Shark cartilage extract interferes with cell adhesion and induces reorganization of focal adhesions in cultured endothelial cells

Abstract

In this study, we examined the effects of shark cartilage extract on the attachment and spreading properties and the focal adhesion structure of cultured bovine pulmonary artery endothelial cells. Treatment with cartilage extract resulted in cell detachment from the substratum. Immunofluorescence staining of those treated cells that remained attached showed that, instead of being present in both central and peripheral focal adhesions as in control cells, both integrin alpha(v)beta(3) and vinculin were found only in peripheral focal adhesion and thinner actin filament bundles were seen. In addition to causing cell detachment, cartilage extract partially inhibited the initial adherence of the cells to the substratum in a dose-dependent manner. Integrin alpha(v)beta(3) and vinculin staining of these cells also showed a peripheral focal adhesion distribution pattern. Vitronectin induced cell spreading in the absence of serum, but was blocked by simultaneous incubation with cartilage extract, which was shown to inhibit both integrin alpha(v)beta(3) and vinculin recruitment to focal adhesion and the formation of stress fibers. Dot binding assays showed that these inhibitory effects on cell attachment and spreading were not due to direct binding of cartilage extract components to integrin alpha(v)beta(3) or vitronectin. Shark cartilage chondroitin sulfate had no inhibitory effect on either cell attachment or spreading of endothelial cells. These results show that the inhibitory effects of cartilage extract on cell attachment and spreading are mediated by modification of the organization of focal adhesion proteins.

A novel polypeptide from shark cartilage with potent anti-angiogenic activity

“…Recent clinical evaluation showed no improvement in quality of life for patients with advanced cancer who received shark cartilage, 4 despite strong evidence that shark cartilage polypeptides have potent anti-angiogenic activity. [31][32][33] There exist several possibilities for the ineffectiveness in clinical studies. First, crude extracts of complex natural products such as shark cartilage generally vary in composition, due to differences in genetic makeup, seasonal and environmental factors, as well as the isolation methods employed.…”

The role of nutraceutical proteins and peptides in apoptosis, angiogenesis, and metastasis of cancer cells

“…Several in vitro and in vivo studies show that SC plays an important role in preventing the spread of cancer by its ability to inhibit angiogenesis. The proposed mechanisms of action involved in this antiangiogenic effect of SC included inhibition of bFGFinduced angiogenesis in the Matrigel mouse model [95], prevention of collagenase-induced collagenolysis [96], increase T cell infiltration into the tumor [97,98], and inhibition of cell adhesion through modification of focal adhesion proteins [99]. The anti-angiogenic property of SC was also demonstrated by several studies using the CAM ex ovo model [100][101][102][103].…”

Induction of inflammatory cytokines by cartilage extracts

“…While the initial interest in shark cartilage related to its alleged anticancer properties [6][7][8][9][10][11], recently, the interest is on the effect of shark cartilage on oxidative stress [12,13], the expression of adhesion molecules and fibrinolytic enzymes [14,15], and on immune function [16][17][18]. For these studies, shark cartilage has been purified preparations rather than commercial preparations of shark cartilage that are taken as oral supplements by consumers for therapeutic and/or prophylactic purposes.…”