Arakaki Naokatu, Toyofuku Ayako, Emoto Yuka, Nagao Tomoko, Kuramoto Yoshinori, Shibata Hirofumi, Higuti Tomihiko
Pharmceutical Sciences, The University of Tokushima, Shomachi, Tokushima 770-8505, Japan.
Biochem Cell Biol. 2004 Oct;82(5):583-8. doi: 10.1139/o04-057.
Dietary flavonoids have demonstrated anti-carcinogenic activity in several animal models, but their mechanisms of action have not yet been clearly established. Here, we show that flavone, a parent compound of flavonoids, inhibits the proliferation, migration, and capillary tube formation of human umbilical vein endothelial cells (HUVECs). Flow cytometric analysis showed that flavone arrests the cell cycle progression at G(1) phase in HUVECs. We observed the down-regulation of the hyperphosphorylated form of retinoblastoma gene product and cyclin-dependent kinases 2 and 4 in flavone-treated cells, but it had no affect on the expression of p53 and cyclin-dependent kinase inhibitors p21(CIP/Waf1) and p27(Kip). Flavone almost completely inhibited the activation of extracellular signal regulated kinase 1. The present results suggest that the flavone moiety of flavonoids is required for anti-proliferative activity of flavonoids and that anti-carcinogenic action of flavonoids in vivo was mediated, at least in part, by inhibiting angiogenesis.
膳食类黄酮已在多种动物模型中显示出抗癌活性，但其作用机制尚未明确。在此，我们表明黄酮（类黄酮的母体化合物）可抑制人脐静脉内皮细胞（HUVECs）的增殖、迁移和毛细血管管腔形成。流式细胞术分析表明，黄酮使HUVECs的细胞周期进程停滞于G(1)期。我们观察到在黄酮处理的细胞中，视网膜母细胞瘤基因产物以及细胞周期蛋白依赖性激酶2和4的过度磷酸化形式表达下调，但对p53以及细胞周期蛋白依赖性激酶抑制剂p21(CIP/Waf1)和p27(Kip)的表达没有影响。黄酮几乎完全抑制了细胞外信号调节激酶1的激活。目前的结果表明，类黄酮的黄酮部分是类黄酮抗增殖活性所必需的，并且类黄酮在体内的抗癌作用至少部分是通过抑制血管生成介导的。
