In silico molecular docking, molecular dynamics, ADMET analysis of fucoidan against receptor frizzled-8 and coreceptor LRP6 in Wnt/β-Catenin pathway and in vitro analysis of fucoidan extract from Sargassum echinocarpum as β-catenin inhibitor in breast cancer cell line (MCF-7)

• Published in: Journal of biomolecular structure & dynamics 2024-12, Vol.42 (21), p.11828-11843
• Main Authors: Laeliocattleya, Rosalina Ariesta, Yunianta, Yunianta, Risjani, Yenny, Wulan, Siti Narsito
• Format: Article
• Language: English
• Subjects: anticancer; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; beta Catenin - metabolism; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Proliferation - drug effects; Female; Frizzled Receptors - antagonists & inhibitors; Frizzled Receptors - metabolism; Fucoidan; Humans; Low Density Lipoprotein Receptor-Related Protein-6 - metabolism; MCF-7 Cells; molecular docking; Molecular Docking Simulation; molecular dynamics; Molecular Dynamics Simulation; Plant Extracts - chemistry; Plant Extracts - pharmacology; Polysaccharides - chemistry; Polysaccharides - pharmacology; Protein Binding; Wnt Signaling Pathway - drug effects; β-catenin
• ISSN: 0739-1102; 1538-0254; 1538-0254
• DOI: 10.1080/07391102.2023.2265488

This study aimed to investigate the effect of fucoidan on the Wnt/β-Catenin pathway using both in-silico molecular docking, molecular dynamics, ADMET analysis (in frizzled-8 receptor and LRP6 coreceptor) and in-vitro experiments using MCF-7 breast cancer cells. Through the molecular docking analysis, the binding energies on the frizzled-8 receptor were −5.6, −5.1, −9.4, and −8.8 kcal/mol, respectively. Meanwhile, those on the LRP6 receptor, were −7.3, −6.2, −10.0, and −9.8 kcal/mol, respectively. The results showed that fucoidan had a favorable binding affinity for both receptors. Furthermore, it was discovered to reduce the interaction and binding affinity between Wnt agonists to frizzled-8 and LRP6 receptors. This reduction was reflected in the change in the binding energy of the fucoidan-Wnt agonist-frizzled 8 and fucoidan-Wnt agonist-LRP6 complexes, which exhibited decreases of −7.0 kcal/mol and −7.8 kcal/mol, respectively. Fucoidan was found stable in complexes with frizzled-8 receptor and co-receptor LRP6. ADMET study showed it's non-carcinogenic and can be distributed in the body. Fucoidan effectively inhibited β-catenin production, a critical factor in the Wnt/β-catenin pathway. The MCF-7 breast cancer cells were treated with fucoidan extract from S. echinocarpum at incubation times of 24, 48, and 72 h, resulting in a reduction of β-catenin levels by 95.19%, 83.88%, and 80.88%, respectively. Fucoidan also shows no significant difference in value compared to fucoidan standard (F. vesiculosus) and doxorubicin. Fucoidan exhibited antiproliferative effects against breast cancer cells, specifically through its modulation of the Wnt/β-Catenin pathway, and held great potential as an herbal anticancer agent. Communicated by Ramaswamy H. Sarma