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

被引：81

作者：

Liang, Tao ^{[1
]}

Zhang, Xiaojian ^{[1
]}

Xue, Wenhua ^{[1
]}

Zhao, Songfeng ^{[1
]}

Zhang, Xiang ^{[1
]}

Pei, Jianying ^{[1
]}

机构：

[1] Zhengzhou Univ, Dept Pharm, Affiliated Hosp 1, Zhengzhou 450052, Peoples R China

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2014年 / 15卷 / 09期

关键词：

curcumin; gastric cancer; ROS; ASK1-MKK4-JNK; apoptosis; ENDOPLASMIC-RETICULUM STRESS; PANCREATIC-CANCER; CYTOCHROME-C; PROTEIN-KINASES; DOWN-REGULATION; IN-VITRO; ACTIVATION; MECHANISMS; GROWTH; CYCLE;

D O I：

10.3390/ijms150915754

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

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.

引用

页码：15754 / 15765

页数：12

共 49 条

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