Department of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Republic of Korea.
Carcinogenesis. 2010 May;31(5):911-7. doi: 10.1093/carcin/bgp221. Epub 2009 Dec 11.
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.
杨梅素是洋葱、浆果和红酒中的主要植物化学物质之一。先前的研究表明，杨梅素有很强的抗癌和化学预防作用。本研究探讨了杨梅素对紫外线（UV）B 诱导的 SKH-1 无毛小鼠皮肤肿瘤发生模型中血管生成的影响。杨梅素的局部治疗抑制了 SKH-1 无毛小鼠皮肤中重复的 UVB 诱导的新血管生成。杨梅素处理显著抑制慢性 UVB 照射诱导的血管内皮生长因子、基质金属蛋白酶（MMP）-9 和 MMP-13 的表达。免疫组织化学和 Western blot 分析显示，杨梅素抑制了 UVB 诱导的小鼠皮肤缺氧诱导因子-1α的表达。Western blot 分析和激酶测定数据显示，杨梅素抑制了 UVB 诱导的磷脂酰肌醇-3（PI-3）激酶活性，并随后减弱了 UVB 诱导的小鼠皮肤裂解物中 Akt/p70(S6K)的磷酸化。下拉测定显示 PI-3 激酶和杨梅素在小鼠皮肤裂解物中的直接结合。我们的结果表明，杨梅素通过调节体内小鼠皮肤中的 PI-3 激酶活性来抑制 UVB 诱导的血管生成。
