Synergistic Cytotoxicity From Combination of Lupeol and Ionizing Radiation in Head and Neck Cancer Cells

Ionizing radiation (IR) is one of the most conventional treatment regimens for treatment of Head and Neck Squamous Cell Carcinoma (HNSCC). It is often employed as a primary treatment or as an adjuvant to surgery. Despondently IR has its own drawbacks including radiation resistance, poor prognosis and frequent recurrence. The main objective of this work was to check the synergistic effect of Lupeol along with IR in order to observe if adjuvant treatment of novel phytochemicals like Lupeol with IR shows better efficacy. Head and Neck cancer cell line HEp-2 and UPCI: SCC 131 was treated with both Lupeol (50 µM) and IR (2 Gy) for short interval and the cytotoxicity of the drug combination was evaluated. Data showed synergistic effect of Lupeol with IR in both cell lines. The combination of lupeol and IR had highest cytotoxicity, induction of apoptosis was also found to be higher in the combination treatment. Additionally the combination also inhibited cell migration and sphere formation capability indicating direct effect of the combinatorial treatment on the Epithelial to Messenchymal transition (EMT) forming population of HNSCC cells. Findings also showed downregulation of key oncoproteins (AKT, NF-kB, COX-2) in the combination treatment proving synergistic effect of Lupeol with ionizing radiation in killing Head and Neck cancer cells by downregulating several oncogenic pathways.