1. Mitochondria are the primary target in the induction of apoptosis by chiral ruthenium(II) polypyridyl complexes in cancer cells.
- Author
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Wang JQ, Zhang PY, Qian C, Hou XJ, Ji LN, and Chao H
- Subjects
- Antineoplastic Agents chemistry, Apoptosis physiology, Cell Line, Tumor, HeLa Cells, Hep G2 Cells, Humans, MCF-7 Cells, Membrane Potential, Mitochondrial drug effects, Membrane Potential, Mitochondrial physiology, Mitochondria pathology, Pyridines chemistry, Ruthenium chemistry, Antineoplastic Agents administration & dosage, Apoptosis drug effects, Drug Delivery Systems methods, Mitochondria drug effects, Pyridines administration & dosage, Ruthenium administration & dosage
- 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.
- Published
- 2014
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