硫氧还蛋白还原酶
癌细胞
生物能学
线粒体
活性氧
细胞毒性
化学
细胞生物学
顺铂
硫氧还蛋白
糖酵解
癌症
癌症研究
细胞凋亡
生物
生物化学
新陈代谢
酶
体外
遗传学
化疗
作者
Kun Wang,Chengcheng Zhu,Yafeng He,Zhenqin Zhang,Wen Zhou,Muhammad Nafees,Yan Guo,Xiaoyong Wang,Zijian Guo
标识
DOI:10.1002/anie.201900387
摘要
Abstract Cancer cells usually adapt metabolic phenotypes to chemotherapeutics. A defensive strategy against this flexibility is to modulate signaling pathways relevant to cancer bioenergetics. A triphenylphosphonium‐modified terpyridine platinum(II) complex (TTP) was designed to inhibit thioredoxin reductase (TrxR) and multiple metabolisms of cancer cells. TTP exhibited enhanced cytotoxicity against cisplatin‐insensitive human ovarian cancer cells in a caspase‐3‐independent manner and showed preferential inhibition to mitochondrial TrxR. The morphology and function of mitochondria were severely damaged, and the levels of mitochondrial and cellular reactive oxygen species were decreased. As a result, TTP exerted strong inhibition to both mitochondrial and glycolytic bioenergetics, thus inducing cancer cells to enter a hypometabolic state.
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