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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1545779
This article is part of the Research Topic Herbal Medicines’ Safety and Clinical Application: New Strategies for Overcoming Therapeutic Challenges View all 5 articles

Luteolin Inhibits Diffuse Large B-cell Lymphoma Cell Growth through the JAK2/STAT3 Signaling Pathway

Provisionally accepted
Xin-Zhuo Zhan Xin-Zhuo Zhan 1,2Yi-Wen Bo Yi-Wen Bo 3Yu Zhang Yu Zhang 4Hai-Dong Zhang Hai-Dong Zhang 1Shang Zhihao Shang Zhihao 5Hui Yu Hui Yu 1Xiao-Li Chen Xiao-Li Chen 1Xiang-Tu Kong Xiang-Tu Kong 1Wanzhou Zhao Wanzhou Zhao 6Timo Teimonen Timo Teimonen 7Tao Liu Tao Liu 4Meng-Yi Lu Meng-Yi Lu 8*Ye Yang Ye Yang 3*Shang Zhihao Shang Zhihao 9*Haiwen Ni Haiwen Ni 1*
  • 1 Department of Hematology, Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Liaoning Province, China
  • 2 School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
  • 3 School of Artificial Intelligence and Information Technology, Nanjing University of Traditional Chinese Medicine, Nanjing, Liaoning Province, China
  • 4 School of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Liaoning Province, China
  • 5 Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, Beijing Municipality, China
  • 6 The Nanjing Han & Zaenker Cancer Institute (NHZCI), OG Pharmaceuticals, 88 Jiangdong Road, Nanjing, China
  • 7 Aqsens Health Oy, Itäinen Pitkäkatu 4B, Turku, Finland
  • 8 Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, China
  • 9 Nanjing University of Chinese Medicine, Nanjing, China

The final, formatted version of the article will be published soon.

    Luteolin, a flavonoid present in botanical drugs, plants, and dietary sources, has demonstrated anticancer properties against various tumors, yet its role in diffuse large B-cell lymphoma (DLBCL) remains unclear. This study aimed to uncover the molecular mechanism of luteolin in DLBCL treatment using a combination of in vitro and in vivo experiments and computational analysis. Human DLBCL cell lines U2932 and OCI-LY10 were utilized to assess luteolin's impact on cell growth, apoptosis, cell cycle progression, and the modulation of JAK2/STAT3 pathway proteins. In vivo, a U2932 tumor-bearing nude mice model was employed to evaluate luteolin's antitumor efficacy and its effects on JAK2/STAT3 pathway protein expression. Additionally, molecular dynamics simulations were conducted to explore the interaction between luteolin and JAK2. The findings revealed that luteolin significantly suppressed cell proliferation, induced apoptosis, and arrested the cell cycle at the G2/M phase in both cell lines. In the mouse model, luteolin effectively inhibited tumor growth and downregulated the expression of phosphorylated JAK2 and STAT3 without altering the total protein levels of JAK2 and STAT3. Computational analysis indicated stable binding of luteolin to JAK2. Collectively, these results suggest that luteolin's anti-DLBCL activity may be mediated through the regulation of the JAK2/STAT3 signaling pathway, positioning it as a potential therapeutic agent for DLBCL.

    Keywords: Luteolin, Diffuse large B-cell lymphoma, Janus kinase 2/signal transducer and activator of transcription 3, Mechanism, Traditional Chinese Medcine

    Received: 15 Dec 2024; Accepted: 31 Jan 2025.

    Copyright: © 2025 Zhan, Bo, Zhang, Zhang, Zhihao, Yu, Chen, Kong, Zhao, Teimonen, Liu, Lu, Yang, Zhihao and Ni. 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:
    Meng-Yi Lu, Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu Province, China
    Ye Yang, School of Artificial Intelligence and Information Technology, Nanjing University of Traditional Chinese Medicine, Nanjing, 210023, Liaoning Province, China
    Shang Zhihao, Nanjing University of Chinese Medicine, Nanjing, China
    Haiwen Ni, Department of Hematology, Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210017, Liaoning Province, China

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