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Identification of two mitochondrial-targeting cyclometalated iridium(III) complexes as potent anti-glioma stem cells agents

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机构： [a]Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, China [b]The First Department of Neurosurgery, The Second Affiliated Hospital, Kunming Medical University, Kunming, 650101, China [c]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Kunming, 650223, China [d]Zoology Department, Faculty of Science, Minia University, Minia, 61519, Egypt [e]Kunming Medical University, Kunming, 650101, China [f]Laboratory of Animal Tumor Models, Department of Thoracic Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China

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关键词： Apoptosis Cancer stem cells Glioblastoma multiform Iridium(III) complexes Mitochondrial

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Glioma stem cells (GSCs) are thought to be responsible for the recurrence and invasion of glioblastoma multiform (GBM), which have been evaluated and exploited as the therapeutic target for GBM. Cyclometalated iridium(III) complexes have been demonstrated as the potential anticancer agents, however, their antitumor efficacies against GSCs are still unknown. Herein, we investigated the antitumor activity of two cyclometalated iridium(III) complexes [Ir(ppy)2L](PF6) (Ir1) and [Ir(thpy)2L](PF6) (Ir2) (ppy = 2-phenylpyridine, thpy = 2-(2-thienyl)pyridine and L = 4,4′-Bis(hydroxymethyl)-2,2′-bipyridine) against GSCs. The results clearly indicate that Ir1 and Ir2 kill GSCs selectively with IC50 values ranging from 5.26–9.05 μM. Further mechanism research display that Ir1 and Ir2 can suppress the proliferation of GSCs, penetrate into GSCs efficiently, localize to mitochondria, and induce mitochondria-mediated apoptosis, including the loss of mitochondrial membrane (MMP), elevation of intracellular reactive oxygen species (ROS) and caspases activation. Moreover, Ir1 and Ir2 can destroy the GSCs self-renewal and unlimited proliferation capacity by affecting the GSCs colony formation. According our knowledge, this is the first study to investigate the anti-GSCs properties of cyclometalated iridium(III) complexes. © 2019

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出版当年[2021]版：

大类 | 3 区生物

小类 | 2 区无机化学与核化学 3 区生化与分子生物学

最新[2023]版：

大类 | 2 区化学

小类 | 1 区无机化学与核化学 3 区生化与分子生物学

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第一作者机构： [a]Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, China

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