Abstract A004: Chemoprevention of head and neck cancers by the combination of epigallocatechin gallate (EGCG) and resveratrol

Abstract

Abstract Head and neck cancer (HNC) is a devastating disease and the 6th most common cancer worldwide. Most HNC patients are diagnosed with advanced stage disease for which the 5-year survival is below 50%, stressing the need for chemoprevention. Recently, we have reported that the combination of resveratrol and EGCG induces synergistic apoptosis and inhibits xenografted HNC growth by inhibiting AKT-mTOR pathway. In this study, we have investigated the chemopreventive efficacy of resveratrol, EGCG and their combination using 4NQO-induced oral carcinogenesis model. C57BL/6 mice were exposed to 4-NQO (50 μg/ml) via drinking water for 10 weeks, followed by treatment with vehicle (50% sweetened condense milk), resveratrol (30 mg/kg), EGCG (30 mg/kg) and their combination for 8 weeks, 5 days/week. The mice were sacrificed on week 24 and the number of visible and microscopic lesions were counted. Resveratrol alone and in combination with EGCG significantly inhibited the number of visible lesions whereas the number of microscopic lesions and lesion area were significantly inhibited only in the combination group. Furthermore, RNASeq and qPCR analysis using a HNC cell line identified GDF15, ATF3, p21, p27 and Bim as significantly upregulated genes with GDF15 being the most upregulated one. Expression of GDF15 and ATF3 proteins were confirmed by western blotting. Taken together, our data strongly demonstrate the chemopreventive potential of the combination of EGCG and resveratrol and paves the way for further clinical developments. (Supported by NIH Grant P20GM103434 to the West Virginia IDeA Network for Biomedical Research Excellence) Citation Format: Adeoluwa Adeluola, Lukmon Raji, Saroj Sigdel, A.S.M. Anisuzzaman, A. R. M. Ruhul Amin. Chemoprevention of head and neck cancers by the combination of epigallocatechin gallate (EGCG) and resveratrol [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A004.