Abstract
The synthetic compound fasentin has been described as a modulator of GLUT-1 and GLUT-4 transporters, thus inhibiting glucose uptake in some cancer cells. Endothelial glucose metabolism has been recently connected to angiogenesis and it is now an emerging topic in scientific research. Indeed, certain compounds with a known effect on glucose metabolism have also been shown to inhibit angiogenesis. In this work we tested the capability of fasentin to modulate angiogenesis in vitro and in vivo. We show that fasentin inhibited tube formation in endothelial cells by a mechanism that involves a negative effect on endothelial cell proliferation and invasion, without affecting other steps related to the angiogenic process. However, fasentin barely decreased glucose uptake in human dermal microvascular endothelial cells and the GLUT-1 inhibitor STF-31 failed to inhibit tube formation in these cells. Therefore, this modulatory capacity on endothelial cells function exerted by fasentin is most likely independent of a modulation of glucose metabolism. Taken together, our results show a novel biological activity of fasentin, which could be evaluated for its utility in cancer and other angiogenesis-dependent diseases.
Highlights
The synthetic compound fasentin has been described as a modulator of GLUT-1 and GLUT-4 transporters, inhibiting glucose uptake in some cancer cells
Many factors regulate the angiogenic process, including vascular endothelial growth factor (VEGF), which acts through its receptor VEGFR2, and the fibroblast growth factor (FGF) family, such as FGF-24
The results show that fasentin reduces the number of endothelial cells (ECs), and of tumour cells and, to a lesser extent, fibroblasts, not having a specific effect
Summary
The synthetic compound fasentin has been described as a modulator of GLUT-1 and GLUT-4 transporters, inhibiting glucose uptake in some cancer cells. Fasentin barely decreased glucose uptake in human dermal microvascular endothelial cells and the GLUT-1 inhibitor STF-31 failed to inhibit tube formation in these cells. This modulatory capacity on endothelial cells function exerted by fasentin is most likely independent of a modulation of glucose metabolism. Treatment with fasentin allowed the identification of the potential role of GLUT-1 in glucose uptake in corticotropinomas[6] These results may lead to anti-tumour therapies by targeting glucose metabolism. This fact opens new horizons to treat angiogenesis under pathological conditions through a metabolic approximation instead of just targeting pro-angiogenic molecules[19,20]
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