Marine algal carotenoids inhibit angiogenesis by down-regulating FGF-2-mediated intracellular signals in vascular endothelial cells
Marine algal carotenoids inhibit angiogenesis by down-regulating FGF-2-mediated intracellular signals in vascular endothelial cells
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DOI：
10.1007/s11010-013-1651-5
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发表时间：
2013-08-01
影响因子：
4.3
通讯作者：
Hirata, Takashi
中科院分区：
文献类型：
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作者：
Ganesan, Ponesakki;Matsubara, Kiminori;Hirata, Takashi
发现天然化合物作为有效的血管生成抑制剂已成为预防癌症的重要途径。我们以前证明了两种海藻类胡萝卜素，岩藻黄质和管藻黄质的抗血管生成潜力。在这项研究中，我们评估了这两个类胡萝卜素的抗血管生成活性的分子机制，使用人脐静脉内皮细胞。该研究表明，岩藻黄素和管藻黄素均抑制成纤维细胞生长因子2（FGF-2）及其受体（FGFR-1）以及它们的反式激活因子EGR-1的mRNA表达。但这两种类胡萝卜素对VEGFR-2 mRNA的表达无明显影响。此外，这两种海藻类胡萝卜素下调FGF-2介导的细胞内信号蛋白如ERK 1/2和Akt的磷酸化。这些类胡萝卜素对FGF-2介导的细胞内信号蛋白的抑制抑制了内皮细胞的迁移以及它们在基质胶上分化成管状结构。这些结果首次证明了岩藻黄质和管黄质的抗血管生成作用的潜在可能分子机制，并表明这些作用是由于FGFR-1下调信号转导。我们的研究结果意味着对海藻类胡萝卜素的新生物功能特性的新见解，这将改善目前在治疗癌症和其他促血管生成疾病中的抗血管生成疗法。
Discovery of natural compounds as effective angiogenesis inhibitors has become an important approach in the prevention of cancer. We previously demonstrated the anti-angiogenic potential of two marine algal carotenoids, fucoxanthin and siphonaxanthin. In this study, we evaluated the molecular mechanisms of the anti-angiogenic activity of those two carotenoids using human umbilical vein endothelial cells. This study showed that both fucoxanthin and siphonaxanthin suppress the mRNA expression of fibroblast growth factor 2 (FGF-2) and its receptor (FGFR-1) as well as their trans-activation factor, EGR-1. But, the mRNA expression of VEGFR-2 did not show significant effect by those two carotenoids. Further, those two marine algal carotenoids down-regulate the phosphorylation of FGF-2-mediated intracellular signaling proteins such as ERK1/2 and Akt. Inhibition of FGF-2-mediated intracellular signaling proteins by those carotenoids represses the migration of endothelial cells as well as their differentiation into tube-like structures on Matrigel. These results demonstrate for the first time the possible molecular mechanism underlying the anti-angiogenic effects of fucoxanthin and siphonaxanthin and suggest that these effects are due to the down-regulation of signal transduction by FGFR-1. Our findings imply a new insight into the novel bio-functional property of marine algal carotenoids which should improve current anti-angiogenic therapies in the treatment of cancer and other pro-angiogenic diseases.