Abstract
Deacetyl-mycoepoxydiene (DM), a novel secondary metabolite produced by the plant endophytic fungi Phomosis sp., induced the reorganization of cytoskeleton in actively growing MCF-7 cells by promoting polymerization of tubulin. DM could induce cell cycle arrest at G2/M in MCF-7 cells. Additionally, DM-induced apoptosis was characterized with up-regulating caspase-3, Bax, caspase-9, parp, and p21 while down-regulating Bcl-2 activation. DM conferred dose- and time-dependent inhibitory effects upon cell proliferation of MCF-7 cells both in cultured cells and nude mice with human breast carcinoma xenografts. The results obtained from these in vitro and in vivo models provide new data revealing the potential for DM as a novel microtubule inhibitor.
Keywords:
Apoptosis; Cell cycle arrest; Microtubule inhibitor.
Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bridged Bicyclo Compounds, Heterocyclic / chemistry
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Bridged Bicyclo Compounds, Heterocyclic / isolation & purification*
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
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Bridged-Ring Compounds / chemistry
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Bridged-Ring Compounds / isolation & purification*
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Bridged-Ring Compounds / pharmacology*
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Cell Cycle Checkpoints / drug effects
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Cell Death / drug effects
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Cell Division / drug effects
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Endophytes / chemistry*
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Female
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Fungi / chemistry*
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G2 Phase / drug effects
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Humans
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MCF-7 Cells
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Mice, Inbred BALB C
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Mice, Nude
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Microtubules / drug effects*
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Microtubules / metabolism
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Polymerization
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Pyrones / chemistry
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Pyrones / isolation & purification*
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Pyrones / pharmacology*
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Xenograft Model Antitumor Assays
Substances
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Bridged Bicyclo Compounds, Heterocyclic
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Bridged-Ring Compounds
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Pyrones
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deacetyl-mycoepoxydiene
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mycoepoxydiene