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European journal of pharmacology

European journal of pharmacology

IF: 4.2
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Luteolin Targets Peroxiredoxin 2 to Augment T-Cell-Mediated Cytotoxicity and Suppress Lung Adenocarcinoma Progression

Published:23 July 2025 DOI: 10.1016/j.ejphar.2025.177984 PMID: 40712879
Xuan Li , Ying Bai , Jiawei Zhou , Anqi Cheng , Jianqiang Guo , Maoqian Chen , Dong Hu , Jing Wu

Abstract

Lung adenocarcinoma (LUAD), as a prevalent and life-threatening malignancy, poses a significant global health burden, particularly impacting patients and their families profoundly. Peroxiredoxin-2 (PRDX2) exhibits high expression levels in LUAD tissues. However, the identification of efficient and low-toxicity small-molecule inhibitors targeting PRDX2 from traditional Chinese medicine remains a challenging task. This study aims to identify potential inhibitors of PRDX2 in lung adenocarcinoma and elucidate their mechanism of action. Molecular docking and thermal shift assays were employed to evaluate the interaction between luteolin and PRDX2 protein. The effects of luteolin on lung cancer cell behavior were assessed through in vitro cellular experiments, and its efficacy on tumor growth was validated in a mouse model. Additionally, flow cytometry and Western blot analysis were utilized to investigate the mechanism of luteolin's action. Molecular docking and thermal shift experiments confirmed the binding affinity of luteolin to PRDX2. In vitro experiments demonstrated that luteolin significantly inhibits the proliferation and migration of LUAD cells. In vivo experiments showed that luteolin effectively suppresses tumor growth in an immunocompetent lung cancer mouse model. Western blot results untangled that luteolin promotes apoptosis of lung cancer cells by enhancing T-cell-mediated killing pathways via PRDX2. In summary, luteolin binds to PRDX2, inhibiting the JAK2/STAT3 pathway, suppressing PD-L1 expression, promoting the release of perforin and granzyme B from CD8+ T cells, and inhibiting immune evasion in LUAD, thereby inhibiting the progression of lung adenocarcinoma.

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