Highly Charged, Cytotoxic, Cyclometalated Iridium(III) Complexes as Cancer Stem Cell Mitochondriotropics

Kristine Laws; Arvin Eskandari; Chunxin Lu; Kogularamanan Suntharalingam

doi:10.1002/chem.201803521

Highly Charged, Cytotoxic, Cyclometalated Iridium(III) Complexes as Cancer Stem Cell Mitochondriotropics

Kristine Laws, Arvin Eskandari, Chunxin Lu, Kogularamanan Suntharalingam^*

^*Corresponding author for this work

Jiaxing University

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

Abstract

The cancer stem cell (CSC) toxicity and mechanism of action of a series of iridium(III) complexes bearing polypridyl and charged 1-methyl-2-(2-pyridyl)pyridinium ligands, 1–4 is reported. The most effective complex (containing 1,10-phenanthroline), 3, kills CSCs and bulk cancer cells with equal potency (in the micromolar range), indicating that it could potentially remove heterogenous tumour populations with a single dose. Encouragingly, 3 also inhibits mammopshere formation to a similar extent as salinomycin, a well-established anti-CSC agent. This complex induces CSC apoptosis by mitochondrial membrane depolarization, inhibition of mitochondrial metabolism, and intracellular reactive oxygen species (ROS) generation. To the best of our knowledge, this is the first study to investigate the anti-CSC properties of iridium complexes.

Original language	English
Pages (from-to)	15205-15210
Journal	Chemistry - A European Journal
Volume	24
Issue number	57
Early online date	27 Jul 2018
DOIs	https://doi.org/10.1002/chem.201803521
Publication status	Published - 12 Oct 2018

Keywords

bioinorganic chemistry
cancer
cyclometallation
iridium
mitochondria

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10.1002/chem.201803521

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title = "Highly Charged, Cytotoxic, Cyclometalated Iridium(III) Complexes as Cancer Stem Cell Mitochondriotropics",

abstract = "The cancer stem cell (CSC) toxicity and mechanism of action of a series of iridium(III) complexes bearing polypridyl and charged 1-methyl-2-(2-pyridyl)pyridinium ligands, 1–4 is reported. The most effective complex (containing 1,10-phenanthroline), 3, kills CSCs and bulk cancer cells with equal potency (in the micromolar range), indicating that it could potentially remove heterogenous tumour populations with a single dose. Encouragingly, 3 also inhibits mammopshere formation to a similar extent as salinomycin, a well-established anti-CSC agent. This complex induces CSC apoptosis by mitochondrial membrane depolarization, inhibition of mitochondrial metabolism, and intracellular reactive oxygen species (ROS) generation. To the best of our knowledge, this is the first study to investigate the anti-CSC properties of iridium complexes.",

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AU - Laws, Kristine

AU - Eskandari, Arvin

AU - Lu, Chunxin

AU - Suntharalingam, Kogularamanan

PY - 2018/10/12

Y1 - 2018/10/12

N2 - The cancer stem cell (CSC) toxicity and mechanism of action of a series of iridium(III) complexes bearing polypridyl and charged 1-methyl-2-(2-pyridyl)pyridinium ligands, 1–4 is reported. The most effective complex (containing 1,10-phenanthroline), 3, kills CSCs and bulk cancer cells with equal potency (in the micromolar range), indicating that it could potentially remove heterogenous tumour populations with a single dose. Encouragingly, 3 also inhibits mammopshere formation to a similar extent as salinomycin, a well-established anti-CSC agent. This complex induces CSC apoptosis by mitochondrial membrane depolarization, inhibition of mitochondrial metabolism, and intracellular reactive oxygen species (ROS) generation. To the best of our knowledge, this is the first study to investigate the anti-CSC properties of iridium complexes.

AB - The cancer stem cell (CSC) toxicity and mechanism of action of a series of iridium(III) complexes bearing polypridyl and charged 1-methyl-2-(2-pyridyl)pyridinium ligands, 1–4 is reported. The most effective complex (containing 1,10-phenanthroline), 3, kills CSCs and bulk cancer cells with equal potency (in the micromolar range), indicating that it could potentially remove heterogenous tumour populations with a single dose. Encouragingly, 3 also inhibits mammopshere formation to a similar extent as salinomycin, a well-established anti-CSC agent. This complex induces CSC apoptosis by mitochondrial membrane depolarization, inhibition of mitochondrial metabolism, and intracellular reactive oxygen species (ROS) generation. To the best of our knowledge, this is the first study to investigate the anti-CSC properties of iridium complexes.

KW - bioinorganic chemistry

KW - cancer

KW - cyclometallation

KW - iridium

KW - mitochondria

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Highly Charged, Cytotoxic, Cyclometalated Iridium(III) Complexes as Cancer Stem Cell Mitochondriotropics

Abstract

Keywords

UN SDGs

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