文献类型：期刊文献

英文题名：Avermectin Confers Its Cytotoxic Effects by Inducing DNA Damage and Mitochondria-Associated Apoptosis

作者：Zhang, Yang[1];Luo, Mingming[1];Xu, Wenping[1];Yang, Mingjun[1];Wang, Bo[1];Gao, Jufang[2];Li, Yaxiao[3];Tao, Liming[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[2]Shanghai Normal Univ, Coll Life & Environm Sci, Shanghai 200234, Peoples R China;[3]Univ Bath, Dept Biol & Biochem, Claverton Down, Bath BA2 7AY, Avon, England

年份：2016

卷号：64

期号：36

起止页码：6895

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;EI(收录号：20163902832875);WOS:【SCI-EXPANDED(收录号:WOS:000383409600012)】；

基金：This work was financially supported by the National Key Technology Research Development Program of China (No. 2011BAE06B04).

语种：英文

外文关键词：avermectin; cytotoxic effects; DNA damage; apoptosis; mitochondrial pathway

摘要：Avermectin (AVM) has been widely used in agriculture and animal husbandry on the basis of its broad spectrum of effective anthelmintic activity and specificity targets. However, AVM induction of cytotoxicity through DNA damage is remains elusive. Here we investigate the cytotoxic effects of AVM in human nontarget cells in vitro. We clarify that AVM inhibited the viability of HeLa cells and enhanced apoptosis. We have used alkaline comet assay and gamma H2AX foci formation to detect DNA damage of HeLa cells. As expected, we found AVM caused DNA double-strand breaks in HeLa cells, as measured by significance of comet assay parameters (e.g., tail DNA) and increases of gamma H2AX foci in HeLa cells. Moreover, established assays of cytotoxicity were performed to characterize the mechanism of AVM toxicity on HeLa cells. The results demonstrated the collapse of mitochondrial membrane potential, and up-regulating the expression level of Bax/Bcl-2 resulted in a release of cytochrome c into cytosol as well as the activation of caspase-9/-3 and cleavage of poly(ADP-ribose) polymerase (PARP). We conclude that AVM has a potential risk to human health by inducing human cell DNA damage and mitochondria-associated apoptosis.