Curcumin induces down-regulation of EZH2 expression through the MAPK pathway in MDA-MB-435 human breast cancer cells

被引:91
作者
Hua, Wen-Feng [1 ]
Fu, Yong-Shui [1 ,2 ]
Liao, Yi-Ji [1 ]
Xia, Wen-Jie [2 ]
Chen, Yang-Chao [3 ]
Zeng, Yi-Xin [1 ]
Kung, Hsiang-Fu [1 ,3 ]
Xie, Dan [1 ]
机构
[1] Sun Yat Sen Univ, State Key Lab Oncol S China, Ctr Canc, Guangzhou 510060, Guangdong, Peoples R China
[2] Guangzhou Blood Ctr, Guangzhou 510095, Guangdong, Peoples R China
[3] Chinese Univ Hong Kong, State Key Lab Oncol S China, Hong Kong, Hong Kong, Peoples R China
关键词
Curcumin; EZH2; MAPK; Histone methyltransferase; Breast cancer; ZESTE HOMOLOG-2; PROTEIN; PROLIFERATION; INHIBITORS; APOPTOSIS; ACETYLTRANSFERASE; TRANSCRIPTION; METHYLATION; CARCINOMA; INVASION;
D O I
10.1016/j.ejphar.2010.03.051
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Curcumin, a natural compound isolated from turmeric, may inhibit cell proliferation in various tumor cells through a mechanism that is not fully understood. The enhancer of zeste homolog 2 (EZH2) gene is overexpressed in human breast cancers with poor prognosis. In this study, we observed a dose- and time-dependent down-regulation of expression of EZH2 by curcumin that correlates with decreased proliferation in the MDA-MB-435 breast cancer cell line. The curcumin treatment resulted in an accumulation of cells in the G(1) phase of the cell cycle. Further investigation revealed that curcumin-induced down-regulation of EZH2 through stimulation of three major members of the mitogen-activated protein kinase (MAPK) pathway: c-Jun NH2-terminal kinase (INK), extracellular signal-regulated kinase (ERK) and p38 kinase. These data suggest that an underlying mechanism of the MAPK pathway mediates the down-regulation of EZH2, thus contributing to the anti-proliferative effects of curcumin against breast cancer. (C) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:16 / 21
页数:6
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