Abstract A178: Epigallocatechin-3-gallate (EGCG) induces catalase-sensitive cell growth inhibition and AKT activation in Burkitt lymphoma cells.

Abstract

Abstract Burkitt lymphoma is an aggressive non-Hodgkin's B cell lymphoma. It is typically treated with high intensity chemotherapy, which is associated with toxicities. Therefore, it is important to develop novel treatments for this disease. Studies have found that the green tea-derived compound, epigallocatechin-3-gallate (EGCG), may be effective in treating Burkitt lymphoma (Nakazato T. et. al., 2005 and Noda C. et. al., 2007). Another study showed that the phosphatidylinositide 3-kinase (PI3K)/AKT pathway is important for Burkitt lymphoma proliferation and survival (Schmizt R. et. al., 2012). Therefore the purpose of this current study is to investigate the connection between EGCG and the PI3K/AKT pathway in Burkitt lymphoma cells. To begin, it was evaluated whether EGCG would induce dose-dependent, catalase-sensitive growth inhibition of the sporadic Burkitt lymphoma cell lines, BL41-3, DG75, and Ramos. These cells were treated with EGCG at varying doses and also in the presence or absence of catalase followed by MTT analysis. EGCG induced a dose-dependent growth inhibition of all three Burkitt lymphoma cell lines and co-treatment with catalase prevented this effect. To determine the effects of EGCG on the PI3K/AKT pathway, BL41-3, DG75, and Ramos, were treated with 0, 20, 40, or 80 μM EGCG followed by Western analysis for phosphorylated AKT and total AKT. The results indicated that AKT phosphorylation is increased in all three cell lines following EGCG treatment. Lastly, it was investigated how inhibition of PI3K during EGCG treatment impacts the anti-proliferative effects seen with EGCG alone. To test this, BL41-3, DG75, and Ramos cells were treated with EGCG and an inhibitor of PI3K, LY294002, followed by MTT analysis. EGCG and LY294002 inhibited Burkitt lymphoma cell growth, although the degree of inhibition and the effect of combination treatment varied between the three cell lines. In conclusion, EGCG induced AKT phosphorylation along with a catalase-sensitive growth inhibition and the addition of a PI3K inhibitor had an additive growth inhibitory effect with EGCG. These results provide novel insight into the use of EGCG for the treatment of sporadic Burkitt lymphomas. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A178. Citation Format: Carl-Christian Van Doorn, Aaron M. Domina. Epigallocatechin-3-gallate (EGCG) induces catalase-sensitive cell growth inhibition and AKT activation in Burkitt lymphoma cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A178.