Liu Jun-Jen, Huang Tien-Shang, Cheng Wen-Fang, Lu Fung-Jou
Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.
Department of Internal Medicine, College of Medicine, National Taiwan University and National Taiwan University Hospital, Taipei, Taiwan, Republic of China.
Int J Cancer. 2003 Sep 10;106(4):559-565. doi: 10.1002/ijc.11267.
In recent studies, we have shown that baicalein and baicalin, 2 major flavonoids of Scutellaria baicalensis Georgi, exhibit anticancer activity against several cancers in vitro. In our present study, we assessed their potential as anti-angiogenic agents in vivo employing chicken chorioallantoic membrane (CAM) assay and in vitro human umbilical vein endothelial cells (HUVECs) culture. When CAMs were treated with either baicalein or baicalin for 48 hr, the angiogenic response induced by basic fibroblast growth factor (bFGF) was markedly reduced in a dose-dependent manner. Further characterization showed that both flavonoids exhibited dual antiproliferative (at low dose) and apoptogenic (at high dose) effects on HUVECs. In biochemical analysis, treatment of HUVECs with baicalein and baicalin for 24 hr resulted in a dose-dependent decrease in the matrix metalloproteinase (MMP)-2 activity. Moreover, the migration of endothelial cells and the differentiation of endothelial cells into branching networks of tubular structures in vitro were also inhibited by these 2 flavonoids in a dose-dependent manner. Baicalein is more potent than baicalin in anti-angiogenesis in vivo as well as in vitro. Taken together, the results of our study provide evidence that baicalein and baicalin possess an anti-angiogenesis potential that is a previously unrecognized biologic activity.
在最近的研究中，我们已表明，黄芩的两种主要黄酮类化合物黄芩素和黄芩苷在体外对多种癌症具有抗癌活性。在本研究中，我们通过鸡胚绒毛尿囊膜（CAM）试验在体内以及人脐静脉内皮细胞（HUVECs）体外培养，评估了它们作为抗血管生成剂的潜力。当用黄芩素或黄芩苷处理CAM 48小时时，碱性成纤维细胞生长因子（bFGF）诱导的血管生成反应以剂量依赖性方式显著降低。进一步的特性分析表明，这两种黄酮类化合物对HUVECs均表现出双重抗增殖（低剂量时）和诱导凋亡（高剂量时）作用。在生化分析中，用黄芩素和黄芩苷处理HUVECs 24小时导致基质金属蛋白酶（MMP）-2活性呈剂量依赖性降低。此外，这两种黄酮类化合物在体外也以剂量依赖性方式抑制内皮细胞的迁移以及内皮细胞分化为管状结构的分支网络。黄芩素在体内和体外抗血管生成方面比黄芩苷更有效。综上所述，我们的研究结果提供了证据，表明黄芩素和黄芩苷具有抗血管生成潜力，这是一种以前未被认识的生物学活性。
