Abstract
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 (JNK), 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.
Copyright 2010 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Breast Neoplasms / enzymology
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Curcumin / pharmacology*
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DNA-Binding Proteins / biosynthesis*
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DNA-Binding Proteins / genetics
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Down-Regulation / drug effects*
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Enhancer of Zeste Homolog 2 Protein
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Female
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Gene Expression Regulation, Neoplastic / drug effects*
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Humans
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JNK Mitogen-Activated Protein Kinases / metabolism
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MAP Kinase Signaling System / drug effects*
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Polycomb Repressive Complex 2
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Transcription Factors / biosynthesis*
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Transcription Factors / genetics
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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DNA-Binding Proteins
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Transcription Factors
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EZH2 protein, human
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Enhancer of Zeste Homolog 2 Protein
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Polycomb Repressive Complex 2
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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Curcumin