PUBLICATION
Coupling In vitro and In vivo Paradigm Reveals a Dose Dependent Inhibition of Angiogenesis Followed by Initiation of Autophagy by C6-Ceramide
- Authors
- Bansode, R.R., Ahmedna, M., Svoboda, K.R., and Losso, J.N.
- ID
- ZDB-PUB-110613-13
- Date
- 2011
- Source
- International journal of biological sciences 7(5): 629-644 (Journal)
- Registered Authors
- Svoboda, Kurt
- Keywords
- ceramide, angiogenesis, zebrafish, MCF-7 cell-line, VEGF, apoptosis, autophagy
- MeSH Terms
-
- Angiogenesis Inhibitors/pharmacology*
- Animals
- Apoptosis/drug effects
- Autophagy/drug effects*
- Cell Line
- Cell Line, Tumor
- Cell Proliferation/drug effects
- Cell Survival/drug effects
- Ceramides/pharmacology*
- Chick Embryo
- Enzyme-Linked Immunosorbent Assay
- Humans
- Signal Transduction/drug effects
- Vascular Endothelial Growth Factor A/metabolism
- Zebrafish
- PubMed
- 21647331 Full text @ Int. J. Biol. Sci.
Citation
Bansode, R.R., Ahmedna, M., Svoboda, K.R., and Losso, J.N. (2011) Coupling In vitro and In vivo Paradigm Reveals a Dose Dependent Inhibition of Angiogenesis Followed by Initiation of Autophagy by C6-Ceramide. International journal of biological sciences. 7(5):629-644.
Abstract
The activity of N-hexanoyl-D-erythro-sphingosine, a C6-ceramide against angiogenesis was tested in vitro and in vivo. The effect of ceramide in inhibiting MCF-7 cancer cells was also determined. The aim of this study was to potentiate the effect of ceramide as anti-angiogenic compound that can regulate tumor induced angiogenesis.C6-ceramide inhibited vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cells (HUVEC) tube formation in a dose-dependent manner within 24 hours. Ceramide at concentrations between 12.5 and 25 μM inhibited the viability of MCF-7 cells and reduced VEGF-induced cell migration in 24 hours. At 50 μM, ceramide induced MCF-7 cell death via autophagy as demonstrated by accumulation of MDC in ceramide-treated MCF-7 vacuoles. The expression of VEGF was reduced and the levels of cathepsin D in MCF-7 increased. In vivo, 50 μM ceramide caused a 40% reduction of new vessel formation in the CAM assay within 24 hours. Zebrafish exposed to 100 - 400 μM ceramide had a distinct disruption of blood vessel development at 48 hours post-fertilization. Ceramide-exposed embryos also had primary motoneurons exhibiting abnormal axonal trajectories and ectopic branching. Ceramide induced cell-death was not detected in the zebrafish assay. Collectively, these data indicate that ceramide is a potent anti-angiogenic compound and that the mechanism underlying its anti-angiogenic capabilities does not rely upon the induction of apoptosis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping