The Potential Key Role of the NRF2/NQO1 Pathway in the Health Effects of Arsenic Pollution on SCC

Qianlei Yang, Rui Yan, Yuemei Mo, Haixuan Xia, Hanyi Deng, Xiaojuan Wang, Chunchun Li, Koichi Kato, Hengdong Zhang, Tingxu Jin, Jie Zhang and Yan An
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Qianlei Yang: Department of Toxicology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou 215123, China
Rui Yan: Department of Toxicology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou 215123, China
Yuemei Mo: Physical Examination Department, Center for Disease Control and Prevention of Suzhou Industrial Park, Suzhou 215100, China
Haixuan Xia: Department of Toxicology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou 215123, China
Hanyi Deng: Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China
Xiaojuan Wang: Department of Toxicology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou 215123, China
Chunchun Li: Changzhou Wujin District Center for Disease Control and Prevention, Changzhou 213164, China
Koichi Kato: Laboratory of Environmental Toxicology and Carcinogenesis, School of Pharmacy, Nihon University, Chiba 274-8555, Japan
Hengdong Zhang: Department of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210028, China
Tingxu Jin: Department of Toxicology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou 215123, China
Jie Zhang: Department of Toxicology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou 215123, China
Yan An: Department of Toxicology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou 215123, China

IJERPH, 2022, vol. 19, issue 13, 1-16

Abstract: Arsenic is widely present in nature and is a common environmental poison that seriously damages human health. Chronic exposure to arsenic is a major environmental poisoning factor that promotes cell proliferation and leads to malignant transformation. However, its molecular mechanism remains unclear. In this study, we found that arsenite can promote the transformation of immortalized human keratinocyte cells (HaCaT) from the G0/G1 phase to S phase and demonstrated malignant phenotypes. This phenomenon is accompanied by obviously elevated levels of NRF2, NQO1, Cyclin E, and Cyclin-dependent kinase 2 (CDK2). Silencing the NRF2 expression with small interfering RNA (siRNA) in arsenite-transformed (T-HaCaT) cells was shown to reverse the malignant phenotype. Furthermore, the siRNA silencing of NQO1 significantly decreased the levels of the cyclin E-CDK2 complex, inhibiting the G0/G1 to S phase cell cycle progression and transformation to the T-HaCaT phenotypes. Thus, we hypothesized that the NRF2/NQO1 pathway played a key role in the arsenite-induced malignancy of HaCaT cells. By increasing the expression of Cyclin E-CDK2, the NRF2/NQO1 pathway can affect cell cycle progression and cell proliferation. A new common health effect mechanism of arsenic carcinogenesis has been identified; thus, it would contribute to the development of novel treatments to prevent and treat skin cancer caused by arsenic.

Keywords: arsenite pollution; health effect; squamous cell carcinoma; NRF2/NQO1 pathway; cell proliferation; malignant transformation (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2022
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