Abstract 3667: Pro-oxidant effects of the green tea catechin, (-)-epigallocatechin-3-gallate in oral cancer cells: A role for the mitochondria.

Abstract

Abstract (-)-Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea (Camellia sinensis). Many laboratory studies have demonstrated its potential cancer chemopreventive effects. Previously, we found that EGCG inhibited cell growth and induced apoptosis in oral squamous carcinoma cells (SCC-25 and SCC-9), and that, EGCG-induced intracellular ROS played a key role in the inhibitory effects. EGCG treatment also caused a significant loss of mitochondrial membrane potential after 72 h, suggesting that mitochondrial dysfunction may have caused the increased intracellular ROS. In the present study, we further explored the role of the mitochondria in EGCG-mediated oxidative stress. We found that EGCG-induced intracellular ROS initially co-localized with the mitochondria of SCC-25 cells (by 1 h) and then spread throughout the cell. Treatment with 100 μM EGCG for 24 h inhibited the activity of mitochondrial membrane complex I by 50% and tended to inhibit complex III. These results demonstrate that EGCG can induce mitochondrial dysfunction in part by impairing electron transfer chain, resulting in increased intracellular ROS. Using qPCR, we found time-dependent changes in several genes. The expressions of thyroid peroxidase (TPO, 2.9-fold), Bcl2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3, 2.2-fold) and glutathione peroxidase 2 (GPX2, 1.2-fold) were increased within 6 h treatment. The latter two genes are related to mitochondrial dysfunction and oxidative stress, respectively. By contrast to cancer cells, EGCG did not induce significant cell growth inhibition and apoptosis in normal human gingival fibroblast cells (HGF-1). EGCG treatment actually reduced intracellular ROS in HGF-1 cells in contrast to the increase observed in the cancer cell lines, indicating selective pro-oxidant effects of EGCG in oral cancer cells. In conclusion, induction of mitochondrial dysfunction and resultant production of intracellular ROS appear to play a significant role in the inhibitory effects of EGCG against oral cancer cells. The differential responses of cancer cells and normal cells to EGCG are being further studied. Citation Format: Ling Tao, Sarah C. Forester, Joshua D. Lambert. Pro-oxidant effects of the green tea catechin, (-)-epigallocatechin-3-gallate in oral cancer cells: A role for the mitochondria. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3667. doi:10.1158/1538-7445.AM2013-3667