Introduction: Colorectal cancer (CRC) is a formidable health challenge, often characterized by limited treatment success due to the development of drug resistance and high rates of cancer recurrence. Angiogenesis is a significant factor in cancer progression and metastasis that is known for its nourishment ability in pathophysiological conditions and is regulated by several proteins including vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and endocan (ESM-1). EGF affects cell behavior through its interaction with the receptor protein called EGFR which is a transmembrane protein that plays crucial roles in regulating cell differentiation, survival, proliferation, and angiogenesis. In the context of CRC, EGFR is frequently overexpressed, contributing to the survival, proliferation, and metastasis of cancer cells. This overexpression makes EGFR an attractive target for therapeutic intervention. Melatonin, a naturally occurring molecule renowned for its anticancer properties, has shown promise in impeding the progression of CRC by exerting inhibitory effects on EGFR. This emerging evidence underscores the potential of melatonin as a valuable component in the treatment of CRC. Moreover, in silico techniques, such as bioinformatics, molecular docking, and virtual screening, offer invaluable tools for investigating molecular interactions, thereby facilitating the process of drug discovery and development. By leveraging these advanced computational methods, researchers can gain comprehensive insights into potential therapeutic compounds and their interactions with specific targets, ultimately expediting the characterization and establishment of molecules and target proteins. These techniques not only accelerate the pace of research but also provide a robust framework for designing efficient in vitro and in vivo studies, thus significantly reducing the time required for comprehensive characterization and validation.
Methods: Durggability of the EGFR was assessed through the ProteinsPlus web portal. Vandetanib was selected as an approved EGFR inhibitor molecule from the drug bank database and the 3D structure of melatonin and vandetanib was extracted from PubChem. The 3D structures of the target protein and the selected molecules were reduced using the Ligprep and the Protein preparation wizard application from Schrodinger, EGFR was docked with both molecules using the Glide application from the Schrodinger software.
Results: Docking results proved that vindetanib couples with EGFR and melatonin can interact with the same pocket showing the tyrosine kinase inhibition potential of melatonin.
Conclusion: The results of this research emphasize the potential of melatonin as a treatment that can inhibit the activity of EGFR in colorectal cancer, working alongside current treatments such as vandetanib. Through computational analysis, it was discovered that melatonin binds to the same active site on the EGFR as vandetanib, indicating its ability to potentially inhibit its tyrosine kinase activity, which is crucial for the proliferation and survival of cancer cells. This study validates the molecular interaction between melatonin and EGFR, providing promising insights into the use of natural compounds as supplementary treatments to target EGFR in colorectal cancer. Additionally, the research showcases the effectiveness of computational methods such as bioinformatics and molecular docking in accelerating the discovery of potential therapeutic compounds, thereby reducing the necessity for extensive in vitro and in vivo experiments. Future research should concentrate on further confirming these findings through experimental studies, potentially opening the door for innovative melatonin-based therapeutic approaches in addressing drug-resistant and recurrent colorectal cancer. Future studies may consider other angiogenic proteins such as VEGFR and endocan that show important roles in cancer progression and metastasis.