Curcumin inhibits the formation of capillary-like tubes by rat lymphatic endothelial cells
Curcumin inhibits the formation of capillary-like tubes by rat lymphatic endothelial cells
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DOI：
10.1016/j.canlet.2006.11.027
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发表时间：
2007-06-28
期刊：
影响因子：
9.7
通讯作者：
Saiki, Ikuo
中科院分区：
文献类型：
--
作者：
Matsuo, Mitsuhiro;Sakurai, Hiroaki;Saiki, Ikuo
天然色素姜黄素和小檗碱已被证明具有多种药理作用，包括抗炎，抗癌和抗转移特性。在这里，我们研究了抗淋巴管生成的作用，在体外管形成模型，使用条件永生化的淋巴管内皮TR-LE细胞，一个新建立的细胞系，起源于胸导管的转基因大鼠表达的温度敏感性SV 40大T抗原。姜黄素，而不是小檗碱，表现出剂量依赖性抑制TR-LE细胞形成毛细血管样管，而不影响细胞活力和粘附基质胶。为了阐明所涉及的分子机制，我们进行了针对姜黄素推定靶点的特异性抑制剂的实验，包括1 κ B激酶（IKK）、表皮生长因子受体（EGFR）、磷脂酰肌醇-3激酶（PI 3 K）/Akt和基质金属蛋白酶（MMPs）。虽然IKK-2抑制剂VI和EGFR酪氨酸激酶抑制剂吉非替尼和PD 153035没有效果，但PI 3 K抑制剂LY 294002和MMP抑制剂GM 6001都使输卵管缩短了约50%。蛋白质印迹分析和明胶酶谱显示，姜黄素，而不是小檗碱，有抑制作用的Akt的磷酸化和MMP-2的酶活性在TR-LE细胞。这些结果表明，姜黄素发挥其抑制淋巴管生成的作用，部分通过Akt和MMP-2。(C)2006爱思唯尔爱尔兰有限公司保留所有权利。
The natural pigments curcumin and berberine have been shown to exhibit a variety of pharmacologic effects including anti-inflammatory, anti-cancer, and anti-metastatic properties. Here, we investigated the anti-lymphangiogenic effect with an in vitro tube-forming model using conditionally immortalized lymphatic endothelial TR-LE cells, a newly established cell line originating from the thoracic duct of a transgenic rat expressing the temperature-sensitive SV40 large T-antigen. Curcumin, but not berberine, exhibited a dose-dependent inhibition of the formation of capillary-like tubes by TR-LE cells without affecting cell viability and adhesion to Matrigel. To address the molecular mechanisms involved, we performed experiments with specific inhibitors against putative targets of curcumin, including 1 kappa B kinase (IKK), epidermal growth factor receptor (EGFR), phosphatidylinositol-3 kinase (PI3K)/Akt, and matix metalloproteinases (MMPs). While the IKK-2 inhibitor VI and EGFR tyrosine kinase inhibitors gefitinib and PD153035 had no effect, both the PI3K inhibitor LY294002 and the MMP inhibitor GM6001 shortened the tubes by approximately 50%. Western blot analysis and gelatin zymography revealed that curcumin, but not berberine, has an inhibitory effect on the phosphorylation of Akt and enzymatic activity of MMP-2 in TR-LE cells. These results suggest that curcumin exerts its inhibitory effect on lymphangiogenesis partly through Akt and MMP-2. (C) 2006 Elsevier Ireland Ltd. All rights reserved.