机构：[1]Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou510515, China[2]Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming 650032,Yunnan Province, China内科科室外科科室消化内科普通外科普通外一科(胃肠与疝外科)昆明医科大学附属第一医院省级研究所云南省消化疾病研究所
Withaferin A (WA) is an active steroidal lactone derived from the herbal plant Withania somnifera, which exhibits antitumor activity with reactive oxygen species (ROS) modulating in a variety of cancer models, such as breast cancer, lung cancer and pancreatic cancer. However, to the best of our knowledge, the direct effect and mechanism of WA on CRC cells has not been previously determined. The present study investigated the anti-tumor effects of WA on CRC cells in vitro, and explored the mechanisms of action. The flow cytometry was applied for detecting the accumulation of ROS with the treatment of withaferin A. We performed the flow cytometry and western blot to evaluate the withaferin A induced apoptosis and cell cycle arrest in human colon cancer cells. And to verify the ROS accumulation induced mitochondrial dysfunction after the treatment of withaferin A, fluorescence microscope and western blot were applied. WA exerted a dose-dependent cytotoxic effect on HCT-116 and RKO cells. The effect was associated with ROS-mediated cell cycle arrest and the expression of apoptotic proteins. In addition, WA promoted ROS production and decreased mitochondrial membrane potential accompanying with mitochondrial dysfunction. Taken together, these results strongly indicated that WA directly inhibits cell growth and induces apoptosis in CRC cells through ROS-mediated mitochondrial dysfunction and JNKs pathway, and WA may be a promising potential candidate for therapeutic application of CRC. (C) 2018 Elsevier Inc. All rights reserved.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81660100, 81670501]; Guangdong gastrointestinal disease research center [2017B02029003]; Guangzhou Pilot Project of Clinical and Translational Research Center [7415696196402]; Guangdong Provincial Bioengineering Research Center for Gastroenterology Diseases, Guangdong gastrointestinal disease research center; Applied Basic Research Key Projects of Yunnan Province [2016FA033]; Foundation of Yunnan Institute of Digestive Disease [2016NS002]; Digestive Disease Prevention and Treatment Engineering Research Center of Yunnan Province
第一作者机构：[1]Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou510515, China[2]Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming 650032,Yunnan Province, China
通讯作者：
推荐引用方式(GB/T 7714)：
Xia Shuxian,Miao Yinglei,Liu Side.Withaferin A induces apoptosis by ROS-dependent mitochondrial dysfunction in human colorectal cancer cells[J].BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.2018,503(4):2363-2369.doi:10.1016/j.bbrc.2018.06.162.
APA：
Xia, Shuxian,Miao, Yinglei&Liu, Side.(2018).Withaferin A induces apoptosis by ROS-dependent mitochondrial dysfunction in human colorectal cancer cells.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,503,(4)
MLA：
Xia, Shuxian,et al."Withaferin A induces apoptosis by ROS-dependent mitochondrial dysfunction in human colorectal cancer cells".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 503..4(2018):2363-2369
