ORIGINAL RESEARCH article
Front. Oncol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1642866
This article is part of the Research TopicDiscovery of Small Molecule Lead Compounds: a Driving Force to Unravel New Anti-Cancer Targets and Mechanisms - Volume IIIView all 4 articles
Effects of parthenolide on amino acid metabolism and oxidative stress in lung adenocarcinoma based on quantitative proteomic analysis, targeted amino acid metabolomics, network pharmacology, and experimental validation
Provisionally accepted
- Jinzhou Medical University, Jinzhou, China
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Background: Lung adenocarcinoma (LUAD) causes millions of deaths annually worldwide. Parthenolide (PTL), extracted from traditional Chinese herbal medicines, has various biological activities. In this study, we investigated the effects of PTL on amino acid metabolism and oxidative stress in LUAD cells.Methods: This study identified differential proteins and potential mechanisms of action of PTL in LUAD cells through label-free quantitative proteomics and protein-protein interaction networks. Combined with targeted amino acid metabolomics, we confirmed the results of GO and KEGG analyses. On this basis, the potential targets of PTL in LUAD were identified through network pharmacology, molecular simulation docking, and molecular dynamics simulations. Finally, the effects of PTL on amino acid metabolism and oxidative stress in LUAD were verified using in vivo and in vitro experiments.Results: PTL treatment of LUAD cells resulted in significant changes in expression of 157 proteins. GO and KEGG enrichment analyses showed that these proteins were involved in amino acid metabolism and oxidative stress response. Targeted amino acid metabolomics further confirmed that PTL affected amino acid metabolism in LUAD.Network pharmacology, molecular docking, and molecular dynamics simulations identified GCTG as a potential target of PTL in LUAD. Meanwhile, in vitro and in vivo experimental results indicated that PTL targeting GCTG affected the proliferation, amino acid metabolism, and oxidative stress levels of LUAD cells.PTL affects proliferation, amino acid metabolism, and oxidative stress levels of LUAD cells via targeting GCTG. Therefore, our study provides new insights into the prevention and treatment of LUAD with PTL, which may lay the foundation for future research directions
Keywords: Lung Adenocarcinoma, Parthenolide, amino acid metabolism, Oxidative Stress, tumor
Received: 07 Jun 2025; Accepted: 31 Jul 2025.
Copyright: © 2025 Liu, Liu, Li and Shen. 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:
Jiye Liu, Jinzhou Medical University, Jinzhou, China
Shuang Shen, Jinzhou Medical University, Jinzhou, China
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