Myricetin inhibits UVB-induced angiogenesis by regulating PI-3 kinase in vivo

Myricetin is one of the principal phytochemicals in onions, berries and red wine. Previous studies showed that myricetin exhibits potent anticancer and chemopreventive effects. The present study examined the effect of myricetin on ultraviolet (UV) B-induced angiogenesis in an SKH-1 hairless mouse sk...

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Bibliographic Details
Published in:Carcinogenesis (New York) 2010-05, Vol.31 (5), p.911-917
Main Authors: Jung, Sung Keun, Lee, Ki Won, Byun, Sanguine, Lee, Eun Jung, Kim, Jong-Eun, Bode, Ann M., Dong, Zigang, Lee, Hyong Joo
Format: Article
Language:English
Subjects:
AKT protein
Allium cepa
Angiogenesis Inhibitors - pharmacology
Animals
Biological and medical sciences
Carcinogenesis
Carcinogenesis, carcinogens and anticarcinogens
Extracellular Signal-Regulated MAP Kinases - metabolism
Flavonoids - pharmacology
Hypoxia-Inducible Factor 1, alpha Subunit - analysis
Matrix Metalloproteinase 13 - analysis
Matrix Metalloproteinase 9 - analysis
Medical sciences
Mice
Mice, Hairless
Neovascularization, Pathologic - prevention & control
Phosphatidylinositol 3-Kinases - metabolism
Phosphorylation
Proto-Oncogene Proteins c-akt - metabolism
Ribosomal Protein S6 Kinases, 70-kDa - metabolism
Tumors
Ultraviolet Rays
Vascular Endothelial Growth Factor A - analysis
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Summary:Myricetin is one of the principal phytochemicals in onions, berries and red wine. Previous studies showed that myricetin exhibits potent anticancer and chemopreventive effects. The present study examined the effect of myricetin on ultraviolet (UV) B-induced angiogenesis in an SKH-1 hairless mouse skin tumorigenesis model. Topical treatment with myricetin inhibited repetitive UVB-induced neovascularization in SKH-1 hairless mouse skin. The induction of vascular endothelial growth factor, matrix metalloproteinase (MMP)-9 and MMP-13 expression by chronic UVB irradiation was significantly suppressed by myricetin treatment. Immunohistochemical and western blot analyses revealed that myricetin inhibited UVB-induced hypoxia inducible factor-1α expression in mouse skin. Western blot analysis and kinase assay data revealed that myricetin suppressed UVB-induced phosphatidylinositol-3 (PI-3) kinase activity and subsequently attenuated the UVB-induced phosphorylation of Akt/p70S6K in mouse skin lysates. A pull-down assay revealed the direct binding of PI-3 kinase and myricetin in mouse skin lysates. Our results indicate that myricetin suppresses UVB-induced angiogenesis by regulating PI-3 kinase activity in vivo in mouse skin.
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/bgp221