Au-24 as a potential thioredoxin reductase inhibitor in hepatocellular carcinoma cells

Gaopan Dong; Xiaohan Ye; Shumei Wang; Wenhua Li; Rong Cai; Lupei Du; Xiaodong Shi; Minyong Li

Pharmacological Research (Mar 2022)

Au-24 as a potential thioredoxin reductase inhibitor in hepatocellular carcinoma cells

Gaopan Dong,
Xiaohan Ye,
Shumei Wang,
Wenhua Li,
Rong Cai,
Lupei Du,
Xiaodong Shi,
Minyong Li

Affiliations

Gaopan Dong: Key Laboratory of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China; School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, China
Xiaohan Ye: Key Laboratory of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China; Department of Chemistry, University of South Florida, Tampa, FL 33647, USA
Shumei Wang: Key Laboratory of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
Wenhua Li: Key Laboratory of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
Rong Cai: Key Laboratory of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China; Department of Chemistry, University of South Florida, Tampa, FL 33647, USA
Lupei Du: Key Laboratory of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
Xiaodong Shi: Department of Chemistry, University of South Florida, Tampa, FL 33647, USA; Corresponding authors.
Minyong Li: Key Laboratory of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China; Corresponding authors.

Journal volume & issue: Vol. 177
p. 106113

Abstract

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A novel TrxR inhibitor Au-24 and its inhibitory ability to hepatocellular carcinoma in vitro and in vivo is reported herein. Au-24 can suppress HepG2 cells from proliferating by lowering mitochondrial membrane potential (MMP) and increasing reactive oxygen species (ROS) levels, resulting in oxidative stress, which causes DNA damage, autophagy, cell cycle arrest, and apoptosis. This compound can also affect the normal function of apoptosis, MAPK, PI3K/AKT/mTOR, NF-κB, STAT3 signaling pathways. In vivo experiments revealed that Au-24 inhibited HepG2 tumor growth more effectively than AA1 (chloro(triethylphosphine)gold(I)) by decreasing Ki67 and CD31 protein expression and promoting tumor cell apoptosis and necrosis lesions. As a result, Au-24 was found to be a promising candidate as a TrxR inhibitor for the treatment of hepatocellular carcinoma (HCC) in both in vivo and in vitro experiments.

Published in Pharmacological Research

ISSN: 1096-1186 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.sciencedirect.com/journal/pharmacological-research

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