Abstract 613: Investigating cyclooxygenase isoforms as targets for anticancer compounds isolated from Tulbaghia violacea

Abstract Introduction: The medicinal plant Tulbaghia violacea exhibits anticancer properties in triple-negative breast cancer (TNBC) cells, primarily through apoptosis induction. Transcriptomic analyses of treated TNBC cells highlighted altered expression of cyclooxygenase isoforms COX-1 and COX-2. COX-1, with anti-apoptotic properties, is associated with tumor progression, while COX-2, with pro-apoptotic properties, acts as a tumor suppressor. Methods: Bioactive compounds derived from T. violacea were screened for their potential interaction with cyclooxygenase isoforms using molecular docking approaches. Protein structures for COX-1 (PDB: 6Y3C) and COX-2 (PDB: 5IKT) were retrieved from the Protein Data Bank. Ligand and protein preparation for sixteen compounds was conducted using the Schrödinger Suite. Standard precision (SP) docking was followed by MM-GBSA post-docking and extra precision (XP) docking to refine binding affinity predictions. Results and Discussion: COX-2 demonstrated the highest average docking scores, indicating stronger binding affinity for the T. violacea-derived compounds. Comparative structural analysis revealed significant differences in binding site residues and global backbone structures between COX-1 and COX-2. SiteMap analysis identified the most druggable regions, with COX-2’s larger binding pocket enabling higher binding affinity. Notably, the same compounds were capable of binding both isoforms, although with lower affinity for COX-1. These findings suggest that the anticancer activity of T. violacea compounds may be mediated by their preferential binding to COX-2, which is often upregulated in cancers. Conclusion : This study highlights the potential of Tulbaghia violacea as a source of bioactive compounds targeting cyclooxygenase isoforms, particularly COX-2. The preferential binding to COX-2 aligns with its pro-apoptotic role and its upregulation in cancers, underscoring its relevance in cancer therapy. Further experimental validation is warranted to confirm these in silico findings and to explore the therapeutic potential of T. violacea-derived compounds. Citation Format: Zodwa Dlamini, Rodney Hull, Mohammed Alaouna. Investigating cyclooxygenase isoforms as targets for anticancer compounds isolated from Tulbaghia violacea [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 613.