Naringenin in Oral Cancer Management: Molecular Targets, Antiproliferative Mechanisms, and Therapeutic Potential

Author

Muneeshwaran G; Dr. R. Prabhu; Antony Vincy S; Bhavani N; Ramprasath C


Abstract

 Oral cancer, of which oral squamous cell carcinoma (OSCC) accounts for the vast majority, remains a major global health burden, particularly in regions where tobacco, areca nut and alcohol use are widespread. Surgery, radiotherapy and platinum-based chemotherapy are associated with considerable morbidity, functional impairment, drug resistance and recurrence, which has stimulated interest in safer, mechanism-based adjuncts derived from natural products. Naringenin (4′,5,7-trihydroxyflavanone) is a citrus flavanone, and the aglycone of naringin, with reported antioxidant, anti-inflammatory and antineoplastic activities. In oral cancer models, naringenin has been shown to reduce cell viability and induce apoptosis through reactive oxygen species (ROS) generation, modulation of the Bid/Bcl-xL axis and endoplasmic reticulum (ER) stress with associated autophagy, and to enhance anti-tumor immunity in murine OSCC models by activating lymph node CD169⁺ macrophages and promoting cytotoxic T-cell infiltration. Evidence from other malignancies further implicates cell-cycle arrest, PI3K/Akt/mTOR, MAPK, NF-κB and STAT3 signalling, as well as suppression of invasion, EMT and angiogenesis, which are plausible but incompletely validated in oral cancer. Clinical translation is limited by poor aqueous solubility, extensive first-pass conjugation and low oral bioavailability. Local delivery systems such as mucoadhesive buccal films, nanocarriers and crystal-engineering approaches (e.g., cocrystals) may allow higher mucosal exposure at the lesion site. This review summarises current knowledge on the molecular targets and antiproliferative mechanisms of naringenin in oral cancer, discusses pharmacokinetic and formulation challenges, and outlines priorities for future research.



Keywords

naringenin; oral squamous cell carcinoma; flavanone; apoptosis; ROS; ER stress; autophagy; PI3K/Akt/mTOR; buccal drug delivery; chemoprevention



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References


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