Premium
Mechanistic study for non‐oxidative anticancer activity of epigallocatechin‐3‐gallate in MCF‐7 human breast cancer cells (644.6)
Author(s) -
Ono Misaki,
Takeshima Mikako,
Higuchi Takako,
Chen Chen,
Nakano Shuji
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.644.6
Subject(s) - apoptosis , oxidative stress , protein kinase b , cytotoxicity , catalase , chemistry , pi3k/akt/mtor pathway , mcf 7 , mapk/erk pathway , cancer cell , cancer research , pharmacology , signal transduction , biology , biochemistry , cancer , in vitro , human breast , genetics
Despite its strong antioxidant activity, epigallocatechin‐3‐gallate (EGCG), a green tea polyphenol, induces growth inhibition and apoptosis in many human tumor cells through oxidative stress by producing H 2 O 2 . Because these cellular events were reversed by exogenous catalase, H 2 O 2 has been considered as the main cause of the cytotoxicity of EGCG. However, its cytotoxicity was not fully reversed by catalase. We investigated such non‐oxidative anticancer mechanisms of EGCG using MCF‐7 human breast cancer cells. EGCG showed dose‐dependent cytotoxicity, with pronounced membrane alterations characterized by bleb. Co‐treatment with catalase drastically reduced the cytotoxicity from 95% to 48%. To determine non‐oxidative anticancer activity of EGCG, cells were treated with 50 µM EGCG in the presence of catalase, and cell cycle progression and signaling proteins for growth and apoptosis were assessed. EGCG arrested cells in G1/S phase and increased apoptotic cell population. Upon treatment with EGCG, Erk and Akt were inactivated with subsequent reductions of activities of downstream mTOR and S6K1. Anti‐apoptotic Bcl‐2 was reduced while pro‐apoptotic Bax increased. These results suggest that non‐oxidative anticancer activities of EGCG were mediated by G1/S arrest and apoptosis through ablation of signal transduction involving Erk, Akt, mTOR pathways as well as suppression of Bcl‐2 and enhancement of Bax.