Anticancer activity and mechanism studies of photoactivated iridium(<scp>iii</scp>) complexes toward lung cancer A549 cells
Lin Zhou, Jiongbang Li, Ju Chen, Xin Yao, Xiandong Zeng, Yunjun Liu, Yi Wang, Xiuzhen Wang
Abstract
][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.