Restraining Cancer Cells by Dual Metabolic Inhibition with a Mitochondrion-Targeted Platinum(II) Complex

被引：151

作者：

Wang, Kun ^{[1
]}

Zhu, Chengcheng ^{[1
]}

He, Yafeng ^{[1
]}

Zhang, Zhenqin ^{[1
]}

Zhou, Wen ^{[1
]}

Muhammad, Nafees ^{[1
]}

Guo, Yan ^{[1
]}

Wang, Xiaoyong ^{[2
]}

Guo, Zijian ^{[1
]}

机构：

[1] Nanjing Univ, Sch Chem & Chem Engn, State Key Lab Coordinat Chem, Nanjing 210023, Jiangsu, Peoples R China

[2] Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210023, Jiangsu, Peoples R China

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2019年 / 58卷 / 14期

基金：

中国国家自然科学基金;

关键词：

antitumor agents; metabolism; mitochondria; platinum; thioredoxin reductase; THIOREDOXIN REDUCTASE; CISPLATIN; ANTIOXIDANTS; SYSTEM;

D O I：

10.1002/anie.201900387

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：4638 / 4643

页数：6

共 40 条

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