Yu Xiaoqin, Zhang Yang, Yang Mingjun, Guo Junfu, Xu Wenping, Gao Jufang, Li Yaxiao, Tao Liming
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
College of Life and Environmental Sciences, Shanghai Normal University, Shanghai 200234, China.
Ecotoxicol Environ Saf. 2016 Jul;129:180-8. doi: 10.1016/j.ecoenv.2016.03.025. Epub 2016 Apr 1.
Tebufenozide is considered an environmentally friendly pesticide due to its specificity on target insects, but the effects on human are well studied. Studies on the toxicity of tebufenozide at molecular and cellular level is poorly understood. The present study reveals non-selective cytotoxic effects of tebufenozide, and the apoptotic mechanism induced by tebufenozide on HeLa and Tn5B1-4 cells. We demonstrate that the viability of HeLa and Tn5B1-4 cells is inhibited by tebufenozide in a time- and concentration-dependent manner. Intracellular biochemical assays showed that tebufenozide-induced apoptosis of two cell lines concurrent with a decrease in the mitochondrial membrane potential and an increase reactive oxygen species generation, the release of cytochrome-c into the cytosol and a marked activation of caspase-3. These results indicate that a mitochondrial-dependent intrinsic pathway contributes to tebufenozide induced apoptosis in HeLa and Tn5B1-4 cells and suggests potential threats to ecosystems and human health.
虫酰肼因其对目标昆虫的特异性而被认为是一种环境友好型农药,但对人体的影响已有充分研究。关于虫酰肼在分子和细胞水平上的毒性研究了解甚少。本研究揭示了虫酰肼的非选择性细胞毒性作用,以及虫酰肼诱导HeLa和Tn5B1-4细胞凋亡的机制。我们证明,虫酰肼以时间和浓度依赖性方式抑制HeLa和Tn5B1-4细胞的活力。细胞内生化分析表明,虫酰肼诱导两种细胞系凋亡,同时线粒体膜电位降低,活性氧生成增加,细胞色素c释放到细胞质中,半胱天冬酶-3显著激活。这些结果表明,线粒体依赖性内在途径促成了虫酰肼诱导HeLa和Tn5B1-4细胞凋亡,并提示对生态系统和人类健康存在潜在威胁。