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Drug Res (Stuttg)
DOI: 10.1055/a-2724-9894
Original Article

Gallic Acid Induces Apoptosis in Oral Squamous Cell Carcinoma via PI3K/AKT/mTOR Pathway Inhibition and PTEN Upregulation: an In Vitro Study

Authors

  • Sanaz Helli

    1   Department of Oral Medicine, TaMS.C., Islamic Azad University, Tabriz, Iran (the Islamic Republic of) (Ringgold ID: RIN201583)

  • Armin Heidari

    1   Department of Oral Medicine, TaMS.C., Islamic Azad University, Tabriz, Iran (the Islamic Republic of) (Ringgold ID: RIN201583)

  • Armin Tafvizi

    1   Department of Oral Medicine, TaMS.C., Islamic Azad University, Tabriz, Iran (the Islamic Republic of) (Ringgold ID: RIN201583)

  • Amir Valizadeh 

    2   Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran (the Islamic Republic of) (Ringgold ID: RIN48432)

  • Sona Rafieyan

    2   Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran (the Islamic Republic of) (Ringgold ID: RIN48432)

  • Bahman Yousefi 

    3   Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran (the Islamic Republic of) (Ringgold ID: RIN48432)

Tabriz University approves this paper in the Medical Sciences.
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Abstract

Introduction

Oral squamous cell carcinoma is one of the most common head and neck cancers, which is associated with drug resistance and high mortality rates. The PI3K/AKT/mTOR pathway plays a crucial role in the survival, growth, and metastasis of cancer cells, making it a suitable target for targeted therapy.

Objective

This study investigated the antitumor effects of gallic acid on CAL-27 cells, with a focus on the aforementioned pathway.

Methods

CAL-27 cells were treated with different concentrations of gallic acid for 48 hours, and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to assess viability. The expression of key genes and proteins in the PI3K/AKT/mTOR pathway, as well as apoptosis-related genes, was evaluated using the quantitative real-time reverse transcription polymerase chain reaction and western blot. Also, the activity of caspase-3/7 enzymes and the level of apoptosis were measured by fluorometric methods and enzyme-linked immunosorbent assay.

Results

Gallic acid significantly decreased oral squamous cell carcinoma cell viability in a dose- and time-dependent manner. The expression of PI3K, AKT, and mTOR genes and proteins was decreased, while PTEN expression was increased. Also, the increase in Bax expression and caspase activity indicated a strong induction of apoptosis by gallic acid.

Conclusions

Gallic acid exhibits significant anticancer effects in oral squamous cell carcinoma cells by inhibiting the PI3K/AKT/mTOR pathway and activating apoptotic pathways. This natural compound may contribute to the development of targeted therapies for oral cancer, pending further preclinical validation.

Keywords

Gallic acid - oral squamous cell carcinoma - PI3K/AKT pathway - apoptosis


Publication History

Received: 23 August 2025

Accepted after revision: 13 October 2025

Article published online:
26 November 2025

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