2. Academic Validation
  3. Luteolin targets peroxiredoxin 2 to augment T-cell-mediated cytotoxicity and suppress lung adenocarcinoma progression

Luteolin targets peroxiredoxin 2 to augment T-cell-mediated cytotoxicity and suppress lung adenocarcinoma progression

  • Eur J Pharmacol. 2025 Oct 5:1004:177984. doi: 10.1016/j.ejphar.2025.177984.
Xuan Li 1,  Ying Bai 2,  Jiawei Zhou 3,  Anqi Cheng 1,  Jianqiang Guo 1,  Maoqian Chen 1,  Dong Hu 4,  Jing Wu 5
Affiliations

Affiliations

  • 1 School of Medicine, Anhui University of Science and Technology, Huainan, 232000, Anhui, China; Anhui Occupational Health and Safety Engineering Laboratory, Huainan, 232000, Anhui, China.
  • 2 School of Medicine, Anhui University of Science and Technology, Huainan, 232000, Anhui, China; Anhui Occupational Health and Safety Engineering Laboratory, Huainan, 232000, Anhui, China. Electronic address: by0319_cpu@163.com.
  • 3 Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, AUST, Huainan, 232001, China.
  • 4 The First Affiliated Hospital of Anhui University of Science and Technology Huainan First People's Hospital, School of Medicine, Huainan, 232000, Anhui, China; Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 232001, Anhui, China. Electronic address: dhu@aust.edu.cn.
  • 5 The First Affiliated Hospital of Anhui University of Science and Technology Huainan First People's Hospital, School of Medicine, Huainan, 232000, Anhui, China; The Affiliated Bozhou Hospital of Anhui University of Science and Technology (The People's Hospital of Bozhou). Bozhou, 236800, Anhui, China. Electronic address: aust_jingwu@aust.edu.cn.
PMID: 40712879 DOI: 10.1016/j.ejphar.2025.177984
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.

Keywords

Lung adenocarcinoma; Luteolin; Peroxiredoxin 2; T cell.

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