Background: The Indian subcontinent has the highest incidence and prevalence of Oral Squamous cell carcinoma. Recently, there has been a shift in paradigm favoring natural products to combat cancer, owing to the high costs and immense side effects associated with the conventional treatments such as surgery, radiotherapy, and chemotherapy. Cancer statistics express that consumption of diets rich in fresh fruits and vegetables is inversely associated with cancer incidence. The same has led to the increased number of studies in this area in recent times. The cytotoxic effect of many fruit extracts on various cancers, like cervical cancer, breast cancer, and colon cancer, has been reported. 

Aim: To evaluate the cytotoxic effect of Vaccinium macrocarpon (cranberry) and Punica granatum (pomegranate) extracts on oral cancer cell lines. 

Materials and Methods: Ethanolic extract of Punica granatum pericarp, fruit, and Vaccinium macrocarpon fruit were prepared. Oral cancer (KB) cell line was procured and cultured. Anti- proliferative assay (MTT assay) was performed with various concentrations of all three fruit extracts on oral cancer. Percentage of cell viability for each concentration was calculated, and the half maximal inhibitory concentration (IC50) was derived for the extracts. The role of apoptosis in the cytotoxicity of these extracts was assessed by analysing DNA fragmentation via gel electrophoresis. The data obtained was analysed using Pearson's correlation. 

Results: The study revealed a significant decrease in the percentage of viable cells with increasing concentration of the extract. The IC50 value of Punica granatum pericarp, fruit, and Vaccinium macrocarpon extract was 5.625 mu g/mL, 15 mu g/mL, and 27.5 mu g/mL, respectively. On comparison, Punica granatum pericarp extract showed the highest anti-carcinogenic activity. The DNA fragmentation assay showed a DNA laddering pattern, indicative of apoptosis, in the cells treated with Punica granatum pericarp extract. 

Conclusion: Punic granatum pericarp, fruit, and Vaccinium macrocarpon exhibited sufficient anticancer activity against oral cancer (KB) cells. Apoptosis was shown to play a role in the cytotoxic effect of Punica granatum pericarp extract against oral cancer cells.