An iridium (III) complex as potent anticancer agent induces apoptosis and autophagy in B16 cells through inhibition of the AKT/mTOR pathway

An iridium (III) complex as potent anticancer agent induces apoptosis and autophagy in... A new ligand THPDP (THPDP = 11-(6,7,8,9-tetrahydrophenazin-2-yl)dipyrido[3,2-a:2′,3′-c]phenazine) and its iridium(III) complex [Ir(ppy)2(THPDP)]PF6 (Ir-1) was synthesized and characterized by elemental analysis, IR, ESI-MS, 1H NMR and 13C NMR. The cytotoxicity in vitro of the complex against cancer cells B16, A549, Eca-109, SGC-7901, BEL-7402 and normal NIH 3T3 cell lines was evaluated using MTT method. The IC50 values of the complex toward B16, A549 and Eca-109 cells are 1.0 ± 0.02, 1.4 ± 0.03 and 1.6 ± 0.06 μM, respectively. The apoptosis was investigated with AO/EB and DAPI staining methods. The complex shows strong ability to inhibit the cell growth in B16, A549 and Eca-109 cells. Ir-1 can induce apoptosis, increase the intracellular ROS level, and cause a decrease in the mitochondrial membrane potential. The intracellular Ca2+ level and the release of cytochrome c were studied under a fluorescent microscope. The cell invasion and autophagy were also performed, and the cell cycle arrest was assayed by flow cytometry. The expression of Bcl-2 family proteins, PI3K, AKT, mTOR, P-mTOR was investigated by western blot. The results show that the complex induces apoptosis through ROS-mediated mitochondria dysfunction and inhibition of AKT/mTOR pathways. These findings are helpful for design and synthesis of iridium(III) complexes as potent anticancer drugs. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Medicinal Chemistry Elsevier

An iridium (III) complex as potent anticancer agent induces apoptosis and autophagy in B16 cells through inhibition of the AKT/mTOR pathway

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Publisher
Elsevier
Copyright
Copyright © 2017 Elsevier Masson SAS
ISSN
0223-5234
eISSN
1768-3254
D.O.I.
10.1016/j.ejmech.2017.12.087
Publisher site
See Article on Publisher Site

Abstract

A new ligand THPDP (THPDP = 11-(6,7,8,9-tetrahydrophenazin-2-yl)dipyrido[3,2-a:2′,3′-c]phenazine) and its iridium(III) complex [Ir(ppy)2(THPDP)]PF6 (Ir-1) was synthesized and characterized by elemental analysis, IR, ESI-MS, 1H NMR and 13C NMR. The cytotoxicity in vitro of the complex against cancer cells B16, A549, Eca-109, SGC-7901, BEL-7402 and normal NIH 3T3 cell lines was evaluated using MTT method. The IC50 values of the complex toward B16, A549 and Eca-109 cells are 1.0 ± 0.02, 1.4 ± 0.03 and 1.6 ± 0.06 μM, respectively. The apoptosis was investigated with AO/EB and DAPI staining methods. The complex shows strong ability to inhibit the cell growth in B16, A549 and Eca-109 cells. Ir-1 can induce apoptosis, increase the intracellular ROS level, and cause a decrease in the mitochondrial membrane potential. The intracellular Ca2+ level and the release of cytochrome c were studied under a fluorescent microscope. The cell invasion and autophagy were also performed, and the cell cycle arrest was assayed by flow cytometry. The expression of Bcl-2 family proteins, PI3K, AKT, mTOR, P-mTOR was investigated by western blot. The results show that the complex induces apoptosis through ROS-mediated mitochondria dysfunction and inhibition of AKT/mTOR pathways. These findings are helpful for design and synthesis of iridium(III) complexes as potent anticancer drugs.

Journal

European Journal of Medicinal ChemistryElsevier

Published: Feb 10, 2018

References

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