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Int. J. Mol. Sci. 2014, 15(9), 15754-15765; doi:10.3390/ijms150915754

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

Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
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Received: 14 May 2014 / Revised: 26 August 2014 / Accepted: 3 September 2014 / Published: 5 September 2014
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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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. View Full-Text
Keywords: curcumin; gastric cancer; ROS; ASK1-MKK4-JNK; apoptosis curcumin; gastric cancer; ROS; ASK1-MKK4-JNK; apoptosis
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Liang, T.; Zhang, X.; Xue, W.; Zhao, S.; Zhang, X.; Pei, J. Curcumin Induced Human Gastric Cancer BGC-823 Cells Apoptosis by ROS-Mediated ASK1-MKK4-JNK Stress Signaling Pathway. Int. J. Mol. Sci. 2014, 15, 15754-15765.

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