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 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.
Yamamoto
D
D
Department of Pathology II, Kansai Medical University, Moriguchi, Osaka, Japan.
Kiyozuka
Y
Y
Adachi
Y
Y
Takada
H
H
Hioki
K
K
Tsubura
A
A
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003510:Cyclohexanes; D053938:DNA Fragmentation; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494826:BAX protein, human; C494811:BCL2L1 protein, human; D003510:Cyclohexanes; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012717:Sesquiterpenes; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D015118:Eicosapentaenoic Acid; D000077609:O-(Chloroacetylcarbamoyl)fumagillol