Curcumin analog EF24 induces apoptosis via ROS-dependent mitochondrial dysfunction in human colorectal cancer cells

doi:10.1007/s00280-016-3172-x

科研成果详情

题名	Curcumin analog EF24 induces apoptosis via ROS-dependent mitochondrial dysfunction in human colorectal cancer cells
作者	He, Guodong1,2,3; Feng, Chen 1; Vinothkumar, Rajamanickam 1; Chen, Weiqian1; Dai, Xuanxuan1; Chen, Xi 1; Ye, Qingqing 1; Qiu, Chenyu1; Zhou, Huiping4; Wang, Yi1; Liang, Guang1; Xie, Yubo 3; Wu, Wei1,4
发表日期	2016-12
发表期刊	CANCER CHEMOTHERAPY AND PHARMACOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Curcumin analog EF24 Colorectal cancer ROS Mitochondrial dysfunction
其他关键词	ENDOPLASMIC-RETICULUM STRESS ; SP TRANSCRIPTION FACTORS ; SPECIFICITY PROTEINS SP ; GASTRIC-CANCER ; TUMOR-GROWTH ; CYCLE ARREST ; LUNG-CANCER ; ER STRESS ; PATHWAYS ; INHIBITOR
摘要	Purpose Colorectal cancer is the most commonly diagnosed malignancy with high mortality rates worldwide. Improved therapeutic strategies with minimal adverse side effects are urgently needed. In this study, the anti-tumor effects of EF24, a novel analog of the natural compound curcumin, were evaluated in colorectal cancer cells. Methods The anti-tumor activity of EF24 on human colon cancer lines (HCT-116, SW-620, and HT-29) was determined by measures of cell cycle arrest, apoptosis, and mitochondrial function. The contribution of ROS in the EF24-induced anti-tumor activity was evaluated by measures of H2O2 and pretreatment with an ROS scavenger, NAC. Results The findings indicated that EF24 treatment dose-dependently inhibited cell viability and caused cell cycle arrest at G2/M phase in all the tested colon cancer cell lines. Furthermore, we demonstrated that EF24 treatment induced apoptosis effectively via enhancing intracellular accumulation of ROS in both HCT-116 and SW-620 cells, but with moderate effects in HT-29 cells. We found that EF24 treatment decreased the mitochondrial membrane potential in the colon cancer cells, leading to the release of mitochondrial cytochrome c. Also, EF24 induced activation of caspases 9 and 3, causing decreased Bcl-2 protein expression and Bcl-2/Bax ratio. Pretreatment with NAC, a ROS scavenger, abrogated the EF24-induced cell death, apoptosis, cell cycle arrest, and mitochondrial dysfunction, suggesting an upstream ROS generation which was responsible for the anticancer effects of EF24. Conclusions Our findings support an anticancer mechanism by which EF24 enhanced ROS accumulation in colon cancer cells, thereby resulting in mitochondrial membrane collapse and activated intrinsic apoptotic signaling. Thus, EF24 could be a potential candidate for therapeutic application of colon cancer.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81572448, 81472307, 81560500, 81160289]
出版者	SPRINGER
出版地	NEW YORK
ISSN	0344-5704
EISSN	1432-0843
卷号	78 期号:6 页码:1151-1161
DOI	10.1007/s00280-016-3172-x
页数	11
WOS类目	Oncology ; Pharmacology & Pharmacy
WOS研究方向	Oncology ; Pharmacology & Pharmacy
WOS记录号	WOS:000392322300005
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	27787644
SCOPUSEID	2-s2.0-84992740314
通讯作者地址	[Wu, Wei]Department of Gastroenterology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325035,China
Scopus学科分类	Oncology;Toxicology;Pharmacology;Cancer Research;Pharmacology (medical)
引用统计	被引频次：55[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/3601
专题	药学院（分析测试中心）附属第一医院_麻醉科附属第一医院_消化内科
通讯作者	Wu, Wei
作者单位	1.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China; 2.Department of Anesthesiology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325035,China; 3.Department of Anesthesiology,The First Affiliated Hospital of Guangxi Medical University,Nanning,530021,China; 4.Department of Gastroenterology,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; 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; 麻醉科
通讯作者单位	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
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	He, Guodong,Feng, Chen,Vinothkumar, Rajamanickam,et al. Curcumin analog EF24 induces apoptosis via ROS-dependent mitochondrial dysfunction in human colorectal cancer cells[J]. CANCER CHEMOTHERAPY AND PHARMACOLOGY,2016,78(6):1151-1161.
APA	He, Guodong., Feng, Chen., Vinothkumar, Rajamanickam., Chen, Weiqian., Dai, Xuanxuan., ... & Wu, Wei. (2016). Curcumin analog EF24 induces apoptosis via ROS-dependent mitochondrial dysfunction in human colorectal cancer cells. CANCER CHEMOTHERAPY AND PHARMACOLOGY, 78(6), 1151-1161.
MLA	He, Guodong,et al."Curcumin analog EF24 induces apoptosis via ROS-dependent mitochondrial dysfunction in human colorectal cancer cells".CANCER CHEMOTHERAPY AND PHARMACOLOGY 78.6(2016):1151-1161.