Anthracyclines, Small-Molecule Inhibitors of Hypoxia-Inducible Factor-1 Alpha Activation
| العنوان: | Anthracyclines, Small-Molecule Inhibitors of Hypoxia-Inducible Factor-1 Alpha Activation |
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| المؤلفون: | Kiyoshi Egawa, Setsuko Kunimoto, Yuki Hasebe, Yohko Yamazaki, Daishiro Ikeda, Kiyoshi Nose |
| المصدر: | Biological and Pharmaceutical Bulletin. 29:1999-2003 |
| بيانات النشر: | Pharmaceutical Society of Japan, 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Vascular Endothelial Growth Factor A, Pharmacology, Anthracycline, Daunorubicin, Angiogenesis, Pharmaceutical Science, CHO Cells, General Medicine, Biology, Hypoxia-Inducible Factor 1, alpha Subunit, Molecular biology, Vascular endothelial growth factor, chemistry.chemical_compound, Hypoxia-Inducible Factor 1-Alpha, Mediator, chemistry, Cricetinae, medicine, Animals, Anthracyclines, Doxorubicin, RNA, Messenger, Promoter Regions, Genetic, medicine.drug, Aclarubicin |
| الوصف: | Hypoxia-inducible factor-1 (HIF-1) is a central mediator of cellular responses to low oxygen and has recently become an important therapeutic target for solid tumor therapy. To identify small molecule inhibitors of the HIF-1 transcriptional activation, we have established a high through-put assay system using a stable transformant of mammalian cells that express the luciferase reporter gene construct containing a HIF-1 binding site. Using this system, we screened 5000 cultured broths of microorganisms, and we found that cinerubin (1-hydroxy aclacinomycin B) showed a significant inhibition of the reporter activity induced by hypoxic conditions. In addition, we demonstrated that aclarubicin also inhibited the HIF-1 transcriptional activity under hypoxic conditions, but neither doxorubicin nor daunorubicin inhibited it. Consistent with these results, cinerubin and aclarubicin inhibited the hypoxic induction of the vascular endothelial growth factor (VEGF) protein in HepG2 cells, but neither doxorubicin nor daunorubicin affected it. Thus, our results suggested that some anthracyclines are also acting as angiogenesis inhibitors. |
| تدمد: | 1347-5215 0918-6158 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d2f8c486e92a7d2eae0ab5c1d01ef23b https://doi.org/10.1248/bpb.29.1999 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d2f8c486e92a7d2eae0ab5c1d01ef23b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13475215 09186158 |
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