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Taming Pancreatic Cancer: Ardisia virens Kurz-Derived 4-Hydroxy-2-Methoxy-6-Tridecylphenyl Acetate as a Potent Tubulin Polymerization Inhibitor for Targeted Pancreatic Ductal Adenocarcinoma Therapy
期刊文章

Taming Pancreatic Cancer: Ardisia virens Kurz-Derived 4-Hydroxy-2-Methoxy-6-Tridecylphenyl Acetate as a Potent Tubulin Polymerization Inhibitor for Targeted Pancreatic Ductal Adenocarcinoma Therapy

C.-H. Yen, C.-J. Lin, P.-Y. Chen, Y.-J. Chen, L.-R. Wei, P.-H. Chen, Y.-C. Yeh, L.H.-C. Wang, H.-S. Chang 和 W.-C. Tsai
International Journal of Medical Sciences, 卷.22(3), 頁碼.651-661
2025
Web of Science ID: WOS:001454764300014

摘要

4-hydroxy-2-methoxy-6-tridecylphenyl acetate Ardisia virens Kurz pancreatic ductal adenocarcinoma Animals Apoptosis Carcinoma, Pancreatic Ductal Cell Line, Tumor Cell Proliferation Humans Mice Molecular Docking Simulation Pancreatic Neoplasms Plant Extracts Tubulin Tubulin Modulators Xenograft Model Antitumor Assays 4 hydroxy 2 methoxy 6 tridecylphenyl acetate annexin antineoplastic agent caspase 3 tubulin tubulin modulator unclassified drug plant extract tubulin animal experiment animal tissue antineoplastic activity apoptosis Ardisia Ardisia virens Article BxPC-3 cell line cell enucleation controlled study drug cytotoxicity drug effect G2 phase cell cycle checkpoint human human cell in vitro study male molecular docking molecular interaction molecularly targeted therapy mouse nonhuman PANC-1 cell line pancreatic ductal carcinoma protein polymerization tumor growth tumor xenograft animal apoptosis cell proliferation chemistry drug screening drug therapy metabolism pancreas tumor pancreatic ductal carcinoma pathology tumor cell line
Pancreatic ductal adenocarcinoma (PDAC) is a major global health challenge owing to late diagnosis and inherently metastatic nature. Although surgical intervention offers a potential remedy, only few patients are eligible, and drug resistance further complicates treatment. The therapeutic limitations have catalyzed a search for alternative treatments, particularly natural products. High-throughput screening identified six extracts from the Ardisia genus, with four from Ardisia virens Kurz, and 4-hydroxy-2-methoxy-6-tridecylphenyl acetate (HMTA) as the most potent candidate. Herein, we explored the anti-cancer effects of HMTA on PDAC and found it induced strong cytotoxic effects on BxPC-3 and PANC-1 pancreatic cancer cell lines. HMTA inhibited cell proliferation and induced apoptosis, as evidenced by annexin V/PI labeling and caspase 3 activation. HMTA halted cancer cell proliferation at the G2/M phase and induced multinucleation. Molecular docking analysis revealed that HMTA potentially could interact with tubulin, and in vitro assay confirmed it suppresses tubulin polymerization. HMTA significantly inhibited BxPC-3 xenograft tumor growth in mice. Overall, these findings suggested that HMTA is a promising candidate for PDAC therapy. © The author(s).

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https://www.scopus.com/inward/record.uri?eid=2-s2.0-85216961453&doi=10.7150%2fijms.104112&partnerID=40&md5=5cfde098d70e1df100cad531a82d4032檢視
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https://doi.org/10.7150/ijms.104112檢視
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