The Natural Antioxidant Shield of α-Tocopherol from <em>Stichopus hermanii </em>Against Oral Squamous Cell Carcinoma: A Scoping Review
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Background: Oral squamous cell carcinoma (OSCC) is a major global health burden, with high recurrence and therapeutic resistance. α-Tocopherol, the most active form of vitamin E and a potent antioxidant, occurs in Stichopus hermanii together with other bioactive compounds. These natural agents have been proposed as adjunctive strategies with dual antioxidant and anticancer potentials. Objective: To map evidence of the antioxidant and anticancer activities of α-tocopherol, either as an isolated compound or within S. hermanii extracts, against molecular targets in OSCC. Methods: A scoping review was conducted according to the PRISMA-ScR guidelines. Searches in PMC, PubMed, ScienceDirect, ResearchGate, and Google Scholar (until July 2025) identified English- or Indonesian-language Scopus-indexed full-text studies. Eligible reports included original in vitro, in vivo, and clinical investigations of α-tocopherol and S. hermanii in OSCC models. Data on the design, interventions, molecular targets, and outcomes were charted and narratively synthesized. Results: Five studies were included (three in vitro, one in vivo, and one clinical study). In vitro, α-tocopherol decreased OSCC cell viability and induced apoptosis via caspase activation, Bax upregulation, and Bcl-2 suppression, with synergistic effects observed with combination therapy. In vivo, α-tocopherol upregulated PPARγ and inhibited PI3K/Akt signalling, whereas S. hermanii extract reduced oxidative stress. Clinically, supplementation during radiotherapy improves the oxidative balance. Common molecular targets include apoptotic regulators and oxidative stress markers; however, OSCC-specific oncogenic pathways remain unexplored. Conclusion: α-Tocopherol exhibits antioxidant and pro-apoptotic effects in OSCC, indicating its potential as an adjunct therapy. However, the evidence is limited and heterogeneous, necessitating standardized interventions and clinical trials to confirm these findings.