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.

Abstract

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.