Network toxicology reveals collaborative mechanism of 4NQO and ethanol in esophageal squamous cell carcinogenesis
Tobacco smoking and alcohol consumption are significant risk factors for esophageal squamous cell carcinoma (ESCC), with their Collaborative interaction amplifying carcinogenic risks. To elucidate the role and underlying mechanisms of tobacco-alcohol co-exposure in ESCC pathogenesis, we treated the...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580825002742 |
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| author | Jianfeng Yuan Jianxin Guo Yu Wang Tiantian Xing Shuang Hou Chenchen Zhang Ming Huang Pengfei Zheng Ruifeng Li Zhongbing Wu Jing Li |
| author_facet | Jianfeng Yuan Jianxin Guo Yu Wang Tiantian Xing Shuang Hou Chenchen Zhang Ming Huang Pengfei Zheng Ruifeng Li Zhongbing Wu Jing Li |
| author_sort | Jianfeng Yuan |
| collection | DOAJ |
| description | Tobacco smoking and alcohol consumption are significant risk factors for esophageal squamous cell carcinoma (ESCC), with their Collaborative interaction amplifying carcinogenic risks. To elucidate the role and underlying mechanisms of tobacco-alcohol co-exposure in ESCC pathogenesis, we treated the immortalized human normal esophageal epithelial cell line NE-1 and C57BL/6 mice with 4-nitroquinoline-1-oxide (4NQO, a tobacco carcinogen analog) combined with ethanol. Results demonstrated that 4NQO-ethanol co-exposure accelerated esophageal squamous carcinogenesis. Through network toxicology and in vitro/in vivo experiments, we further validated that 4NQO-ethanol Combine exacerbated inflammatory responses and aggravated DNA damage. Mechanistically, 4NQO-ethanol co-exposure activated the TNF-α/TRAF2/NF-κB signaling pathway. Furthermore, the addition of the TNF-α inhibitor reduced the proliferative and invasive capacities of cells co-stimulated by 4NQO and ethanol. These findings indicate that tobacco-ethanol co-exposure promotes the development of esophageal squamous cell carcinoma by inducing inflammation and DNA damage through TNF-α/TRAF2/NF-κB signaling. |
| format | Article |
| id | doaj-art-9c2e6dfddf5f4fd9b7c10b6a9d82c42f |
| institution | Matheson Library |
| issn | 2405-5808 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj-art-9c2e6dfddf5f4fd9b7c10b6a9d82c42f2025-08-03T04:42:53ZengElsevierBiochemistry and Biophysics Reports2405-58082025-09-0143102187Network toxicology reveals collaborative mechanism of 4NQO and ethanol in esophageal squamous cell carcinogenesisJianfeng Yuan0Jianxin Guo1Yu Wang2Tiantian Xing3Shuang Hou4Chenchen Zhang5Ming Huang6Pengfei Zheng7Ruifeng Li8Zhongbing Wu9Jing Li10College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang, 050017, ChinaCollege of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang, 050017, ChinaCollege of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang, 050017, ChinaCollege of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang, 050017, ChinaCollege of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang, 050017, ChinaCollege of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang, 050017, ChinaCollege of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang, 050017, ChinaCollege of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang, 050017, ChinaCollege of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang, 050017, ChinaCollege of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang, 050017, China; Corresponding author.College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang, 050017, China; Department of Traditional Chinese Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China; Corresponding author. College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang, 050017, China.Tobacco smoking and alcohol consumption are significant risk factors for esophageal squamous cell carcinoma (ESCC), with their Collaborative interaction amplifying carcinogenic risks. To elucidate the role and underlying mechanisms of tobacco-alcohol co-exposure in ESCC pathogenesis, we treated the immortalized human normal esophageal epithelial cell line NE-1 and C57BL/6 mice with 4-nitroquinoline-1-oxide (4NQO, a tobacco carcinogen analog) combined with ethanol. Results demonstrated that 4NQO-ethanol co-exposure accelerated esophageal squamous carcinogenesis. Through network toxicology and in vitro/in vivo experiments, we further validated that 4NQO-ethanol Combine exacerbated inflammatory responses and aggravated DNA damage. Mechanistically, 4NQO-ethanol co-exposure activated the TNF-α/TRAF2/NF-κB signaling pathway. Furthermore, the addition of the TNF-α inhibitor reduced the proliferative and invasive capacities of cells co-stimulated by 4NQO and ethanol. These findings indicate that tobacco-ethanol co-exposure promotes the development of esophageal squamous cell carcinoma by inducing inflammation and DNA damage through TNF-α/TRAF2/NF-κB signaling.http://www.sciencedirect.com/science/article/pii/S2405580825002742Esophageal squamous cell carcinomaTobacco smoking4-Nitroquinoline-1-oxideEthanolTNF-α/TRAF2/NF-κB signaling pathway |
| spellingShingle | Jianfeng Yuan Jianxin Guo Yu Wang Tiantian Xing Shuang Hou Chenchen Zhang Ming Huang Pengfei Zheng Ruifeng Li Zhongbing Wu Jing Li Network toxicology reveals collaborative mechanism of 4NQO and ethanol in esophageal squamous cell carcinogenesis Biochemistry and Biophysics Reports Esophageal squamous cell carcinoma Tobacco smoking 4-Nitroquinoline-1-oxide Ethanol TNF-α/TRAF2/NF-κB signaling pathway |
| title | Network toxicology reveals collaborative mechanism of 4NQO and ethanol in esophageal squamous cell carcinogenesis |
| title_full | Network toxicology reveals collaborative mechanism of 4NQO and ethanol in esophageal squamous cell carcinogenesis |
| title_fullStr | Network toxicology reveals collaborative mechanism of 4NQO and ethanol in esophageal squamous cell carcinogenesis |
| title_full_unstemmed | Network toxicology reveals collaborative mechanism of 4NQO and ethanol in esophageal squamous cell carcinogenesis |
| title_short | Network toxicology reveals collaborative mechanism of 4NQO and ethanol in esophageal squamous cell carcinogenesis |
| title_sort | network toxicology reveals collaborative mechanism of 4nqo and ethanol in esophageal squamous cell carcinogenesis |
| topic | Esophageal squamous cell carcinoma Tobacco smoking 4-Nitroquinoline-1-oxide Ethanol TNF-α/TRAF2/NF-κB signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S2405580825002742 |
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