Resveratrol in Oral Squamous Cell Carcinoma: Preclinical Evidence and Translational Opportunities

Polyphenolic stilbenes are plant-derived compounds that have attracted increasing interest for their potential anticancer properties. Among them, resveratrol is the most extensively investigated molecule. Oral squamous cell carcinoma (OSCC) represents a major global health challenge due to its aggressive biological behavior, frequent late diagnosis, and limited improvement in survival outcomes despite advances in treatment. This review aims to summarize current experimental evidence on the anticancer effects of resveratrol in OSCC, also considering structurally related derivatives such as polydatin and pinostilbene hydrate. A structured review of the literature was performed to identify experimental studies investigating the activity of these compounds in OSCC models. Overall, the available evidence indicates that resveratrol exerts multiple antitumor effects in OSCC, including inhibition of cell proliferation, induction of apoptosis and ferroptosis, cell-cycle arrest, and suppression of migration, invasion, and epithelial–mesenchymal transition. These effects are associated with the modulation of several oncogenic signaling pathways and components of the tumor microenvironment. In addition, resveratrol has been reported to enhance the efficacy of chemotherapy, radiotherapy, and targeted therapies, and to counteract mechanisms of drug resistance. However, most findings derive from in vitro studies using concentrations that may not be readily achievable in vivo due to limited bioavailability. Further in vivo and clinical investigations are therefore required to clarify the translational potential of resveratrol in OSCC management.