4.6 Article

Evaluation of anticancer effects in vitro of new iridium(III) complexes targeting the mitochondria

Journal

JOURNAL OF INORGANIC BIOCHEMISTRY
Volume 221, Issue -, Pages -

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2021.111465

Keywords

Iridium(III) complexes; Cytotoxicity; Apoptosis; ROS; Mitochondria

Funding

  1. National Nature Science Foundation of China [21877018]
  2. Guangzhou Science and Technology Program Key Projects [201904010402]

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The synthesized iridium(III) complexes exhibited potent cytotoxicity against various cancer cell lines, inhibited cell colony formation and migration, and induced apoptosis through the mitochondrial death pathway.
Iridium(III) complexes have the potential to serve as novel therapeutic drugs for treating tumor. In this work, three new complexes [Ir(ppy)2(cdppz)](PF6) (1) (ppy = 2-phenylpyridine, cdppz = 11-chlorodipyrido[3,2a,2 ',3 '-c]phenazine), [Ir(bzq)2(cdppz)](PF6) (2) (bzq = benzo[h]quinolone) and [Ir(piq)2(cdppz)](PF6) (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.

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