人类癌细胞中的光诱导端粒DNA损伤。
Photo-induced telomeric DNA damage in human cancer cells.
作者信息
Weynand Justin, Episkopou Harikleia, Le Berre Gabriel, Gillard Martin, Dejeu Jérôme, Decottignies Anabelle, Defrancq Eric, Elias Benjamin
机构信息
Université catholique de Louvain (UCLouvain), Institut de la Matière Condensée et des Nanosciences (IMCN), Molecular Chemistry, Materials and Catalysis (MOST) Place Louis Pasteur 1, bte L4.01.02 B-1348 Louvain-la-Neuve Belgium
Université Grenoble-Alpes (UGA), Département de Chimie Moléculaire, UMR CNRS 5250, CS 40700 38058 Grenoble France
出版信息
RSC Chem Biol. 2022 Oct 31;3(12):1375-1379. doi: 10.1039/d2cb00192f. eCollection 2022 Nov 30.
Herein we report on the study of novel dinuclear ruthenium(ii) complexes designed to target and to photo-react with G-quadruplex telomeric DNA. Upon irradiation, complexes efficiently generate guanine radical cation sites as photo-oxidation products. The compounds also display efficient cell penetration with localization to the nucleus and show strong photocytotoxicity toward osteosarcoma cells. Thanks to a microscopic-based telomere dysfunction assay, which allows the direct visualization of DNA damage in cells, we brought the first evidence of forming photo-oxidative damage at telomeres . This emphasizes interesting prospects for the development of future cancer phototherapies.
在此，我们报告了对新型双核钌（II）配合物的研究，这些配合物旨在靶向端粒G-四链体DNA并与之发生光反应。经照射后，配合物能高效产生鸟嘌呤自由基阳离子位点作为光氧化产物。这些化合物还表现出高效的细胞穿透能力，并定位于细胞核，对骨肉瘤细胞显示出强烈的光细胞毒性。借助基于显微镜的端粒功能障碍检测方法，该方法可直接观察细胞中的DNA损伤，我们首次证明了在端粒处形成光氧化损伤。这突出了未来癌症光疗法发展的有趣前景。
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