Targeting the MAPK pathway in skin cancer using extra virgin olive oil phytochemicals: An integrative computational study

Abstract

The malfunction of the mitogen-activated protein kinase (MAPK) signaling pathway, particularly in melanoma, makes skin cancer one of the biggest health risks in the world. The treatment that uses well-known therapeutic strategies to target important kinases like BRAF and MEK is still working. Extra virgin olive oil (EVOO) is an important part of the Mediterranean diet and is a good source of phenolic phytochemicals that fight cancer. In this context, the present study aims to explore the possible anticancer effects of EVOO on skin cancer. Utilizing an integrative computational approach, we aim to assess the inhibitory efficacy of twenty phytochemical compounds from EVOO on BRAF and MEK, two key proteins of the MAPK pathway. We used in silico molecular docking and relevant ADMET descriptors to find out how well several phytochemicals bind to the active sites of both receptors. Among these, apigenin and ligstroside demonstrated the best interaction profiles with MEK and BRAF, respectively. The chosen compounds exhibited a satisfactory pharmacokinetic profile based on the ADME-Tox assessment. 200 ns molecular dynamics simulations were performed to evaluate the structural integrity of the protein–ligand complexes, which were found to be stable. Their electronic reactivity and interaction capability were further corroborated by density functional theory (DFT) calculations. In summary, these findings suggest that EVOO phytochemicals may contribute to inhibiting MAPK pathway-associated skin cancer and might serve as promising candidates for new therapeutic strategies against this disease.