1. A Gold(I) Complex Containing an Oleanolic Acid Derivative as a Potential Anti-Ovarian-Cancer Agent by Inhibiting TrxR and Activating ROS-Mediated ERS.
- Author
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Bian M, Sun Y, Liu Y, Xu Z, Fan R, Liu Z, and Liu W
- Subjects
- Antineoplastic Agents chemistry, Cell Cycle Checkpoints drug effects, Cell Line, Tumor, Coordination Complexes chemistry, Endoplasmic Reticulum Stress, Female, Gold pharmacology, Humans, Oxidation-Reduction, Thioredoxin-Disulfide Reductase chemistry, Antineoplastic Agents pharmacology, Antioxidants pharmacology, Apoptosis drug effects, Cell Survival drug effects, Coordination Complexes pharmacology, Gold chemistry, Oleanolic Acid chemistry, Ovarian Neoplasms drug therapy, Reactive Oxygen Species metabolism, Thioredoxin-Disulfide Reductase antagonists & inhibitors
- Abstract
Many cancer cells critically rely on antioxidant systems for cell survival and are vulnerable to further oxidative impairment triggered by agents generating reactive oxygen species (ROS). Therefore, the classical design and development of inhibitors that target antioxidant defense enzymes such as thioredoxin reductase (TrxR) can be a promising anticancer strategy. Herein, it is shown that a gold(I) complex containing an oleanolic acid derivative (4 b) induces apoptosis of ovarian cancer A2780 cells by activating endoplasmic reticulum stress (ERS). It can inhibit TrxR enzyme activity to elevate ROS, mediate ERS and mitochondrial dysfunction, and finally leads to cell cycle arrest and apoptosis of A2780 cells. Notably, this complex inhibits A2780 xenograft tumor growth accompanied by increased ERS level and decreased TrxR activity in tumor tissues., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2020
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