Computational evaluation of bioactive compounds from Vitis vinifera as a novel β-catenin inhibitor for cancer treatment

• Published in: Bulletin of the National Research Centre 2022-06, Vol.46 (1), p.1-9, Article 183
• Main Authors: Adebesin, Ayomide Oluwadarasimi, Ayodele, Abigail Oluwakemi, Omotoso, Olabode, Akinnusi, Precious Ayorinde, Olubode, Samuel Olawale
• Format: Article
• Language: English
• Subjects: ADMET; Amino acids; Anticancer properties; Apoptosis; Binding sites; Bioactive compounds; Bioinformatics; Biological activity; Breast cancer; Cancer therapies; Cell cycle; Cell differentiation; Cell growth; Cell proliferation; Colorectal cancer; Colorectal carcinoma; Computer applications; Drug development; Flavonoids; Humanities and Social Sciences; Inhibitors; Metabolism; MM/GBSA; Molecular docking; multidisciplinary; Mutation; Pharmaceutical Industries; Pharmacophore modeling; Phenols; Rutin; Science; Science (multidisciplinary); Signal transduction; Signaling; Therapeutic targets; Vitis vinifera; Wnt protein; Wnt/β-catenin signaling pathway; β-Catenin
• ISSN: 2522-8307; 2522-8307
• DOI: 10.1186/s42269-022-00872-3

Background β-catenin is an important unit of the Wnt/β-catenin signaling pathway, a conserved process involving several physiological activities, encompassing differentiation and cell proliferation, etc. The dysfunction or mutation in β-catenin causing the initiation and advancement of various neoplasm types, including colorectal cancer, breast cancer, etc., has been reported. Therefore, β-catenin is a therapeutic target. Hence, designing new inhibitors targeted against β-catenin will prevent cancerous cells’ involvement and eliminate the diseases. Studies showed that Vitis vinifera , a well-known grape species, contains different phytochemical substances, including aromatic acids, flavonoids, phenolic compounds, proanthocyanins, etc. V.vinifera exerts different anticancer properties such as apoptosis, cell proliferation, cell cycle arrest, and inhibition in cancerous cells. Structural bioinformatics methods, including molecular docking, molecular mechanics generalized Born surface area (MM/GBSA), absorption, distribution, metabolism, excretion studies (ADMET), and pharmacophore modeling approach, were used to determine the potential β-catenin inhibitors from V.vinifera bioactive compounds. Result Cis-astringin, rutin, caftaric acid, trans-caftaric acid, procyanidin B3, cis-Miyabenol C, and ampelopsin H are shown to be suitable inhibitors against β-catenin due to their binding affinity and interaction with the amino acids residues at the binding sites of β-catenin compared to Food and Drug Administration (FDA) approved drugs leucovorin Calcium and Xeloda prescribed to cure colorectal cancer. Conclusions This study suggests that V. vinifera could be a good plant source for compounds that might treat cancer by inhibiting the Wnt/β-catenin signaling pathway.