School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
J Inorg Biochem. 2021 Aug;221:111465. doi: 10.1016/j.jinorgbio.2021.111465. Epub 2021 May 11.
Iridium(III) complexes have the potential to serve as novel therapeutic drugs for treating tumor. In this work, three new complexes Ir(ppy)(cdppz) (1) (ppy = 2-phenylpyridine, cdppz = 11-chlorodipyrido[3,2-a,2',3'-c]phenazine), Ir(bzq)(cdppz) (2) (bzq = benzo[h]quinolone) and Ir(piq)(cdppz) (3) (piq = 1-phenylisoquinoline) were prepared as well as characterized. MTT (3-(4,5-dimethylthiazole)-2,5-diphenyltetraazolium bromide) assay revealed that the complex 2 exerted potent cytotoxicity against to various cancer cells lines and particularly for SGC-7901 cells. Meanwhile, the complexes could suppress cell colonies formation and migration ability. Apoptosis assays of AO/EB staining as well as flow cytometry revealed that the synthesized complexes may cause apoptosis of SGC-7901 cells. Moreover, the decline of mitochondrial membrane potential (MMP), elevation of intracellular reactive oxygen species (ROS) levels and release of cytochrome c demonstrated the complexes could cause apoptosis mainly through the mitochondrial death pathway and arrest cell at G0/G1 phase. Additionally, the complexes have significant influence on the expression of proteins which is interrelated to cell apoptosis. In summary, our studies provided fundamental information regarding the further study of the possible anticancer mechanisms of iridium (III) complexes.
铱（III）配合物有可能成为治疗肿瘤的新型治疗药物。在这项工作中，我们制备了三种新的配合物Ir(ppy)(cdppz) (1) (ppy = 2-苯基吡啶，cdppz = 11-氯二吡啶并[3,2-a,2',3'-c]吩嗪)、Ir(bzq)(cdppz) (2) (bzq = 苯并喹啉)和Ir(piq)(cdppz) (3) (piq = 1-苯基异喹啉)，并对它们进行了表征。MTT（3-(4,5-二甲基噻唑)-2,5-二苯基四氮唑溴盐）试验表明，配合物 2 对多种癌细胞系表现出很强的细胞毒性，特别是对 SGC-7901 细胞。同时，这些配合物能够抑制细胞集落形成和迁移能力。AO/EB 染色和流式细胞术的凋亡试验表明，合成的配合物可能导致 SGC-7901 细胞凋亡。此外，线粒体膜电位（MMP）下降、细胞内活性氧（ROS）水平升高和细胞色素 c 的释放表明，这些配合物主要通过线粒体死亡途径引起细胞凋亡，并使细胞停滞在 G0/G1 期。此外，这些配合物对与细胞凋亡相关的蛋白质的表达有显著影响。总之，我们的研究为进一步研究铱（III）配合物的可能抗癌机制提供了基础信息。
