Molecular Mechanisms of Melatonin for Treating Medullary Thyroid Cancer Using in silico Analysis

Melatonin is a neuroendocrine hormone that regulates various biological functions. The objective of this work was to conduct a thorough assessment of the molecular targets of melatonin for the treatment of medullary thyroid carcinoma (MTC) via bioinformatics methods. The identification of target proteins for melatonin and MTC was accomplished through the utilization of many databases. A total of 359 gene targets were acquired, then subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The GO subjects indicated a strong association in kinase activity and receptor-ligand activity between the target genes. On the other hand, the KEGG enrichment analysis indicated a significant involvement of the target genes in the PI3K/AKT and MAPK signaling pathways. To identify key genes, an initial step involved the construction of a protein-protein network using the intersecting targets. Subsequently, Cytoscape software unveiled TP53, STAT3, AKT1, JUN, and IL6 as hub genes within the network. The interaction of melatonin and hub genes was validated by molecular docking analysis. The results indicated that melatonin had high binding affinities towards all of the hub genes, with the exception of JUN. The interaction of melatonin and AKT1 had -10.54 kcal/mol binding free energy with several H-bonds and hydrophobic interactions. Also, the melatonin/p53 complex revealed low binding free energy (-9.95 kcal/mol) with strong H-bond interactions. All the outcomes suggest that melatonin induces apoptosis in MTC cells through the PI3K/AKT and MAPK signaling pathways. Therefore, melatonin has the potential to serve as a powerful therapeutic drug for the treatment of MTC.