ROS generation mediates the anti-cancer effects of WZ35 via activating JNK and ER stress apoptotic pathways in gastric cancer

doi:10.18632/oncotarget.3333

科研成果详情

题名	ROS generation mediates the anti-cancer effects of WZ35 via activating JNK and ER stress apoptotic pathways in gastric cancer
作者	Zou, Peng1,2; Zhang, Junru 1; Xia, Yiqun3; Kanchana, Karvannan 1; Guo, Guilong4; Chen, Wenbo 1; Huang, Yi 1; Wang, Zhe1; Yang, Shulin 2; Liang, Guang1
发表日期	2015-03-20
发表期刊	ONCOTARGET 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Gastric cancer ROS Curcumin analog ER stress JNK
其他关键词	I CLINICAL-TRIAL ; PHASE-III ; CURCUMIN ANALOGS ; CELL-DEATH ; INDUCTION ; CISPLATIN ; MECHANISM ; CHOP ; 5-FLUOROURACIL ; OSTEOSARCOMA
摘要	Gastric cancer is one of the leading causes of cancer mortality in the world, and finding novel agents and strategies for the treatment of advanced gastric cancer is of urgent need. Curcumin is a well-known natural product with anti-cancer ability, but is limited by its poor chemical stability. In this study, an analog of curcumin with high chemical stability, WZ35, was designed and evaluated for its anti-cancer effects and underlying mechanisms against human gastric cancer. WZ35 showed much stronger anti-proliferative effects than curcumin, accompanied by dose-dependent induction of cell cycle arrest and apoptosis in gastric cancer cells. Mechanistically, our data showed that WZ35 induced reactive oxygen species (ROS) production, resulting in the activation of both JNK-mitochondrial and ER stress apoptotic pathways and eventually cell apoptosis in SGC-7901 cells. Blockage of ROS production totally reversed WZ35-induced JNK and ER stress activation as well as cancer cell apoptosis. In vivo, WZ35 showed a significant reduction in SGC-7901 xenograft tumor size in a dose-dependent manner. Taken together, this work provides a novel anticancer candidate for the treatment of gastric cancer, and importantly, reveals that increased ROS generation might be an effective strategy in human gastric cancer treatment.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81270489, 81302642]; Zhejiang Province Natural Science Funding of China [LY13H160022, LY12H16003]; Technology Foundation for Medical Science of Zhejiang Province [2012KYA129]; Zhejiang Provincial Project of Protein Medicine Key Group [2010R50042]
出版者	IMPACT JOURNALS LLC
出版地	ORCHARD PARK
ISSN	1949-2553
EISSN	1949-2553
卷号	6 期号:8 页码:5860-5876
DOI	10.18632/oncotarget.3333
页数	17
WOS类目	Oncology ; Cell Biology
WOS研究方向	Oncology ; Cell Biology
WOS记录号	WOS:000352793000028
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	25714022
PMC记录号	PMC4467407
SCOPUSEID	2-s2.0-84925637189
通讯作者地址	[Liang, Guang]Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou, Zhejiang,China
Scopus学科分类	Oncology
引用统计	被引频次：105[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/3333
专题	药学院（分析测试中心）附属第一医院_肿瘤外科第一临床医学院（信息与工程学院）、附属第一医院_内科学_消化内科
通讯作者	Liang, Guang
作者单位	1.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou, Zhejiang,China; 2.School of Environmental and Biological Engineering,Nanjing University of Science and Technology,Nanjing, Jiangsu,China; 3.Department of Digestive Diseases,The First Affiliated Hospital,Wenzhou Medical University,Wenzhou, Zhejiang,China; 4.Department of Oncological Surgery,The First Affiliated Hospital,Wenzhou Medical University,Wenzhou, Zhejiang,China
第一作者单位	药学院（分析测试中心）; 生物有机与药物化学研究中心
通讯作者单位	药学院（分析测试中心）; 生物有机与药物化学研究中心
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Zou, Peng,Zhang, Junru,Xia, Yiqun,et al. ROS generation mediates the anti-cancer effects of WZ35 via activating JNK and ER stress apoptotic pathways in gastric cancer[J]. ONCOTARGET,2015,6(8):5860-5876.
APA	Zou, Peng., Zhang, Junru., Xia, Yiqun., Kanchana, Karvannan., Guo, Guilong., ... & Liang, Guang. (2015). ROS generation mediates the anti-cancer effects of WZ35 via activating JNK and ER stress apoptotic pathways in gastric cancer. ONCOTARGET, 6(8), 5860-5876.
MLA	Zou, Peng,et al."ROS generation mediates the anti-cancer effects of WZ35 via activating JNK and ER stress apoptotic pathways in gastric cancer".ONCOTARGET 6.8(2015):5860-5876.