Issue 36, 2024

Anticancer activity and mechanism studies of photoactivated iridium(iii) complexes toward lung cancer A549 cells

Abstract

Cyclometalated iridium(III) compounds have been widely explored due to their outstanding photo-physical properties and multiple anticancer activities. In this paper, three cyclometalated iridium(III) compounds [Ir(ppy)2(DBDIP)]PF6 (5a), [Ir(bzq)2(DBDIP)]PF6 (5b), and [Ir(piq)2(DBDIP)]PF6 (5c) (ppy: 2-phenylpyridine; bzq: benzo[h]quinoline; piq: 1-phenylisoquinoline, and DBDIP: 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-imidazo[4,5-f][1,10]phenanthroline) were synthesized and the mechanism of antitumor activity was investigated. Compounds photoactivated by visible light show strong cytotoxicity against tumor cells, especially toward A549 cells. Biological experiments such as migration, cellular localization, mitochondrial membrane potential and permeability, reactive oxygen species (ROS) and calcium ion level detection were performed, and they demonstrated that the compounds induced the apoptosis of A549 cells through a mitochondrial pathway. At the same time, oxidative stress caused by ROS production increases the release of damage-related molecules and the expression of porogen gasdermin D (GSDMD), and the content of LDH released from damaged cell membranes also increased. Besides, the content of the lipid peroxidation product, malondialdehyde (MDA), increased and the expression of GPX4 decreased. These indicate that the compounds promote cell death by combining ferroptosis and pyroptosis. The results reveal that cyclometalated iridium(III) compounds 5a–5c may be a potential chemotherapeutic agent for photodynamic therapy of cancers.

Graphical abstract: Anticancer activity and mechanism studies of photoactivated iridium(iii) complexes toward lung cancer A549 cells

Supplementary files

Article information

Article type
Paper
Submitted
09 Jun 2024
Accepted
14 Aug 2024
First published
14 Aug 2024

Dalton Trans., 2024,53, 15176-15189

Anticancer activity and mechanism studies of photoactivated iridium(III) complexes toward lung cancer A549 cells

L. Zhou, J. Li, J. Chen, X. Yao, X. Zeng, Y. Liu, Y. Wang and X. Wang, Dalton Trans., 2024, 53, 15176 DOI: 10.1039/D4DT01677G

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