PUBLICATION
Chiral ruthenium(II) complex Δ-[Ru(bpy)2(o-FMPIP)] (bpy = bipyridine, o-FMPIP = 2-(2'-trifluoromethyphenyl) imidazo[4,5-f][1,10]phenanthroline) as potential apoptosis inducer viaDNA damage
- Authors
- Bai, M., Pan, T., Yu, G., Xie, Q., Zeng, Z., Zhang, Y., Zhu, D., Mu, L., Qian, J., Chang, B., Mei, W.J., Guan, S.
- ID
- ZDB-PUB-190319-2
- Date
- 2019
- Source
- European Journal of Pharmacology 853: 49-55 (Journal)
- Registered Authors
- Keywords
- Angiogenesis, Apoptosis, Chiral ruthenium(II) complex, DNA Damage
- MeSH Terms
-
- Angiogenesis Inhibitors/chemistry
- Angiogenesis Inhibitors/pharmacology
- Angiogenesis Inhibitors/toxicity
- Animals
- Apoptosis/drug effects*
- DNA Damage*
- Dose-Response Relationship, Drug
- Hep G2 Cells
- Humans
- Mice
- Organometallic Compounds/chemistry*
- Organometallic Compounds/pharmacology*
- Organometallic Compounds/toxicity
- Phenanthrolines/chemistry*
- Pyridines/chemistry*
- Ruthenium/chemistry*
- Stereoisomerism
- Zebrafish
- PubMed
- 30880177 Full text @ Eur. J. Pharmacol.
Citation
Bai, M., Pan, T., Yu, G., Xie, Q., Zeng, Z., Zhang, Y., Zhu, D., Mu, L., Qian, J., Chang, B., Mei, W.J., Guan, S. (2019) Chiral ruthenium(II) complex Δ-[Ru(bpy)2(o-FMPIP)] (bpy = bipyridine, o-FMPIP = 2-(2'-trifluoromethyphenyl) imidazo[4,5-f][1,10]phenanthroline) as potential apoptosis inducer viaDNA damage. European Journal of Pharmacology. 853:49-55.
Abstract
Chiral ruthenium(II) complexes have long been considered as potential anticancer agents. Herein, in vivo inhibitory activity of a chiral ruthenium(II) complex coordinated by ligand 2-(2'-trifluoromethyphenyl) imidazo [4,5-f][1,10]phenanthroline, Δ-[Ru(bpy)2(o-FMPIP)] (D0402) on Kunming(KM) mice bearing tumor (H22 hepatic cancer) has been evaluated, and the results showed that the tumor weight of mice treated with 0.22mg/(kg·day) D0402 via i.v. administration for 7 days decreased about 31.79% compared to the control group, while the body weight, as well as the thymus, spleen, liver, lung, and kidney indices of mice treated with D0402 observed almost no loss compared to the control group. Furthermore, the mechanism studies on anti-angiogenic showed that D0402 could inhibit the formation of angiogenesis in the transgenic Tg(fli1a: EGFP) zebrafish. After treated with D0402, the sub-intestinal vessels(SIVs) of the zebrafish became disordered and chaotic, and was dosage dependent. Moreover, the TUNEL analysis and comet assays revealed that D0402 can induce apoptosis of HepG2 cell through DNA damage, and this was further demonstrated by immunofluorescence analysis with the number of γ-H2AX increased following the increasing amount of D0402. Besides, in vivo toxicity of D0402 has also been investigated on the development of zebrafish embryo, and the results showed that there were no death or development delay occurred for zebrafish embryo treated with D0402 up to concentration of 60μM. All in together, this study suggested that D0402 can be developed as a potential inhibitor against liver cancer through co-junction of anti-angiogenesis and apoptosis-inducing via DNA damage in the near future.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping