In silico prediction of the action of bromelain on PI3K/Akt signalling pathway to arrest nasopharyngeal cancer oncogenesis by targeting phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha protein

• Published in: BMC research notes 2024-11, Vol.17 (1), p.346-8, Article 346
• Main Authors: Shamsuri, Alyaa Syafiqah, Sim, Edmund Ui-Hang
• Format: Article
• Language: English
• Subjects: Analysis; beta Catenin - metabolism; Bromelain; Bromelains - chemistry; Bromelains - pharmacology; Carcinogenesis - drug effects; Carcinogenesis - metabolism; Care and treatment; Catalytic Domain - drug effects; Class I Phosphatidylinositol 3-Kinases - metabolism; Computer Simulation; Diagnosis; ErbB Receptors - metabolism; Health aspects; Humans; Molecular Docking Simulation; Nasopharyngeal cancer; Nasopharyngeal carcinoma; Nasopharyngeal Neoplasms - drug therapy; Nasopharyngeal Neoplasms - metabolism; Nasopharyngeal Neoplasms - pathology; Phosphatidylinositol 3-Kinases - metabolism; PIK3CA; Pineapple; Protein Binding - drug effects; Protein-protein interactions; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Research Note; Signal Transduction - drug effects; TOR Serine-Threonine Kinases - metabolism
• ISSN: 1756-0500; 1756-0500
• DOI: 10.1186/s13104-024-06995-2

This research investigates the potential anti-tumour effects of bromelain, an aqueous extract from pineapple stems and fruits, on nasopharyngeal cancer (NPC). While bromelain is known for its medicinal properties in various cancers, its impact on NPC remains unexplored. Using in silico methods, we studied the predicted interactions between bromelain and key proteins involved in NPC oncogenesis, specifically β-catenin, PIK3CA, mTOR, EGFR, and BCL2. Molecular docking strategies were performed using a myriad of computational tools. A 3D model of bromelain was constructed using SWISS-MODEL, followed by molecular docking simulations performed with ClusPro. The binding affinities of the docked complexes were evaluated using HawkDock, and the interactions were analysed with LigPlot+. The docking scores indicated potential spontaneous interactions, with binding affinities based on being - 103.89 kcal/mol (PIK3CA), -73.16 kcal/mol (EGFR), -71.18 kcal/mol (mTOR), -65.22 kcal/mol (β-catenin), and - 57.48 kcal/mol (BCL2). LigPlot + analysis revealed the presence of hydrogen bonds, hydrophobic interactions, and salt bridges, indicating stable predicted interactions. Our findings suggest that bromelain can target key proteins involved in NPC oncogenesis, with the strongest affinity towards PIK3CA. This suggests a hypothetical insight into bromelain's anticancer effects on NPC through the modulation of the PI3K/Akt signaling pathway.