Dimethylfumarate Inhibits Angiogenesis In Vitro and In Vivo: A Possible Role for Its Antipsoriatic Effect?

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.