Antimony exposure promotes bladder tumor cell growth by inhibiting PINK1-Parkin-mediated mitophagy

作者：Yantao Lou, Chunlei Ma, Zhifei Liu, Jianxi Shi, Guangzhe Zheng, Changwen Zhang, Zhihong Zhang · 发表于：Ecotoxicology and Environmental Safety · 年份：2021 · DOI：10.1016/j.ecoenv.2021.112420 · 被引用次数：28 · 研究领域：Arsenic contamination and mitigation、Ferroptosis and cancer prognosis、Folate and B Vitamins Research

Antimony is one of the heavier pnictogens and is widely found in human food chains, water sources, and as an air pollutant. Recent years have seen steadily increasing concentrations of antimony in the ecological environment; critically, several studies have indicated that antimony might pose a tumorigenic risk factor in several cancers. Therefore, antimony toxicity has attracted increasing research attention, with the molecular mechanisms underlying suspected antimony-mediated tumor transformation of greatest interest. Our results showed that the serum concentration of antimony was higher in bladder tumor patients relative to levels in non-tumor patients. Moreover, that such high antimony serum concentration were closely associated with poorer outcome in bladder tumor patients. Additionally, we demonstrated that the presence of antimony promoted both in vitro and in vivo bladder tumor cell growth. Our results also indicated that low-dose antimony resulted in significantly decreased mitochondrial membrane potential, mitochondrial respiratory enzyme complex I/II/III/IV activity, ATP/ADP ratio, and ATP concentration relative to the control group. These findings suggested that antimony caused mitochondrial damage. Finally, we found that low-dose antimony(0.8uM) inhibited mitophagy by deregulating expression of PINK1, Parkin, and p(ser65)-Parkin, and activation of PINK1-Parkin pathway by CCCP could inhibit antimony-induced tumor cell growth. Collectively, this inhibited the prolif...