Abstract 6062: Radiosensitizing head and neck squamous cell carcinoma using isothiocyanates

Abstract

Abstract Head and neck cancer kills over 400,000 people each year with the majority of cases being head and neck squamous cell carcinoma (HNSCC). Despite major advances in cancer treatment, radiation resistance contributes to increased morbidity and mortality of patients with HNSCC. Few FDA-approved radiosensitizers exist for the treatment of HNSCC and the majority are associated with severe adverse effects. Therefore, there is a clear need to examine novel treatment combinations to improve radiosensitivity and HNSCC outcomes. Isothiocyanates enhance response to cytokines, chemotherapy, and radiation in other in vitro and in vivo cancer models, including pancreatic and breast cancer. Isothiocyanates are antioxidants found in cruciferous vegetables such as watercress and broccoli. Phenethyl isothiocyanate (PEITC) was well tolerated by patients in chemopreventative clinical trials and was thus selected for this study. We hypothesize that PEITC radiosensitizes HNSCC cells through increasing DNA damage, apoptosis and reactive oxygen species (ROS). Non-human papilloma virus or P16 negative HNSCC are associated with increased radioresistance and as such human HNSCC cell lines HN5 and CAL27 were selected. Combination of PEITC and photon radiation (XRT) decreased cell survival by half as compared to cells treated with PEITC or XRT alone for both HN5 and CAL27 cells as determined by clonogenic assay (n≥3). PEITC enhanced XRT-induced apoptosis in HN5 and CAL27 cells as indicated by increased cleavage of effector caspases 3 and 7, which was reversed upon treatment with pan-caspase inhibitor, QVD-OPH. Preliminary comet assays identified that combination of PEITC with XRT significantly increased Tail DNA % relative to vehicle (p<0.001), PEITC alone (p<0.0001), or XRT alone (p<0.0001) in HN5 cells. Preliminary data in CAL27 cells identified significantly increased signal of y-H2Ax in cells treated with both PEITC and XRT was 2.2 fold higher than XRT alone (p<0.001) and 12.1 fold higher than PEITC alone (p<0.001) in CAL27 cells. PEITC increased XRT-induced ROS generation in CAL27 cells relative to independent treatment as determined by 2′,7′ dichlorodihydrofluorescein diacetate (DCFH-DA) staining. Taken together, these results support that PEITC synergistically enhances HNSCC cell response to XRT. The results of this study warrant further investigation into the potential of PEITC to improve radiation efficacy in pre-clinical HNSCC models with the long-term goal of testing this well-tolerated compound in clinical trials. Citation Format: Christina Ann Wicker, Samuel Thompson, Poornima Dubey, Vinita Takiar. Radiosensitizing head and neck squamous cell carcinoma using isothiocyanates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6062.