The potential and promise of natural antioxidants as epigenetic modulators in oral squamous cell carcinoma.

Oral squamous cell carcinoma is the most common oral malignancy and poses a major health challenge because of late-stage diagnosis, high recurrence, and resistance to treatment. In addition to genetic mutations, oral squamous cell carcinoma is strongly influenced by epigenetic alterations, including abnormal DNA methylation, histone modifications, and dysregulated non-coding RNAs. These changes contribute to the inhibition of tumor suppressor genes and regulation of oncogenic pathways, which promote cancer progression. Oxidative stress and excessive reactive oxygen species further drive these epigenetic changes, creating a vicious cycle that fuels carcinogenesis. Natural antioxidants, including genistein, epigallocatechin gallate, resveratrol, lycopene, and quercetin, have shown promise in preventing and treating oral squamous cell carcinoma. Their multi-targeted actions involve the inhibition of DNA methyltransferases, reversal of tumor suppressor gene promoter hypermethylation, regulation of histone acetylation and methylation, and regulation of microRNAs (miRNAs) that suppress oncogene activity. These compounds restore normal gene function with low toxicity to healthy cells, making them appealing candidates for personalized therapy. By targeting both oxidative stress and epigenetic instability, natural antioxidants offer a promising strategy against the core mechanisms of oral squamous cell carcinoma. Understanding this molecular interplay may employ more effective prevention and therapeutic approaches in future oral squamous cell carcinoma management paradigms.