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Photoinduced anticancer activity studies of iridium(III) complexes targeting mitochondria and tubules.
- Source :
-
European Journal of Medicinal Chemistry . May2018, Vol. 151, p568-584. 17p. - Publication Year :
- 2018
-
Abstract
- Three new iridium (III) complexes [Ir (ppy) 2 (ipbc)](PF 6 ) ( 1 ), [Ir (bzq) 2 (ipbc)](PF 6 ) ( 2 ) and [Ir (piq) 2 (ipbc)](PF 6 ) ( 3 ) were designed and synthesized. All the complexes were tested for anticancer activity using 3-(4,5-dimethylthiazole)-2,5-diphenyltetraazolium bromide (MTT) method. The complexes show no cytotoxic activity toward cancer BEL-7402, SGC-7901, Eca-109, A549, HeLa and HepG2 cells. However, upon irradiation with white light, the complexes display high cytotoxicity against BEL-7402 cells with an IC 50 value of 5.5 ± 0.8, 7.3 ± 1.3 and 11.5 ± 1.6 μM for 1 , 2 and 3 , respectively. AO/EB staining and comet assay show that the complexes can induce apoptosis in BEL-7402 cells. The complexes can increase intracellular ROS and Ca 2+ levels and cause a decrease in the mitochondrial membrane potential. Autophagic assays exhibit that the complexes can induce autophagy and regulate the expression of Beclin-1 and LC3 proteins. The cell cycle distribution in BEL-7402 cells was carried out by flow cytometry. The expression of Bcl-2 family proteins was studied by western blot. Additionally, the complexes can release cytochrome c and inhibit the polymerization of α-tubulin. Our study reveals that the complexes inhibit the cell growth in BEL-7402 cells through an ROS-mediated mitochondria dysfunction and targeting tubules pathways. These complexes are a promising new entity for the development of multi-target anticancer drugs. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02235234
- Volume :
- 151
- Database :
- Academic Search Index
- Journal :
- European Journal of Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 129274344
- Full Text :
- https://doi.org/10.1016/j.ejmech.2018.04.013