HSP70와 HSP90의 억제를 통한 Epigallocatechin-3-gallate의 종양 성장 억제효과

Abstract

Epigallocatechin-3-gallate (EGCG), a catechin found in green tea, has been recognized as a potential therapeutic agent against human cancer. However, mechanism of cytotoxic effect of EGCG on cancer cells has been still unclear. In this study, we assessed the ability of EGCG to regulation of heat shock response signaling in the breast carcinoma cell. EGCG inhibited cell growth in a dose dependent manner and specifically suppressed the expression of HSP70 and HSP90 but other HSPs were not affected. We also found that EGCG inhibited the transcriptional activity of HSP70 and HSP90 promoter through blocking of HSF1 and HSF2. Interestingly, pretreatment of EGCG (50 or 100 μM) in cells synergistically decreased the cell viability by heat shock (44 oC for 1 h) or oxidative stress (H2O2, 500 μM for 24 h) compared with untreated cell. In xenograft mouse model, treatment of EGCG (10 mg/kg) also significantly reduce the tumor size through inhibiting the expression of HSP70 and HSP90. Our findings suggested that EGCG was a potent tumor suppressor that targeted HSP70 and HSP90 expression in breast cancer cells.