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Specific Inhibition of Hypoxia-inducible Factor (HIF)-1.ALPHA. Activation and of Vascular Endothelial Growth Factor (VEGF) Production by Flavonoids
- Source :
- Biological and Pharmaceutical Bulletin. 26:1379-1383
- Publication Year :
- 2003
- Publisher :
- Pharmaceutical Society of Japan, 2003.
-
Abstract
- Screening using a reporter under the control of the hypoxia-response element (HRE) identified several flavonoids and homoisoflavonoids that inhibit the activation of HRE under hypoxic conditions. Among various compounds, isorhamnetin, luteolin, quercetin, and methyl ophiopogonanone B (MOB) were effective at 3 to 9 microg/ml in inhibiting the reporter activity. The expression of vascular endothelial growth factor (VEGF) mRNA during hypoxia was also inhibited by MOB in HepG2 cells, but the effective doses were 10 to 20 microg/ml. MOB caused destabilization of hypoxia-inducible factor (HIF)-1alpha, as revealed by Western blotting, that was dependent on proteasome activity and the tumor suppressor, p53. The tubular formation and migration of human umbilical vein endothelial cells was also inhibited by MOB. MOB is expected to act as an inhibitor of angiogenesis.
- Subjects :
- Vascular Endothelial Growth Factor A
medicine.medical_specialty
Angiogenesis
Pharmaceutical Science
CHO Cells
Biology
Umbilical vein
Cell Line
chemistry.chemical_compound
Cricetinae
Internal medicine
medicine
Animals
Humans
RNA, Messenger
Cells, Cultured
Flavonoids
Pharmacology
Reporter gene
General Medicine
Hypoxia-Inducible Factor 1, alpha Subunit
Molecular biology
Cell Hypoxia
Vascular endothelial growth factor
Blot
Endocrinology
Gene Expression Regulation
chemistry
Hypoxia-inducible factors
Cell culture
Luteolin
HeLa Cells
Transcription Factors
Subjects
Details
- ISSN :
- 13475215 and 09186158
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Biological and Pharmaceutical Bulletin
- Accession number :
- edsair.doi.dedup.....ee9f7f7f3f7a60b70fb32390c5ab6f56