Dimethylfumarate Inhibits Angiogenesis In Vitro and In Vivo: A Possible Role for Its Antipsoriatic Effect?
Dimethylfumarate Inhibits Angiogenesis In Vitro and In Vivo: A Possible Role for Its Antipsoriatic Effect?
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DOI：
10.1038/jid.2010.416
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发表时间：
2011-06-01
影响因子：
6.5
通讯作者：
Quesada, Ana R.
中科院分区：
文献类型：
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作者：
Garcia-Caballero, Melissa;Mari-Beffa, Manuel;Quesada, Ana R.
富马酸酯（FAEs）已用于口服治疗牛皮癣约50年。鉴于持续和维持的血管生成与包括牛皮癣在内的几种皮肤疾病有关，我们在研究中寻求通过研究FAEs是否能够干扰血管生成机制来进一步了解其作用机制。我们的研究结果表明，富马酸二甲基（DMF）抑制内皮细胞的某些功能，即分化、增殖和迁移。类似浓度的富马酸一甲基或富马酸没有表现出这种活性。我们的数据表明，DMF以剂量依赖的方式抑制转化和非转化细胞的生长。这种化合物对增殖内皮细胞的生长抑制作用可能是由于，至少部分是由于诱导细胞凋亡。DMF对上述体外血管生成基本步骤的抑制作用与在体内观察到的血管生成抑制作用是一致的，这是通过鸡绒毛膜尿囊膜和斑马鱼活体荧光胚胎新生血管实验证实的。DMF的抗血管生成活性可能有助于该化合物的抗银屑病、抗肿瘤和抗转移活性，并表明其在治疗血管生成相关恶性肿瘤方面的潜力。
The fumaric acid esters (FAEs) have been used for the oral treatment of psoriasis for some 50 years. Given that a persistent and maintained angiogenesis is associated with several cutaneous diseases, including psoriasis, we sought in our study to gain further insight into their mechanism of action by investigating whether FAEs are able to interfere with angiogenesis mechanisms. Our results demonstrate that dimethylfumarate (DMF) inhibits certain functions of endothelial cells, namely, differentiation, proliferation, and migration. This activity was not exhibited by similar concentrations of monomethylfumarate or fumaric acid. Our data indicate that DMF inhibits the growth of transformed and nontransformed cells in a dose-dependent manner. The growth-inhibitory effect exerted by this compound on proliferating endothelial cells could be due, at least in part, to an induction of apoptosis. Inhibition by DMF of the mentioned essential steps of in vitro angiogenesis is consistent with the observed inhibition of in vivo angiogenesis, substantiated using chick chorioallantoic membrane and live fluorescent zebrafish embryo neovascularization assays. The antiangiogenic activity of DMF may contribute to the antipsoriatic, antitumoral, and antimetastatic activities of this compound and suggests its potential in the treatment of angiogenesis-related malignancies.