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

Ferry Sandra (Department of Biochemistry and Molecular Biology, Division of Oral Biology, Faculty of Dentistry, Universitas Trisakti, Jl. Kyai Tapa No. 260, Jakarta 11440)
Visi Endah Pratitis (The Prodia Education and Research Institute, Jl. Kramat Raya No. 150, Jakarta, 10430)
Dewi Priandini (Department of Oral Medicine, Faculty of Dentistry, Universitas Trisakti, Jl. Kyai Tapa No. 260, Jakarta 11440)
Andrian Nova Fitri (Department of Oral Medicine, Faculty of Dentistry, Universitas Trisakti, Jl. Kyai Tapa No. 260, Jakarta 11440)
Maria Leny Raiyon (Department of Oral Medicine, Faculty of Dentistry, Universitas Trisakti, Jl. Kyai Tapa No. 260, Jakarta 11440)
Kyung Hoon Lee (Research Institute, Ballys Co. Ltd, Incheon 22219)

The Indonesian Biomedical Journal
Vol 18, No 4 (2026)

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