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

Author(s) Wang, F.X.; Liang, J.H.; Zhang, H.; Wang, Z.H.; Wan, Q.; Tan, C.P.; Ji, L.N.; Mao, Z.W.
Journal ACS Appl Mater Interfaces
Date Published 2019 Apr 10
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 [Re(CO)(dip)L](PF) (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.

DOI 10.1021/acsami.9b01057
ISSN 1944-8252
Citation Wang F-, Liang J-, Zhang H, Wang Z-, Wan Q, Tan C-, et al. Mitochondria-Accumulating Rhenium(I) Tricarbonyl Complexes Induce Cell Death via Irreversible Oxidative Stress and Glutathione Metabolism Disturbance. ACS Appl Mater Interfaces. 2019;11(14):13123-13133.