文献类型：期刊文献

英文题名：Assessment of the Cytotoxic and Apoptotic Effects of Chaetominine in a Human Leukemia Cell Line

作者：Yao, Jingyun[1,2];Jiao, Ruihua;Liu, Changqing[1,2];Zhang, Yupeng[1,2];Yu, Wanguo[1,2];Lu, Yanhua[1,2];Tan, Renxiang[3]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Shanghai Collaborat Innovat Ctr Biomfg Technol, Shanghai 200237, Peoples R China;[3]Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Inst Funct Biomol, Nanjing 210093, Jiangsu, Peoples R China

年份：2016

卷号：24

期号：2

起止页码：147

外文期刊名：BIOMOLECULES & THERAPEUTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000370892300006)】；

基金：This work was supported by the National High Technology Research and Development Program of China (2013AA092901), and partially financed by the Fundamental Research Funds for the Central Universities (WF1113010), the National Special Fund for State Key Laboratory of Bioreactor Engineering (2060204).

语种：英文

外文关键词：Cytotoxic; Apoptosis; Mitochondrial pathway; K562 cell

摘要：Chaetominine is a quinazoline alkaloid originating from the endophytic fungus Aspergillus fumigatus CY018. In this study, we showed evidence that chaetominine has cytotoxic and apoptotic effects on human leukemia K562 cells and investigated the pathway involved in chaetominine-induced apoptosis in detail. Chaetominine inhibited K562 cell growth, with an 1050 value of 35 nM, but showed little inhibitory effect on the growth of human peripheral blood mononuclear cells. The high apoptosis rates, morphological apoptotic features, and DNA fragmentation caused by chaetominine indicated that the cytotoxicity was partially caused by its pro-apoptotic effect. Under chaetominine treatment, the Bax/Bcl-2 ratio was upregulated (from 0.3 to 8), which was followed by a decrease in mitochondrial membrane potential, release of cytochrome c from mitochondria into the cytosol, and stimulation of Apaf-1. Furthermore, activation of caspase-9 and caspase-3, which are the main executers of the apoptotic process, was observed. These results demonstrated that chaetominine induced cell apoptosis via the mitochondrial pathway. Chaetominine inhibited K562 cell growth and induced apoptotic cell death through the intrinsic pathway, which suggests that chaetominine might be a promising therapeutic for leukemia.