Curcuminoid WZ26, a TrxR1 inhibitor, effectively inhibits colon cancer cell growth and enhances cisplatin-induced cell death through the induction of ROS

doi:10.1016/j.freeradbiomed.2019.06.005

科研成果详情

题名	Curcuminoid WZ26, a TrxR1 inhibitor, effectively inhibits colon cancer cell growth and enhances cisplatin-induced cell death through the induction of ROS
作者	Zhang, Tingting1; Zheng, Peisen1; Shen, Xin1; Shao, Rongrong 1; Wang, Bin 1; Shen, Huanpei1; Zhang, Jingjing 1; Xia, Yiqun2; Zou, Peng1
发表日期	2019-09
发表期刊	FREE RADICAL BIOLOGY AND MEDICINE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Thioredoxin reductase 1 Reactive oxygen species WZ26 Cisplatin Colon cancer
其他关键词	SMALL-MOLECULE INHIBITORS ; THIOREDOXIN REDUCTASE ; MEDIATED MECHANISMS ; ACTIVATION ; RESISTANCE ; TOXICITY ; STRESS ; GLUTATHIONE ; EXPRESSION ; APOPTOSIS
摘要	Colon cancer is one of the leading causes of cancer-related deaths. Chemotherapy has improved survival in patients with colon cancer, but has a narrow therapeutic window due to its toxicity. Therefore, novel therapies for colon cancer are urgently needed. We previously developed a curcumin analog WZ26 as an anti-cancer agent in pre-clinical evaluation. In the present study, we further explored the mechanism and target of WZ26 in colon cancer cells. Our results show that WZ26 targets thioredoxin reductase 1 (TrxR1) and increases cellular reactive oxygen species (ROS) levels, which results in the activation of JNK signaling pathway in human colon cancer cells. Furthermore, we found that WZ26 significantly enhances cisplatin-induced cell growth inhibition in colon cancer cells. WZ26 combined with cisplatin markedly increases the accumulation of ROS, and thereby induces DNA damage and activation of JNK signaling pathway. Pretreatment with antioxidant N-acetyl-L-cysteine (NAC) significantly abrogates the combined treatment-induced ROS generation, DNA damage and cell death. In addition, the activation of JNK signaling pathway prompted by WZ26 and cisplatin was also reversed by NAC pretreatment. In vivo, WZ26 combined with cisplatin significantly inhibits tumor growth in a colon cancer xenograft model. Remarkably, WZ26 attenuates the body weight loss evoked by cisplatin treatment. This study discloses a previously unrecognized mechanism underlying the biological activity of WZ26, and reveals that WZ26 and cisplatin combinational treatment might potentially become a more effective regimen in colon cancer therapy.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81603153, 81503107]; National College Students Innovation and Entrepreneurship Training Program [201810343018]; Zhejiang Provincial College Students' Technological Innovation Training Program [2018R413042]; Zhejiang Provincial Natural Science FoundationNatural Science Foundation of Zhejiang Province [LY16H310011]
出版者	ELSEVIER SCIENCE INC
出版地	NEW YORK
ISSN	0891-5849
EISSN	1873-4596
卷号	141 页码:93-102
DOI	10.1016/j.freeradbiomed.2019.06.005
页数	10
WOS类目	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS研究方向	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS记录号	WOS:000483920100009
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
Pubmed记录号	31176737
Scopus记录号	2-s2.0-85067055953
通讯作者地址	[Zou, Peng]Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China
scopus学科分类	Biochemistry;Physiology (medical)
引用统计	被引频次：22[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/12445
专题	药学院（分析测试中心）_生物有机与药物化学研究中心附属第一医院第一临床医学院（信息与工程学院）、附属第一医院_内科学_消化内科
通讯作者	Zou, Peng
作者单位	1.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China; 2.Department of Digestive Diseases,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325035,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	Zhang, Tingting,Zheng, Peisen,Shen, Xin,et al. Curcuminoid WZ26, a TrxR1 inhibitor, effectively inhibits colon cancer cell growth and enhances cisplatin-induced cell death through the induction of ROS[J]. FREE RADICAL BIOLOGY AND MEDICINE,2019,141:93-102.
APA	Zhang, Tingting., Zheng, Peisen., Shen, Xin., Shao, Rongrong., Wang, Bin., ... & Zou, Peng. (2019). Curcuminoid WZ26, a TrxR1 inhibitor, effectively inhibits colon cancer cell growth and enhances cisplatin-induced cell death through the induction of ROS. FREE RADICAL BIOLOGY AND MEDICINE, 141, 93-102.
MLA	Zhang, Tingting,et al."Curcuminoid WZ26, a TrxR1 inhibitor, effectively inhibits colon cancer cell growth and enhances cisplatin-induced cell death through the induction of ROS".FREE RADICAL BIOLOGY AND MEDICINE 141(2019):93-102.