Inhibition of GATA3, ABCB1, and TYR by gallic acid: A real-world approach to uncovering a preventive agent against oral squamous cell carcinoma development

• Published in: Gene reports Vol. 33; p. 101840
• Main Authors: Guimarães, Osvaldo Sena, Cangussu, Lílian Mendes Borburema, dos Reis Pereira Queiroz, Lorena, Santos, Eliane Macedo Sobrinho, de Souza, Marcela Gonçalves, de Paula, Alfredo Maurício Batista, Farias, Lucyana Conceição, Santos, Sérgio Henrique Sousa, D'Angelo, Marcos Flávio Silveira Vasconcelos, Guimarães, André Luiz Sena
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.12.2023
• Subjects: Antineoplastic action; Antioxidant effect; Head and neck cancer; HSP90; Oral squamous cell carcinoma; Polyphenols; 4NQO; OSCC; HSP90; SERPINE1 (PDB ID: 9PAI); UGT2B17; Antioxidant effect; Oral squamous cell carcinoma; CASP3 (PDB ID: 5IBC); GEO; DEGs; ABCB1 (PDB ID: 6QEX); MMP2 (PDB ID: 1HOV); EIF2AK3 (PDB ID: 5V1D); JUN (PDB ID: 1JUN); NCBI; Polyphenols; TYR (PDB ID: 2Y9X); Head and neck cancer; ATM; GA; Antineoplastic action; GATA3 (PDB ID: 4HC9); PMOL
• ISSN: 2452-0144; 2452-0144
• DOI: 10.1016/j.genrep.2023.101840

This study aimed to the efficacy of gallic acid (GA) as a prospective prophylactic agent against the onset of oral squamous cell carcinoma (OSCC). We conducted bioinformatic analyses to identify the molecular targets of GA. Subsequently, we employed the 4NQO-induced animal model to evaluate the therapeutic potential of GA in OSCC. Our analysis unveiled that only three genes, ABCB1, GATA3, and SERPINE1, were associated with survival outcomes in OSCC patients. Reduced expressions of ABCB1 and GATA3 correlated with hazard ratios of 1.53 and 2.06, respectively, for mortality, while elevated SERPINE1 expression carried a 1.42-fold increased risk of death in OSCC patients. Molecular docking simulations underscored the robust affinity between GA and these genes, revealing binding energies of −6.0 kcal/mol for ABCB1, − 6.1 kcal/mol for GATA3, and −5.9 kcal/mol for SERPINE1. Furthermore, GA treatment demonstrated statistically significant reductions in the histopathological grade of 4NQO-induced lesions (p = 0.006) and mitigated liver (p < 0.001) and kidney (p < 0.001) toxicity associated with 4NQO exposure. The current study highlights GA as a promising contender for OSCC prevention. Mainly, GA targets critical genes such as ABCB1, GATA3, and SERPINE1, substantially impacting patient survival. Furthermore, GA administration mitigates 4NQO-induced toxicity, indicating its potential to improve animal survival by reducing lesion severity. These findings carry significant implications for OSCC research and potential clinical applications. •GA targets reduced survival.•GA reduced OSCC incidence and 4NQO toxicity.•GA reduced OSCC death.