Authors: Mi Hee Lee DongWook Han SuongHyu Hyon JongChul Park
Publish Date: 2010/10/21
Volume: 16, Issue: 1, Pages: 75-85
Abstract
Animal tumor bioassays and in vitro cell culture systems have demonstrated that epigallocatechin3Ogallate EGCG the predominant catechin in green tea possesses antiproliferative and proapoptotic effects on various cancer cells and tumors In this study we investigated the effects of EGCG on cell growth cell cycle progression and apoptosis in human fibrosarcoma HT1080 cells The involvement of p53 Bcl2 Bax caspases and nuclear factorκB NFκB was examined as a mechanism for the anticancer activity of EGCG Timedependent intracellular trafficking of EGCG was also determined using fluorescein isothiocyanate FITCconjugated EGCG FITCEGCG Our data show that EGCG treatment caused dosedependent cell growth inhibition cell cycle arrest at the G0/G1 phase and DNA fragmentation suggesting the induction of apoptosis in HT1080 cells Immunoblot analysis revealed that the expression of p53 caspase7 and 9 as well as the ratio of Bax/Bcl2 protein increased significantly with higher EGCG concentrations and longer incubation times Moreover expression of phosphorylated NFκB/p65 in HT1080 cells was inhibited by EGCG treatment in a dosedependent manner while that of unphosphorylated NFκB/p65 remained unaffected Here we also reveal timedependent internalization of FITCEGCG into the cytosol of HT1080 cells and its subsequent nuclear translocation These results suggest that EGCG may interrupt exogenous signals directed towards genes involved in proliferation and cell cycle progression Taken together our data indicate that HT1080 apoptosis may be mediated through the induction of p53 and caspases by the prooxidant activity of internalized EGCG as well as suppression of Bcl2 and phosphorylated NFκB by the antioxidant activity of EGCGThis research was partly supported by the Korea Healthcare Technology RD Project Ministry for Health Welfare Family Affairs Republic of Korea A085136 and by a grant from the Fundamental RD Program for Core Technology of Materials funded by the Ministry of Knowledge Economy Republic of Korea K0006028
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