Abstract 5436: The role of reactive oxygen species in (-)-epigallocatechin-3-gallate (EGCG)-induced cell growth inhibition and apoptosis in oral cancer cells

(-)-Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea (Camellia sinensis L.). Recently, it has been reported to have cancer chemotherapeutic and chemopreventive effects. However, the mechanisms are incompletely understood. We found that EGCG induced both extracellular and intracellular reactive oxygen species (ROS) in SCC-25 and SCC-9 human oral squamous carcinoma cells. Extracellular ROS was produced rapidly in the DMEM/F12 (1:1) cell culture medium, but was also quenched very rapidly (t_1/2 = 1.7 h). By contrast, the level of intracellular ROS increased more slowly and was increasing even after EGCG could no longer be detected in either the cytosol or the cell culture medium. We observed that EGCG treatment decreased the mitochondrial membrane potential suggesting that EGCG induced dysfunction of electron transport chain in the mitochondria of treated cells. This may explain the continuous ROS production in the cells even after EGCG levels have dropped to below the limit of detection. EGCG treatment for 72 hr reduced cell viability significantly (IC₅₀=127 µM in SCC-25 cells and IC₅₀=83 µM in SCC-9 cells). Effects on cell viability were modulated by inclusion of N-acetylcysteine, a thiol-antioxidant, indicating a role for EGCG-induced ROS in the reduction of cell viability. EGCG treatment also arrested cell cycle progression in the G2/M phase of cell cycle, and induced apoptosis (increased TUNEL positivity and annexin V staining). Based on the present studies, it appears that EGCG-induced oxidative stress and mitochondrial dysfunction play a role in its anti-oral cancer effects in cell culture. Ongoing studies in our laboratory are focused on the mechanism by which EGCG induces mitochondrial dysfunction, and the relevance of this mechanism to oral cancer prevention in vivo.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5436. doi:1538-7445.AM2012-5436