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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1448381

Integrating network pharmacology, molecular docking and experimental verification to reveal the mechanism of Artesunate in inhibiting Choroidal Melanoma

Provisionally accepted
Qingyue Ma Qingyue Ma 1Yichong Liu Yichong Liu 1Qian Zhang Qian Zhang 1Yi Wendan Yi Wendan 1Ying Sun Ying Sun 2Xiaodi Gao Xiaodi Gao 1Xintong Zhao Xintong Zhao 1Haowen Wang Haowen Wang 1Ke Lei Ke Lei 3*Wenjuan Luo Wenjuan Luo 1*
  • 1 Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, China, Qingdao, China
  • 2 Ophthalmology department，Qingdao Central Hospital, University of Health and Rehabilitation Sciences（Qingdao Central Hospital）, Qingdao, China
  • 3 Tumor Immunology and Cytotherapy of Medical Research Center and Key Laboratory of Pancreatic Disease Clinical Research (Shandong Province), The Affiliated Hospital of Qingdao University, Qingdao, China

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

    Background: Artesunate (ART) from Artemisia annua shows potential in treating various tumors, including choroidal melanoma (CM), a malignant ocular tumor with poor prognosis and limited treatment options. Methods: Potential ART targets were identified using PubChem, Swiss Target Prediction and TCMSP databases. CM-related genes were selected from OMIM, GeneCards and DisGeNET databases. Intersection targets underwent PPI network analysis and GO/KEGG pathway analysis. Molecular docking predicted ART-target interactions. ART's effects on CM were evaluated through CCK8, colony formation, transwell, flow cytometry and Western blot assays. In vivo assays on subcutaneous tumors in nude mice validated ART's effects. Results: Network pharmacology identified key pathways and core targets for ART in CM treatment. Molecular docking confirmed strong ART-target binding. In vitro assays showed ART inhibited CM cell proliferation and migration by promoting apoptosis via the p53 pathway, causing cell cycle arrest at G0/G1 by inhibiting PI3K/AKT/mTOR and increasing ROS via the NRF2/HO-1 pathway. In vivo assays confirmed ART's anti-proliferative effects on CM. Conclusion: ART demonstrated significant anti-cancer effects on CM by promoting apoptosis, inducing cell cycle arrest and increasing ROS levels, suggesting therapeutic potential for CM.

    Keywords: Artesunate, Choroidal melanoma, Anti-cancer mechanism, Network Pharmacology, molecular docking

    Received: 13 Jun 2024; Accepted: 24 Jul 2024.

    Copyright: © 2024 Ma, Liu, Zhang, Wendan, Sun, Gao, Zhao, Wang, Lei and Luo. 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:
    Ke Lei, Tumor Immunology and Cytotherapy of Medical Research Center and Key Laboratory of Pancreatic Disease Clinical Research (Shandong Province), The Affiliated Hospital of Qingdao University, Qingdao, China
    Wenjuan Luo, Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, China, Qingdao, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.