GENISTEIN, A DIETARY-DERIVED INHIBITOR OF INVITRO ANGIOGENESIS
GENISTEIN, A DIETARY-DERIVED INHIBITOR OF INVITRO ANGIOGENESIS
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DOI：
10.1073/pnas.90.7.2690
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发表时间：
1993-04-01
影响因子：
11.1
通讯作者：
SCHWEIGERER, L
中科院分区：
文献类型：
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作者：
FOTSIS, T;PEPPER, M;SCHWEIGERER, L
食用植物性饮食可以预防与广泛新生血管相关的慢性疾病的发展和进展；然而，人们对其机制知之甚少。为了确定预防是否与饮食衍生的血管生成抑制剂有关，我们对食用植物性饮食的健康受试者的尿液进行了分级，并检查了他们抑制血管内皮细胞增殖的能力。利用气相色谱-质谱法，我们发现其中一个最有效的部位含有几个异黄酮类化合物，我们随后合成了这些异黄酮类化合物。在所有合成的化合物中，异黄酮类染料木素的抑制作用最强，在抑制内皮细胞增殖和体外血管生成方面的浓度分别为5um和150um。正如我们之前已经证明的，食用植物性饮食的受试者尿液中染料木素的浓度在微摩尔范围内，而服用传统西式饮食的受试者尿液中染料木素的浓度要低30倍。金雀异黄素在素食者尿中的高排泄量和我们目前的结果表明，金雀异黄素可能通过抑制新生血管而有助于植物性饮食对包括实体瘤在内的慢性疾病的预防作用。因此，金雀异黄素可能代表了一类新的饮食衍生抗血管生成化合物的成员。
Consumption of a plant-based diet can prevent the development and progression of chronic diseases that are associated with extensive neovascularization; however, little is known about the mechanisms. To determine whether prevention might be associated with dietary-derived angiogenesis inhibitors, we have fractionated urine of healthy human subjects consuming a plant-based diet and examined the fractions for their abilities to inhibit the proliferation of vascular endothelial cells. Using gas chromatography-mass spectrometry, we showed that one of the most potent fractions contained several isoflavonoids, which we subsequently synthesized. Of all synthetic compounds, the isoflavonoid genistein was the most potent and inhibited endothelial cell proliferation and in vitro angiogenesis at concentrations giving half-maximal inhibition of 5 and 150 muM, respectively. As we have previously demonstrated, genistein concentrations in urine of subjects consuming a plant-based diet are in the micromolar range, while those of subjects consuming a traditional Western diet are lower by a factor of >30. The high excretion of genistein in urine of vegetarians and our present results suggest that genistein may contribute to the preventive effect of a plant-based diet on chronic diseases, including solid tumors, by inhibiting neovascularization. Thus, genistein may represent a member of a new class of dietary-derived anti-angiogenic compounds.