Abstract
The effects of eicosapentaenoic acid (EPA) and an angiogenesis inhibitor (TNP-470) on the suppression of breast cancer cell growth were examined in five human breast cancer cell lines (MDA-MB-231, T-47D, MCF-7, KPL-1, and MKL-F). In all five cell lines, EPA and TNP-470 alone both showed tumor growth inhibition in a time- and dose-dependent manner, and in combination, a synergistic effect was seen at high concentrations. EPA plus TNP-470 treatment evoked apoptosis as confirmed by the appearance of sub G1 populations, by DNA fragmentation, and by cell morphology. With the combination, the expression of Bax and Bcl-xS, the apoptosis-enhancing proteins, was more up-regulated and that of Bcl-2 and Bcl-xL, the apoptosis-suppressing proteins, was more down-regulated compared to the use of EPA or TNP-470 alone, suggesting that their synergistic effect was due to an acceleration of apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects*
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Apoptosis / genetics
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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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Cyclohexanes
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DNA Fragmentation
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Drug Screening Assays, Antitumor
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Drug Synergism
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Eicosapentaenoic Acid / pharmacology*
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Female
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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O-(Chloroacetylcarbamoyl)fumagillol
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Sesquiterpenes / pharmacology*
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Signal Transduction / drug effects
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Tumor Cells, Cultured / drug effects
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bcl-2-Associated X Protein
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bcl-X Protein
Substances
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BAX protein, human
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BCL2L1 protein, human
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Cyclohexanes
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Neoplasm Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Sesquiterpenes
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bcl-2-Associated X Protein
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bcl-X Protein
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Eicosapentaenoic Acid
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O-(Chloroacetylcarbamoyl)fumagillol