Design, Synthesis, and Anticancer Effect Studies of Iridium(III) Polypyridyl Complexes against SGC-7901 Cells
oleh: Li-Xia Zhang, Yi-Ying Gu, Yang-Jie Wang, Lan Bai, Fan Du, Wen-Yao Zhang, Miao He, Yun-Jun Liu, Yan-Zhong Chen
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2019-08-01 |
Deskripsi
Three iridium(III) complexes ([Ir(Hppy)<sub>2</sub>(L)](PF<sub>6</sub>) (Hppy = 2-phenylpyridine, L = 5-nitrophenanthroline, NP), <b>1</b>; 5-nitro-6-amino-phenanthroline (NAP), <b>2</b>; and 5,6-diamino-phenanthroline (DAP) <b>3</b> were synthesized and characterized. The cytotoxicities of Ir(III) complexes <b>1</b>−<b>3</b> 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 IC<sub>50</sub> values of 3.6 ± 0.1 µM for <b>1</b>, 14.1 ± 0.5 µM for <b>2</b>, and 11.1 ± 1.3 µM for <b>3</b>. Further studies showed that <b>1</b>−<b>3</b> induce cell apoptosis/death through DNA damage, cell cycle arrest at the S or G0/G1 phase, ROS elevation, increased levels of Ca<sup>2+</sup>, high mitochondrial membrane depolarization, and cellular ATP depletion. Transwell and Colony-Forming assays revealed that complexes <b>1</b>−<b>3</b> can also effectively inhibit the metastasis and proliferation of tumor cells. These results demonstrate that <b>1</b>−<b>3</b> 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.