ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1559675
This article is part of the Research TopicExploring Novel Metal-Based Compounds for Enhanced Therapeutic Efficacy and SafetyView all 4 articles
Anticancer Effects of Zinc Ion-Mediated DNA Demethylation in Oesophageal Squamous Cell Carcinoma
Provisionally accepted
- 1The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
- 2Zhejiang Cancer Hospital, University of Chinese Academy of Sciences, Hangzhou, China
- 3Wenzhou Medical University, Wenzhou, Zhejiang Province, China
- 4Taixing People's Hospital, Taixing, China
- 5LC-Bio Technologies, hangzhou, China
- 6Jiangxi Cancer Hospital, Nanchang, Jiangxi Province, China
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Abnormalities in trace elements and the incidence of oesophageal squamous cell carcinoma (ESCC) have been reported in China. Zinc ions (Zn²⁺) are known to regulate DNA methylation by stabilizing methylase activity. However, the relationship between DNA methylation and Zn²⁺ dysregulation in ESCC cells remains unclear. In this study, we examined changes in the biological behavior of ESCC cells treated with or without Zn²⁺ Methods Biological behaviour changes in ESCC cells treated with or without Zn 2+ were analysed. Differences in the methylome and transcriptome of Zn 2+ -treated cells were determined by reduced representation bisulfite sequencing and RNA sequencing. An MTT cell viability assay was used to evaluate the cytotoxicity of cisplatin combined with Zn 2+ .Zn 2+ can inhibit the malignant biological behaviour of ESCC cells. CpG methylation levels of promoter regions were decreased after Zn 2+ treatment in both ESCC and control cells. The degree of DNA methylation of genes encoding the metal ion-binding factors MT1E, MT1H and MT1X was significantly decreased, but their RNA expression levels were significantly increased after Zn 2+ treatment. Zn 2+ may enhance the expression of metallothioneins (MTs) via positive feedback through methylation regulation mechanisms. In vitro assays showed that the IC50 of Zn 2+ in ESCC cells was significantly lower than that in cells treated with cisplatin alone. In addition, ECa patients with high MT1E expression had a better prognosis.Zn 2+ can reduce the methylation level and malignant biological behaviour of ESCC cells. The combination of Zn 2+ and cisplatin increases ESCC inhibition. Further study of MTs as biomarkers and targets in ESCC is warranted.
Keywords: Oesophageal squamous cell carcinoma, Zinc ions, DNA Methylation, Gene Expression, Metallothioneins (MTs), combined treatment, biomarkers
Received: 13 Jan 2025; Accepted: 30 Apr 2025.
Copyright: © 2025 Zhou, Wang, Huang, Yang, Ye, Shen, Lv, Mao and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: An Zhao, Zhejiang Cancer Hospital, University of Chinese Academy of Sciences, Hangzhou, China
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