Yun Xinming, Rao Wenbing, Xiao Ciying, Huang Qingchun
Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
Environ Toxicol Pharmacol. 2017 Jun;52:280-287. doi: 10.1016/j.etap.2017.04.013. Epub 2017 Apr 19.
Leukemia threatens millions of people's health and lives, and the pesticide-induced leukemia has been increasingly concerned because of the etiologic exposure. In this paper, cytotoxic effect of emamectin benzoate (EMB), an excellent natural-product insecticide, was evaluated through monitoring cell viability, cell apoptosis, mitochondrial membrane potential and intracellular Ca concentration ([Ca]) in leukemia K562 and Molt-4 cells. Following the exposure to EMB, cell viability was decreased and positive apoptosis of K562 and Molt-4 cells was increased in a concentration- and time- dependent fashion. In the treatment of 10μM EMB, apoptotic cells accounted for 93.0% to K562 cells and 98.9% to Molt-4 cells based on the control, meanwhile, 63.47% of K562 cells and 81.15% of Molt-4 cells exhibited late apoptotic and necrotic features with damaged cytoplasmic membrane. 48h exposure to 10μM EMB increased significantly the great number of cells with mitochondrial membrane potential (MMP) loss, and the elevation of [Ca] level was peaked and persisted within 70s in K562 cells whilst 50s in Molt-4 cells. Moreover, a stronger cytotoxicity of EMB was further observed than that of imatinib. The results authenticate the efficacious effect of EMB as a potential anti-leukemia agent and an inconsistency with regard to insecticide-induced leukemia.
白血病威胁着数百万人的健康和生命，而农药诱发的白血病因其病因暴露而日益受到关注。本文通过监测白血病K562和Molt-4细胞的细胞活力、细胞凋亡、线粒体膜电位和细胞内钙浓度（[Ca]），评估了一种优秀的天然产物杀虫剂甲氨基阿维菌素苯甲酸盐（EMB）的细胞毒性作用。暴露于EMB后，K562和Molt-4细胞的细胞活力降低，阳性凋亡呈浓度和时间依赖性增加。在10μM EMB处理下，基于对照，K562细胞的凋亡细胞占93.0%，Molt-4细胞的凋亡细胞占98.9%，同时，63.47%的K562细胞和81.15%的Molt-4细胞表现出晚期凋亡和坏死特征，细胞膜受损。暴露于10μM EMB 48小时后，线粒体膜电位（MMP）丧失的细胞数量显著增加，K562细胞中[Ca]水平升高在70秒内达到峰值并持续，而Molt-4细胞中则在50秒内达到峰值并持续。此外，观察到EMB的细胞毒性比伊马替尼更强。结果证实了EMB作为一种潜在抗白血病药物的有效作用，以及与杀虫剂诱发白血病的不一致性。
