Integrative Role of Natural Bio-actives in Oral Cancer Therapy: Mechanisms of Protection and Efficacy

Abstract

Oral cancer, particularly oral squamous cell carcinoma (OSCC), remains a significant global health burden with high morbidity and mortality rates, largely due to late diagnosis and the cytotoxic side effects of conventional therapies. While chemotherapeutic agents remain central to oral cancer management, their lack of selectivity often damages healthy oral tissues, leading to adverse outcomes such as mucositis, xerostomia, myelosuppression, and systemic inflammation, apoptosis, and autophagy. Notably, agents such as curcumin, thymoquinone, resveratrol, quercetin and betanin have been shown to activate Nrf2/ARE antioxidant defences, inhibit NF-κB driven inflammation, preserve mitochondria membrane potential, and regulate apoptotic pathways selectively in cancer versus normal cells. Moreover, their influence on P13K/Akt/mTOR signalling, p53 modulation, and epigenic reprogramming further underscores their therapeutic relevance. This review critically examines the integrative role of bioactive compounds in enhancing treatment efficacy, minimizing off target toxicities, and supporting oral tissue homeostasis offering a framework for incorporating phytochemicals into multimodal oral cancer therapies.