Long-Term Treatment with Low-Level Arsenite Induces Aberrant Proliferation and Migration via Redox Rebalance in Human Urothelial Cells
Chronic exposure to arsenic via drinking water can induce bladder cancer in humans. Nevertheless, there is little knowledge about the precise mechanisms of this. Abnormal elevations in cell proliferation and migration have repeatedly been identified as the first cellular traits of carcinogenesis. Th...
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2025-06-01
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| author | Xiangli Yan Qing Zhou Shuhua Xi Peiyu Jin |
| author_facet | Xiangli Yan Qing Zhou Shuhua Xi Peiyu Jin |
| author_sort | Xiangli Yan |
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| description | Chronic exposure to arsenic via drinking water can induce bladder cancer in humans. Nevertheless, there is little knowledge about the precise mechanisms of this. Abnormal elevations in cell proliferation and migration have repeatedly been identified as the first cellular traits of carcinogenesis. The aims of this study are to uncover the molecular mechanisms underlying arsenic-induced aberrant proliferation and migration of uroepithelium cells by exploring the role of cellular redox modulation. Our results show significant elevations in the levels of ROS and GSH, Trx1, components of the Nrf2 system, and NLRP3 inflammasome activity in the cells chronically treated with arsenite, which also experienced markedly enhanced proliferation and migration capacities. Additionally, ROS inhibitors, NLRP3, and the above antioxidant system could suppress this enhancement of the proliferation and migration capacities and reverse overexpression in these cells. However, only the AKT and ERK inhibitors were capable of reversing EGF, TGFα, and HSP90 overexpression. In conclusion, our findings indicate that the cellular redox status in the uroepithelium following chronic treatment with low-level arsenite was rebalanced due to ROS overproduction and compensatory upregulation of the redox control systems, which may allow ROS and Trx1 to be maintained at higher levels to facilitate cell proliferation and migration via overstimulation of the related signaling pathways. |
| format | Article |
| id | doaj-art-711681fc78474272b078472e8aaf22e7 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-06-01 |
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| series | Cells |
| spelling | doaj-art-711681fc78474272b078472e8aaf22e72025-08-20T03:26:20ZengMDPI AGCells2073-44092025-06-01141291210.3390/cells14120912Long-Term Treatment with Low-Level Arsenite Induces Aberrant Proliferation and Migration via Redox Rebalance in Human Urothelial CellsXiangli Yan0Qing Zhou1Shuhua Xi2Peiyu Jin3Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, No 77 Puhe Road, Shenyang North New Area, Shenyang 110122, ChinaDepartment of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang 110122, ChinaDepartment of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang 110122, ChinaDepartment of Nutrition and Food Hygiene, School of Public Health, China Medical University, No 77 Puhe Road, Shenyang North New Area, Shenyang 110122, ChinaChronic exposure to arsenic via drinking water can induce bladder cancer in humans. Nevertheless, there is little knowledge about the precise mechanisms of this. Abnormal elevations in cell proliferation and migration have repeatedly been identified as the first cellular traits of carcinogenesis. The aims of this study are to uncover the molecular mechanisms underlying arsenic-induced aberrant proliferation and migration of uroepithelium cells by exploring the role of cellular redox modulation. Our results show significant elevations in the levels of ROS and GSH, Trx1, components of the Nrf2 system, and NLRP3 inflammasome activity in the cells chronically treated with arsenite, which also experienced markedly enhanced proliferation and migration capacities. Additionally, ROS inhibitors, NLRP3, and the above antioxidant system could suppress this enhancement of the proliferation and migration capacities and reverse overexpression in these cells. However, only the AKT and ERK inhibitors were capable of reversing EGF, TGFα, and HSP90 overexpression. In conclusion, our findings indicate that the cellular redox status in the uroepithelium following chronic treatment with low-level arsenite was rebalanced due to ROS overproduction and compensatory upregulation of the redox control systems, which may allow ROS and Trx1 to be maintained at higher levels to facilitate cell proliferation and migration via overstimulation of the related signaling pathways.https://www.mdpi.com/2073-4409/14/12/912arseniteurothelial cellsredox balancethioredoxin systemglutathione system |
| spellingShingle | Xiangli Yan Qing Zhou Shuhua Xi Peiyu Jin Long-Term Treatment with Low-Level Arsenite Induces Aberrant Proliferation and Migration via Redox Rebalance in Human Urothelial Cells Cells arsenite urothelial cells redox balance thioredoxin system glutathione system |
| title | Long-Term Treatment with Low-Level Arsenite Induces Aberrant Proliferation and Migration via Redox Rebalance in Human Urothelial Cells |
| title_full | Long-Term Treatment with Low-Level Arsenite Induces Aberrant Proliferation and Migration via Redox Rebalance in Human Urothelial Cells |
| title_fullStr | Long-Term Treatment with Low-Level Arsenite Induces Aberrant Proliferation and Migration via Redox Rebalance in Human Urothelial Cells |
| title_full_unstemmed | Long-Term Treatment with Low-Level Arsenite Induces Aberrant Proliferation and Migration via Redox Rebalance in Human Urothelial Cells |
| title_short | Long-Term Treatment with Low-Level Arsenite Induces Aberrant Proliferation and Migration via Redox Rebalance in Human Urothelial Cells |
| title_sort | long term treatment with low level arsenite induces aberrant proliferation and migration via redox rebalance in human urothelial cells |
| topic | arsenite urothelial cells redox balance thioredoxin system glutathione system |
| url | https://www.mdpi.com/2073-4409/14/12/912 |
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