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 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-1alpha 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/p70(S6K) 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.
Jung
Sung Keun
SK
Department of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Republic of Korea.
Lee
Ki Won
KW
Byun
Sanguine
S
Lee
Eun Jung
EJ
Kim
Jong-Eun
JE
Bode
Ann M
AM
Dong
Zigang
Z
Lee
Hyong Joo
HJ
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D053509:Matrix Metalloproteinase 13 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D051379:Mice; D008812:Mice, Hairless; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D014466:Ultraviolet Rays; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D020533:Angiogenesis Inhibitors; D005419:Flavonoids; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; C040015:myricetin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D048049:Extracellular Signal-Regulated MAP Kinases; D053509:Matrix Metalloproteinase 13; D020780:Matrix Metalloproteinase 9