Potential Interaction of Propyl Gallate and Butylated Hydroxyanisole with EGFR–PI3K–Akt–mTOR Proteins in Oral and Gastrointestinal Carcinogenic Signaling Pathway: An in silico Molecular Docking Study

Abstract

BACKGROUND: Synthetic food preservatives are widely used to improve food stability and shelf life, but prolonged exposure may contribute to oral and gastrointestinal carcinogenesis. Epidermal growth factor receptor (EGFR)–phosphoinositide 3-kinase (PI3K)–protein kinase B (Akt)–mammalian target of rapamycin (mTOR) axis plays a pivotal role in regulating tumor initiation and progression; however, the potential interactions with cancer-related signaling proteins remain poorly understood. This study computationally evaluated the predicted binding interactions of commonly used synthetic food preservatives with proteins using molecular docking.

METHODS: Propyl gallate (PG), butylated hydroxyanisole (BHA), tertiary-butylhydroquinone (TBHQ), potassium sorbate (PS), sodium benzoate (SB), and sodium metabisulfite (SMB) were evaluated for physicochemical properties using SwissADME. Molecular docking with EGFR, PI3K, Akt-1, and mTOR was performed using CB-Dock 2.0. Predicted ligand–protein interactions were analyzed using BIOVIA Discovery Studio 2016 and root mean square fluctuation (RMSF) was evaluated using CABS-flex 3.0.

RESULTS: PG and BHA exhibited the most predicted binding affinities among the investigated preservatives. PG showed the strongest interactions with EGFR (−6.1 kcal/mol), PI3K (−6.8 kcal/mol), and mTOR (−6.7 kcal/mol), whereas BHA demonstrated the highest affinity toward PI3K (−6.8 kcal/mol) and Akt-1 (−6.5 kcal/mol). These interactions were supported by multiple hydrogen bonds, hydrophobic interactions, and van der Waals contacts.

CONCLUSION: PG and BHA exhibited the highest binding affinity toward proteins of the EGFR–PI3K–Akt–mTOR associated with oral and gastrointestinal carcinogenesis. These computational findings provide a basis for future experimental studies to determine the biological relevance of the predicted protein–ligand interactions under long-term dietary exposure.

KEYWORDS: synthetic food preservatives, molecular docking, oral carcinogenesis, gastrointestinal carcinogenesis