Synergistic action of apoptosis induced by eicosapentaenoic acid and TNP-470 on human breast cancer cells

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...

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Bibliographic Details
Published in:Breast cancer research and treatment 1999-05, Vol.55 (2), p.149-160
Main Authors: YAMAMOTO, D, KIYOZUKA, Y, ADACHI, Y, TAKADA, H, HIOKI, K, TSUBURA, A
Format: Article
Language:English
Subjects:
Antineoplastic agents
Apoptosis - drug effects
Apoptosis - genetics
bcl-2-Associated X Protein
bcl-X Protein
Biological and medical sciences
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cancer research
Cancer therapies
Chemotherapy
Cyclohexanes
DNA Fragmentation
Drug Screening Assays, Antitumor
Drug Synergism
Eicosapentaenoic Acid - pharmacology
Female
Gene Expression Regulation, Neoplastic - drug effects
Humans
Medical sciences
Neoplasm Proteins - biosynthesis
Neoplasm Proteins - genetics
O-(Chloroacetylcarbamoyl)fumagillol
Pharmacology. Drug treatments
Proto-Oncogene Proteins - biosynthesis
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-bcl-2 - biosynthesis
Proto-Oncogene Proteins c-bcl-2 - genetics
Sesquiterpenes - pharmacology
Signal Transduction - drug effects
Tumor Cells, Cultured - drug effects
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Summary: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.
ISSN:0167-6806
1573-7217
DOI:10.1023/a:1006283131240