Title:Apoptotic Potency of Angiostatic Compounds in the Treatment of Cancer
Volume: 13
Issue: 11
Author(s): Esther Raskopf, Tilman Sauerbruch and Volker Schmitz
Affiliation:
Keywords:
Hepatocellular carcinoma, tumour-angiogenesis, angiostatic therapy, RNA-interference, tyrosine kinase inhibitors,
endogenous angiogenesis inhibitors, nutrient deficiency, vascular endothelial growth factor (VEGF), cancer, hepatocellular carcinoma, pro-apoptotic potency
Abstract: When tumours outgrow their vascular supply, they become hypoxic because of nutrient deficiency. This increases
the expression and secretion of proangiogenic factors, like vascular endothelial growth factor (VEGF), leading to
the activation of endothelial cells. The activated endothelial cells migrate, proliferate and form new blood vessels, resulting
in increased tumour growth. This process is called tumour angiogenesis. Inhibiting tumour angiogenesis and therefore
tumour growth is a well known concept in the treatment of cancer, such as hepatocellular carcinoma (HCC). This can be
done by endogenous angiogenesis inhibitors, like angiostatin and its derivates. These are known to affect endothelial cell
functions including the induction of apoptosis. The impact of these angiostatic factors on the cell is manifold. This also
applies for so called small molecules, which affect tyrosine kinases such as receptors or intracellular signal transduction
proteins. Other approaches, like monoclonal antibodies, target a single molecule, mainly VEGF, to inhibit receptorbinding
and downstream signal transduction. Gene silencing, mainly via RNA interference (RNAi) intervenes on RNAlevel,
leading to reduced gene expression and protein secretion. Due to intense research in this field, there is rising evidence
that also tumour cells themselves are influenced by angiostatic treatment approaches and the underlying molecular
mechanisms are more and more revealed. Here we give a (short) review regarding the pro-apoptotic potency of antiangiogenic
compounds like angiostatic molecules, sequestering antibodies, small molecules and RNAi approaches targeting
endothelial and tumour cell survival to inhibit angiogenesis and tumour growth.
