Elucidating the potential of phytochemicals in targeting various signalling pathways of oral cancer: Current update on their clinical translational potential

Oral cancer is a global health concern, which has strong connection with various etiological factors which include tobacco, alcohol, betel quid use, human papillomavirus infection, and genetic/epigenetic alterations. Current treatment approaches, including surgery, radiotherapy, and chemotherapy, often suffer various draw backs due to limited efficacy and resistance, underscoring the need for safer, more effective alternatives. Novel phytochemical such as curcumin, resveratrol, epigallocatechin gallate, isothiocyanates, and lycopene have emerged as promising candidates for the management of oral squamous cell carcinoma due to their multitargeted molecular actions and low toxicity. Lycopene, a carotenoid present abundantly in tomatoes,which has been proven to inhibit epithelial–mesenchymal transition (EMT) and induce apoptosis in Oral Squamoous cell carcinoma via suppression of the PI3K/AKT/mTOR pathway, while also upregulating the E-cadherin expression and reducing the oxidative DNA damage. Similarly, isothiocyanates such as sulforaphane, phenethyl isothiocyanate) which modulate the activities of p53, Bax/Bcl-2, caspases and histone deacetylases activity which lead to apoptosis, cell cycle arrest, and inhibition of metastasis. These compounds also influence critical pathways mainly NF-κB, MAPK, and Wnt/β-catenin, thereby decereasing the proliferation, angiogenesis, and invasion of cancer.Although the promising results in various preclinical studies various challenges include poor solubility, low bioavailability, and limited targeted delivery systems downregulate their therapeutic potential.