Abstract
The aim of the present study was to investigate the anticancer effects and potential mechanisms of polyphenol epigallocatechin-3-gallate (EGCG) on breast cancer MCF-7 cells in vitro and in vivo. Our results showed that EGCG significantly inhibited MCF-7 cell viability in a time- and dose-dependent manner. Flow cytometry analysis indicated that EGCG induced apoptosis and disrupted cell cycle progression at G2/M phase. Moreover, EGCG inhibited miR-25 expression and increased PARP, pro-caspase-3 and pro-caspase-9 at protein levels. Restoration of miR-25 inhibited EGCG-induced cell apoptosis. Furthermore, EGCG suppressed tumor growth in vivo by downregulating the expression of miR-25 and proteins associated with apoptosis, which was further confirmed by a reduction of Ki-67 and increase of pro-apoptotic PARP expression as determined by immunohistochemistry staining. These findings indicate that EGCG possesses chemopreventive potential in breast cancer which may serve as a promising anticancer agent for clinical applications.
Keywords:
Polyphenol epigallocatechin-3-gallate; apoptosis; breast cancer; proliferation.
MeSH terms
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Animals
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Antineoplastic Agents, Phytogenic / pharmacology*
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Apoptosis / drug effects
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Apoptosis / genetics
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Caspase 3 / genetics
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Caspase 3 / metabolism
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Caspase 9 / genetics
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Caspase 9 / metabolism
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Catechin / analogs & derivatives*
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Catechin / pharmacology
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Cell Proliferation / drug effects*
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Female
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G2 Phase Cell Cycle Checkpoints / drug effects
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G2 Phase Cell Cycle Checkpoints / genetics
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Gene Expression Regulation, Neoplastic*
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Humans
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Ki-67 Antigen / genetics
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Ki-67 Antigen / metabolism
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MCF-7 Cells
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Mice
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Mice, SCID
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MicroRNAs / antagonists & inhibitors
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MicroRNAs / genetics*
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MicroRNAs / metabolism
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Poly(ADP-ribose) Polymerases / genetics
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Poly(ADP-ribose) Polymerases / metabolism
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Signal Transduction
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Tumor Burden / drug effects
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Xenograft Model Antitumor Assays
Substances
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Antineoplastic Agents, Phytogenic
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Ki-67 Antigen
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MIRN25 microRNA, human
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MicroRNAs
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Catechin
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epigallocatechin gallate
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Poly(ADP-ribose) Polymerases
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Caspase 3
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Caspase 9