Abstract
Apigenin, a flavonoid, has shown early promise in colon cancer (CC); thus, exploring potential mechanisms of Apigenin is obligatory. In this study, shared targets of Apigenin and CC were identified through online tools, which were then subjected to functional enrichment analyses, Gene Ontology and KEGG. Further, the protein-protein interaction network of the shared targets was developed (via STRING). The top targets of Apigenin in CC were identified by molecular docking; further investigated for differential gene and protein expression in CC and their influence on CC patient survival (using TCGA data). Out of 13 hub genes, the top 3 targets (HSP90AA1, MMP9, PTGS2) were selected based on docking score. Their expression was significantly elevated and related to poor overall survival in CC (except PTGS2). Molecular dynamics simulation further validated protein-ligand interactions and divulged HSP90AA1 as the best target of Apigenin in CC. Finally, the anti-cancer effects of Apigenin and its major metabolite, luteolin, were investigated in CC, which is involved in the cytotoxicity of CC cells (COLO-205) by reducing HSP90AA1 expression revealed by real-time PCR. Thus, HSP90AA1 was identified as one of the prime targets of Apigenin in CC, and Apigenin could be effective against CC.
Communicated by Ramaswamy H. Sarma
Acknowledgements
The authors greatly acknowledge the help of the MAKAUT, WB authority, for providing the necessary support.
Authors’ contributions
AS and DN conceived the idea, and designed experiments. AS TK and DK curated Data, DN, and AS prepared the original draft. AS DK and TK performed in silico experiments and data analysis. AS performed in vitro experiments. AS TK and DK prepared the figures. AS wrote the final Manuscript and DN critically reviewed it. DN supervised the Project.
Disclosure statement
No potential conflict of interest was reported by the authors.