Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 183, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2019.111721
Keywords
Rhodium(I) NHC complexs; Thioredoxin reductase; Apoptosis; Reactive oxygen species; Hepatocellular carcinoma
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Funding
- National Natural Science Foundation of China [81703337]
- Jiangsu Specially-Appointed Professors program
- Open Project of State Key Laboratory of Natural Medicines [SKLNMKF201808, SKLNMKF201712]
- State Key Laboratory of Coordination Chemistry, Nanjing University
- Six Talent Peaks Project in Jiangsu Province of China [SWYY-069]
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Thioredoxin reductase (TrxR) is often overexpressed in different types of cancer cells including hepatocellular carcinoma (HCC) cells and regarded as a target with great promise for anticancer drug research and development. Here, we have synthesized and characterized nine new designed rhodium(I) N-heterocyclic carbene (NHC) complexes. All of them were effective towards cancer cells, especially complex le was more active than cisplatin and manifested strong antiproliferative activity against HCC cells. In vivo anticancer studies showed that le significantly repressed tumor growth in an HCC nude mouse model and ameliorated liver lesions in a chronic HCC model caused by CCl4. Notably, a mechanistic study revealed that le can strongly inhibit TrxR system both in vitro and in vivo. Furthermore, le promoted intracellular ROS accumulation, damaged mitochondrial membrane potential, promoted cancer cell apoptosis and blocked the cells in the Cl phase. (C) 2019 Elsevier Masson SAS. All rights reserved.
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