Novel allylated monocarbonyl analogs of curcumin induce mitotic arrest and apoptosis by reactive oxygen species-mediated endoplasmic reticulum stress and inhibition of STAT3

doi:10.18632/oncotarget.20924

科研成果详情

题名	Novel allylated monocarbonyl analogs of curcumin induce mitotic arrest and apoptosis by reactive oxygen species-mediated endoplasmic reticulum stress and inhibition of STAT3
作者	Rajamanickam, Vinothkumar 1; Zhu, Heping 1; Feng, Chen 1; Chen, Xi 1; Zheng, Hailun1; Xu, Xiaohong 1; Zhang, Qianqian 1,2; Zou, Peng1; He, Guodong1,3; Dai, Xuanxuan1,4; Yang, Xi1,5; Wang, Yi1; Liu, Zhiguo1; Liang, Guang1; Guo, Guilong1,4
发表日期	2017-11-24
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 curcumin analog reactive oxygen species ER stress pSTAT3
其他关键词	MONO-CARBONYL ANALOGS ; CELL-CYCLE ARREST ; ER STRESS ; OXIDATIVE STRESS ; CANCER-CELLS ; BIOLOGICAL EVALUATION ; ROS GENERATION ; GASTRIC-CANCER ; IN-VITRO ; PATHWAYS
摘要	Curcumin is a promising active compound from a natural source and is extensively being tested in clinical trials because of its bio-functional properties. However, poor bioavailability has hampered its clinical application. Numerous attempts have been made in our laboratory to discover analogs of curcumin with enhanced bioavailability and superior pharmacological activity. In this study, we have investigated a new series of allylated monocarbonyl analogs of curcumin (MAC) and tested their effect on gastric cancer cells. Our results show six MAC that selectively targeted cancer cell lines to inhibit growth and induce apoptosis. This activity was achieved by generation of reactive oxygen species (ROS) by MAC. We selected one effective MAC (CA10) for further investigation and show that CA10 inhibits cell growth by causing G2/M cell cycle arrest and induction of apoptotic death. CA10 induced ROS generation and subsequent activation of endoplasmic reticulum (ER) stress and inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation, inhibits cancer cell proliferation. These anti-tumor activities of CA10 were confirmed in gastric cancer xenografts. CA10 induced ROS, activated the ER stress pathway and inhibited STAT3 phosphorylation and gastric xenografts tumor growth in mice. Our studies provide experimental evidence that MAC CA10 effectively targets gastric cancer in preclinical models by enhancing ROS and ROS-mediated signaling.
资助项目	National Natural Science Funding of ChinaNational Natural Science Foundation of China (NSFC) [81472307, 81622043, 81503107]; Zhejiang Province Natural Science Funding [LYI6H160050, LY17H160055, LY17B020008, R18H160006]
出版者	IMPACT JOURNALS LLC
出版地	ORCHARD PARK
ISSN	1949-2553
EISSN	1949-2553
卷号	8 期号:60 页码:101112-101129
DOI	10.18632/oncotarget.20924
页数	18
WOS类目	Oncology ; Cell Biology
WOS研究方向	Oncology ; Cell Biology
WOS记录号	WOS:000419533200013
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	29254150
PMC记录号	PMC5731860
SCOPUSEID	2-s2.0-85034847873
通讯作者地址	[Liang, Guang]Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China
Scopus学科分类	Oncology
引用统计	被引频次：18[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/11942
专题	药学院（分析测试中心）附属第一医院眼视光学院（生物医学工程学院）、附属眼视光医院其他_附属第五医院（丽水市中心医院）
通讯作者	Liang, Guang
作者单位	1.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China; 2.Department of Interventional Radiology,The Fifth Affiliated Hospital of Wenzhou Medical University,Lishui, Zhejiang,323000,China; 3.Department of Anesthesiology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou, Zhejiang,325035,China; 4.Department of Surgical Oncology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou, Zhejiang,325035,China; 5.The Eye Hospital of Wenzhou Medical University,Wenzhou, Zhejiang,325027,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	Rajamanickam, Vinothkumar,Zhu, Heping,Feng, Chen,et al. Novel allylated monocarbonyl analogs of curcumin induce mitotic arrest and apoptosis by reactive oxygen species-mediated endoplasmic reticulum stress and inhibition of STAT3[J]. ONCOTARGET,2017,8(60):101112-101129.
APA	Rajamanickam, Vinothkumar., Zhu, Heping., Feng, Chen., Chen, Xi., Zheng, Hailun., ... & Guo, Guilong. (2017). Novel allylated monocarbonyl analogs of curcumin induce mitotic arrest and apoptosis by reactive oxygen species-mediated endoplasmic reticulum stress and inhibition of STAT3. ONCOTARGET, 8(60), 101112-101129.
MLA	Rajamanickam, Vinothkumar,et al."Novel allylated monocarbonyl analogs of curcumin induce mitotic arrest and apoptosis by reactive oxygen species-mediated endoplasmic reticulum stress and inhibition of STAT3".ONCOTARGET 8.60(2017):101112-101129.