An ethanolic extract from a shark having potent anti-angiogeneric activity: its anti-angiogenic mechanism and clinical application

1. 1 Dept. of Food Science and Nutrition Pusan National University
2. 2 Grekin Skin Institute Oakwood Southshore Medical Center Wyandotte Michigan
3. 3 Immuno research Ltd. Auckland, New Zealand.

Abstract

An ethanol extract from shark muscle has been shown to have potent angiogenic activity when mixed together with olive oil in a ratio of 1 part extract to 9 parts olive oil. This mixture has been given the trade name SuperMaco (SMO).

The anti-angiogenic activity was evident in both in vitro and in vivo studies in rats. When combined with the known angiogenic stimulatory growth factors Vascular Endothelial Growth Factor (VEGF), Platelet Derived Growth Factor (PDGF), Transforming Growth Factor-Beta (TGF-β) and Fibroblast Growth Factor-2 (FGF-2), SMO completely eliminated the stimulation induced by these growth factors. Possible mechanisms for this activity are that SMO is competing for receptor sites on the endothelial cell surface by preferential binding to those sites or by binding to the growth factors themselves.

Studies were conducted using soluble forms of VEGF-R1 and VEGF-R2 and it was found that SMO inhibited complex formation of the VEGF with both receptors. This inhibitory effect by SMO was enhanced when SMO was pre-incubated with VEGF receptors.

In another study, the effect of SMO on VEGF receptor phosphorylation using human umbilical vein endothelial cells (HUVEC) and a human breast carcinoma cell line (MDA-MB-231) was investigated. The in vitro cell proliferation assay indicated that SMO reversed the increase in VEGF promoted cell proliferation in both HUVEC and MDA-MB-231 cells. Using Western Blot analysis it was observed that SMO significantly inhibited VEGF promoted VEGF receptor-1, VEGF receptor-2 and tyrosine phosphorylation in HUVEC and MDA-MB-231 cells in a dose related manner. These results suggest that SMO appears to block the binding of VEGF with the receptors and inhibit the signal transduction pathways.
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