光活化铱(III)配合物对肺癌A549细胞的抗癌活性及机制研究。
Anticancer activity and mechanism studies of photoactivated iridium(III) complexes toward lung cancer A549 cells.
发表日期:2024 Sep 02
作者:
Lin Zhou, Jiongbang Li, Ju Chen, Xin Yao, Xiandong Zeng, Yunjun Liu, Yi Wang, Xiuzhen Wang
来源:
Cell Death & Disease
摘要:
环金属化铱(III)化合物因其出色的光物理特性和多种抗癌活性而被广泛研究。本文研究了三种环金属铱(III)化合物[Ir(ppy)2(DBDIP)]PF6 (5a)、[Ir(bzq)2(DBDIP)]PF6 (5b)和[Ir(piq)2(DBDIP) )]PF6 (5c) (ppy:2-苯基吡啶;bzq:苯并[h]喹啉;piq:1-苯基异喹啉;DBDIP:2-(2,3-二氢苯并[b][1,4]二恶英-6-合成了(yl)-1H-咪唑并[4,5-f][1,10]菲咯啉)并研究了其抗肿瘤活性机制。可见光光激活的化合物对肿瘤细胞,尤其是 A549 细胞表现出强烈的细胞毒性。进行了迁移、细胞定位、线粒体膜电位和通透性、活性氧(ROS)和钙离子水平检测等生物学实验,证明这些化合物通过线粒体途径诱导A549细胞凋亡。同时,ROS产生引起的氧化应激增加了损伤相关分子的释放和致孔剂gasdermin D(GSDMD)的表达,受损细胞膜释放的LDH含量也增加。此外,脂质过氧化产物丙二醛(MDA)含量增加,GPX4表达减少。这些表明这些化合物通过结合铁死亡和细胞焦亡来促进细胞死亡。结果表明,环金属化铱(III)化合物5a-5c可能是癌症光动力疗法的潜在化疗剂。
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.