  10.3390/ijms150915754

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.