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  3. Mitochondria-Accumulating Rhenium(I) Tricarbonyl Complexes Induce Cell Death via Irreversible Oxidative Stress and Glutathione Metabolism Disturbance

Mitochondria-Accumulating Rhenium(I) Tricarbonyl Complexes Induce Cell Death via Irreversible Oxidative Stress and Glutathione Metabolism Disturbance

  • ACS Appl Mater Interfaces. 2019 Apr 10;11(14):13123-13133. doi: 10.1021/acsami.9b01057.
Fang-Xin Wang 1,  Jin-Hao Liang 1,  Hang Zhang 1,  Ze-Hua Wang 1,  Qin Wan 1,  Cai-Ping Tan 1,  Liang-Nian Ji 1,  Zong-Wan Mao 1
Affiliations

Affiliation

  • 1 MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry , Sun Yat-Sen University , Guangzhou 510275 , P. R. China.
PMID: 30888144 DOI: 10.1021/acsami.9b01057
Abstract

Mitochondria play a critical role in tumorigenesis. Targeting mitochondria and disturbing related events have been emerging as a promising way for chemotherapy. In this work, two binuclear rhenium(I) tricarbonyl complexes of the general formula [Re2(CO)6(dip)2L](PF6)2 (dip = 4,7-diphenyl-1,10-phenanthroline; L = 4,4'-azopyridine (ReN) or 4,4'-dithiodipyridine (ReS)) were synthesized and characterized. ReN and ReS can react with glutathione (GSH). They exhibit good in vitro Anticancer activity against Cancer cell lines screened. Besides, they can target mitochondria, cause oxidative stress, and disturb GSH metabolism. Both ReN and ReS can induce Necroptosis and caspase-dependent Apoptosis simultaneously. We also demonstrate that ReN and ReS can inhibit tumor growth in nude mice bearing carcinoma xenografts. Our study shows the potential of Re(I) complexes as chemotherapeutic agents to kill Cancer cells via a mitochondria-to-cellular redox strategy.

Keywords

apoptosis; glutathione metabolism; mitochondrial dysfunction; necroptosis; oxidative stress; rhenium(I) complexes.

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