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

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