Au-24 as a potential thioredoxin reductase inhibitor in hepatocellular carcinoma cells
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 oxidativ...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-03-01
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| Series: | Pharmacological Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661822000585 |
| _version_ | 1827391176778448896 |
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| author | Gaopan Dong Xiaohan Ye Shumei Wang Wenhua Li Rong Cai Lupei Du Xiaodong Shi Minyong Li |
| author_facet | Gaopan Dong Xiaohan Ye Shumei Wang Wenhua Li Rong Cai Lupei Du Xiaodong Shi Minyong Li |
| author_sort | Gaopan Dong |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T17:06:56Z |
| format | Article |
| id | doaj.art-756667a2c2814f878cc622f4f2b1ee00 |
| institution | Directory Open Access Journal |
| issn | 1096-1186 |
| language | English |
| last_indexed | 2024-03-08T17:06:56Z |
| publishDate | 2022-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj.art-756667a2c2814f878cc622f4f2b1ee002024-01-04T04:36:25ZengElsevierPharmacological Research1096-11862022-03-01177106113Au-24 as a potential thioredoxin reductase inhibitor in hepatocellular carcinoma cellsGaopan Dong0Xiaohan Ye1Shumei Wang2Wenhua Li3Rong Cai4Lupei Du5Xiaodong Shi6Minyong Li7Key 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, ChinaKey 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, USAKey Laboratory of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, ChinaKey Laboratory of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, ChinaKey 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, USAKey Laboratory of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, ChinaDepartment of Chemistry, University of South Florida, Tampa, FL 33647, USA; Corresponding authors.Key Laboratory of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S1043661822000585Thioredoxin reductase (TrxR) inhibitorSignaling pathwaysApoptosisHepatocellular carcinoma (HCC) |
| spellingShingle | Gaopan Dong Xiaohan Ye Shumei Wang Wenhua Li Rong Cai Lupei Du Xiaodong Shi Minyong Li Au-24 as a potential thioredoxin reductase inhibitor in hepatocellular carcinoma cells Pharmacological Research Thioredoxin reductase (TrxR) inhibitor Signaling pathways Apoptosis Hepatocellular carcinoma (HCC) |
| title | Au-24 as a potential thioredoxin reductase inhibitor in hepatocellular carcinoma cells |
| title_full | Au-24 as a potential thioredoxin reductase inhibitor in hepatocellular carcinoma cells |
| title_fullStr | Au-24 as a potential thioredoxin reductase inhibitor in hepatocellular carcinoma cells |
| title_full_unstemmed | Au-24 as a potential thioredoxin reductase inhibitor in hepatocellular carcinoma cells |
| title_short | Au-24 as a potential thioredoxin reductase inhibitor in hepatocellular carcinoma cells |
| title_sort | au 24 as a potential thioredoxin reductase inhibitor in hepatocellular carcinoma cells |
| topic | Thioredoxin reductase (TrxR) inhibitor Signaling pathways Apoptosis Hepatocellular carcinoma (HCC) |
| url | http://www.sciencedirect.com/science/article/pii/S1043661822000585 |
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