Coupling In vitro and In vivo Paradigm Reveals a Dose Dependent Inhibition of Angiogenesis Followed by Initiation of Autophagy by C6-Ceramide

摘要: The activity of N-hexanoyl-D-erythro-sphingosine, a C6-ceramide against angiogenesis was tested in vitro and vivo. effect ceramide inhibiting MCF-7 cancer cells also determined. aim this study to potentiate the as anti-angiogenic compound that can regulate tumor induced angiogenesis. inhibited vascular endothelial growth factor (VEGF)-induced human umbilical vein (HUVEC) tube formation dose-dependent manner within 24 hours. Ceramide at concentrations between 12.5 25 μM viability reduced VEGF-induced cell migration At 50 μM, death via autophagy demonstrated by accumulation MDC ceramide-treated vacuoles. expression VEGF levels cathepsin D increased. In vivo, caused 40% reduction new vessel CAM assay Zebrafish exposed 100 - 400 had distinct disruption blood development 48 hours post-fertilization. Ceramide-exposed embryos primary motoneurons exhibiting abnormal axonal trajectories ectopic branching. cell-death not detected zebrafish assay. Collectively, these data indicate is potent mechanism underlying its capabilities does rely upon induction apoptosis.