PUBLICATION
Polypyridyl Ruthenium(II) complex-induced mitochondrial membrane potential dissipation activates DNA damage-mediated apoptosis to inhibit liver cancer
- Authors
- Li, Y., Wu, Q., Yu, G., Li, L., Zhao, X., Huang, X., Mei, W.
- ID
- ZDB-PUB-190102-4
- Date
- 2018
- Source
- European Journal of Medicinal Chemistry 164: 282-291 (Journal)
- Registered Authors
- Keywords
- Apoptosis, DNA damage, Liver cancer, Mitochondrial membrane potential, Polypyridyl ruthenium(II) complexes
- MeSH Terms
-
- Animals
- Antineoplastic Agents/chemical synthesis*
- Apoptosis/drug effects*
- Cell Line, Tumor
- Cell Proliferation/drug effects
- Coordination Complexes/chemical synthesis
- Coordination Complexes/chemistry
- Coordination Complexes/pharmacology*
- DNA Damage
- Hep G2 Cells
- Heterografts
- Humans
- Liver Neoplasms/drug therapy*
- Membrane Potential, Mitochondrial/drug effects
- Pyridines/chemistry
- Ruthenium/chemistry
- Zebrafish
- PubMed
- 30599417 Full text @ Eur. J. Med. Chem.
Citation
Li, Y., Wu, Q., Yu, G., Li, L., Zhao, X., Huang, X., Mei, W. (2018) Polypyridyl Ruthenium(II) complex-induced mitochondrial membrane potential dissipation activates DNA damage-mediated apoptosis to inhibit liver cancer. European Journal of Medicinal Chemistry. 164:282-291.
Abstract
In this study, four polypyridyl ruthenium(II) complexes, namely, [(L1)2RuL2]·2ClO4 (1: L1 = phen, L2 = o-TFPIP, 2: L1 = bpy, L2 = o-TFPIP, 3: L1 = phen, L2 = o-MOPIP, and 4: L1 = bpy, L2 = o-MOPIP), were synthesized with different phenanthroimidazole derivatives, and their inhibitory activities were tested against various cancer cells. Among the Ru(II) complexes, 1 excellently inhibited the proliferation and induced the apoptosis of HepG2 cell. Importantly, 1 was mainly distributed in the cell mitochondria and markedly induced the dissipation of mitochondrial membrane potential, possibly attributing to DNA damage induced by the Ru(II) complexes. Synthetic Ru(II) complexes can suppress the growth of tumor cells in zebrafish xenograft model with low toxicity at effective concentrations. These results inspired us to further develop polypyridyl ruthenium(II) complexes as potential potent inhibitors against liver cancer.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping