Design, Synthesis, and Anticancer Effect Studies of Iridium(III) Polypyridyl Complexes against SGC-7901 Cells
| Autor: | Lan Bai, Yun-Jun Liu, Fan Du, Yan-Zhong Chen, Miao He, Yang-Jie Wang, Wen-Yao Zhang, Li-Xia Zhang, Yi-Ying Gu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Cell cycle checkpoint
Pyridines Pharmaceutical Science Iridium 01 natural sciences Analytical Chemistry Metastasis HeLa Mice Coordination Complexes Drug Discovery biology Chemistry apoptosis Hep G2 Cells medicine.anatomical_structure Chemistry (miscellaneous) Molecular Medicine iridium(III) complexes Cell Survival DNA damage 010402 general chemistry Article 3T3 cells lcsh:QD241-441 Inhibitory Concentration 50 lcsh:Organic chemistry Stomach Neoplasms Cell Line Tumor mitochondrial dysfunction medicine Animals Humans antitumor activity Physical and Theoretical Chemistry Cell Proliferation 010405 organic chemistry Cell growth Organic Chemistry biology.organism_classification medicine.disease Molecular biology In vitro 0104 chemical sciences A549 Cells Apoptosis Drug Design NIH 3T3 Cells Drug Screening Assays Antitumor Reactive Oxygen Species HeLa Cells |
| Zdroj: | Molecules, Vol 24, Iss 17, p 3129 (2019) Molecules Volume 24 Issue 17 |
| ISSN: | 1420-3049 |
| Popis: | Three iridium(III) complexes ([Ir(Hppy)2(L)](PF6) (Hppy = 2-phenylpyridine, L = 5-nitrophenanthroline, NP), 1 5-nitro-6-amino-phenanthroline (NAP), 2 and 5,6-diamino-phenanthroline (DAP) 3 were synthesized and characterized. The cytotoxicities of Ir(III) complexes 1&ndash 3 against cancer cell lines SGC-7901, A549, HeLa, Eca-109, HepG2, BEL-7402, and normal NIH 3T3 cells were investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) method. The results showed that the three iridium(III) complexes had moderate in vitro anti-tumor activity toward SGC-7901 cells with IC50 values of 3.6 ± 0.1 µ M for 1, 14.1 ± 0.5 µ M for 2, and 11.1 ± 1.3 µ M for 3. Further studies showed that 1&ndash 3 induce cell apoptosis/death through DNA damage, cell cycle arrest at the S or G0/G1 phase, ROS elevation, increased levels of Ca2+, high mitochondrial membrane depolarization, and cellular ATP depletion. Transwell and Colony-Forming assays revealed that complexes 1&ndash 3 can also effectively inhibit the metastasis and proliferation of tumor cells. These results demonstrate that 1&ndash 3 induce apoptosis in SGC-7901 cells through ROS-mediated mitochondrial damage and DNA damage pathways, as well as by inhibiting cell invasion, thereby exerting anti-tumor cell proliferation activity in vitro. |
| Databáze: | OpenAIRE |
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