Evidence for the Effects of Xanthohumol in Disrupting Angiogenic, but not Stable Vessels

Angiogenesis is a complex multistep process that comprises proliferation, migration, and anastomosis of endothelial cells, followed by stabilization of the newly formed vessel through the attachment of support cells. This process is imbalanced in a large number of disorders, including cardiovascular disease, diabetes and cancer. Evidence indicates that xanthohumol (XN), a prenylated chalcone present in beer, exerts anti-angiogenic properties. However, its precise effect within the angiogenic steps is not accurately established. The purpose of the present study was to examine which features of the angiogenic process can be disturbed by XN. Human umbilical vein endothelial cells (HUVEC) and human fetal aortic smooth muscle cells (SMC) were incubated with xanthohumol at 5 and 10 μM, and cell viability, apoptosis, invasion and capillary-like structures formation were examined. Treatment with 10 μM XN significantly decreased viability and invasion capacity and increased apoptosis in both cell types as assessed by MTT, double-chamber assay and TUNEL assay respectively. The two concentrations of XN further led to a significant reduction in the number of capillary-like structures, when HUVEC were cultured on growth factor reduced-Matrigel-coated plates. Interestingly, XN exhibited the opposite effect when HUVEC were co-cultured with SMC, leading to an increase in the number of cord structures. In addition, incubation of both types of cells with XN resulted in reduced activity of NFκB, a transcription factor implicated in these cell fates. Given the absence of adverse effects in mature vasculature by XN, these findings emphasize the potential use of XN against pathological situations where angiogenesis is stimulated.