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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2025; 31(32): 108654
Published online Aug 28, 2025. doi: 10.3748/wjg.v31.i32.108654
Published online Aug 28, 2025. doi: 10.3748/wjg.v31.i32.108654
Melatonin-induced ferroptosis in pancreatic cancer cells by stimulating endoplasmic reticulum stress and inhibiting alanine-serine-cysteine transporter 2-driven glutamine metabolism
Qian Zhao, Huang-Min Wu, Qun-Ying Yang, Hong Zhao, Xiang-Yin Lv, Department of Gastroenterology, Dongyang People’s Hospital, Dongyang 322100, Zhejiang Province, China
Hui Zhang, Department of Gastroenterology, Weishan Branch of Dongyang People’s Hospital, Dongyang 322100, Zhejiang Province, China
Le Kang, Department of Scientific Research, Dongyang People’s Hospital, Dongyang 322100, Zhejiang Province, China
Co-first authors: Qian Zhao and Hui Zhang.
Author contributions: Lv XY and Zhao Q conceptualized the study; Zhao Q and Zhang H contributed equally as co-first authors; Zhao Q and Wu HM conducted the experiments; Zhao Q and Yang QY handled data collection; Lv XY and Kang L carried out the data analysis; Zhao Q and Zhao H drafted the initial manuscript; Lv XY and Wu HM reviewed and refined the final version of the manuscript; all authors approved the final version of the article.
Supported by Jinhua Municipal Science and Technology Bureau, No. 2022-4-254.
Institutional review board statement: This study does not involve any animal or human experiment, therefore it does not require approval from an ethics committee.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets and materials utilized in this research are available from the corresponding author upon request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiang-Yin Lv, Professor, Department of Gastroenterology, Dongyang People’s Hospital, No. 60 Wuning West Road, Dongyang 322100, Zhejiang Province, China. lvxiangyin1982@163.com
Received: June 10, 2025
Revised: July 10, 2025
Accepted: August 4, 2025
Published online: August 28, 2025
Processing time: 77 Days and 19.9 Hours
Revised: July 10, 2025
Accepted: August 4, 2025
Published online: August 28, 2025
Processing time: 77 Days and 19.9 Hours
Core Tip
Core Tip: In the present study, we demonstrate that melatonin activates endoplasmic reticulum stress-mediated-ferroptosis in the protein kinase R-like endoplasmic reticulum kinase-eukaryotic initiation factor 2α-activating transcription factor 4 axis via inhibition of the alanine-serine-cysteine transporter 2-glutathione peroxidase 4 signaling pathway, thereby exerting an anti-cancer effect on pancreatic cancer cells. These new findings suggest that melatonin may act as a potent anti-tumor agent and may have great potential as an adjuvant therapy in the future.