Mitochondria Are the Primary Target in the Induction of Apoptosis by Chiral Ruthenium(II) Polypyridyl Complexes in Cancer Cells

Overview

Journal J Biol Inorg Chem

Publisher Springer

Specialty Biochemistry

Date 2013 Nov 30

PMID 24287874

Citations 17

Authors

Jin-Quan Wang

Ping-Yu Zhang

Chen Qian

Xiao-Juan Hou

Liang-Nian Ji

Hui Chao

Affiliations

Soon will be listed here.

Abstract

A series of novel chiral ruthenium(II) polypyridyl complexes (Δ-Ru1, Λ-Ru1, Δ-Ru2, Λ-Ru2, Δ-Ru3, Λ-Ru3) were synthesized and evaluated to determine their antiproliferative activities. Colocalization, inductively coupled plasma mass spectrometry, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay studies showed that these ruthenium(II) complexes accumulated preferentially in the mitochondria and exhibited cytotoxicity against various cancer cells in vitro. The complex Δ-Ru1 is of particular interest because it was found to have half-maximal inhibitory concentrations comparable to those of cisplatin and better activity than cisplatin against a cisplatin-resistant cell line, A549-CP/R. Δ-Ru1 induced alterations in the mitochondrial membrane potential and triggered intrinsic mitochondria-mediated apoptosis in HeLa cells, which involved the regulation of Bcl-2 family members and the activation of caspases. Taken together, these data suggest that Δ-Ru1 may be a novel mitochondria-targeting anticancer agent.

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