Studies on cartilage-derived inhibitors of angiogenesis

"This work arose from anecdotal evidence for the existence of anti-angiogenic factors in shark cartilage powders. The project aimed to elucidate the mechanisms of anti-angiogenesis of shark cartilage, identify at least one novel anti-angiogenic factor from shark cartilage, and search for other natural anti-angiogenic factors in cartilage of other species." -- abstract.. This work arose from anecdotal evidence for the existence of anti-angiogenic factors in shark cartilage powders. The project aimed to elucidate the mechanisms of anti-angiogenesis of shark cartilage, identify at least one novel anti-angiogenic factor from shark cartilage, and search for other natural anti-angiogenic factors in cartilage of other species. The goals of the work have been successfully achieved. Firstly, a large number of commercially available shark cartilage powders have been investigated and it was found that 22% of samples tested showed no anti-angiogenic activity (CAM assay), while the remaining 78% showed variable anti-angiogenic activity. Secondly, cartilage from other species including emu, ostrich, deer, camel, crocodile and kangaroo have been investigate, and most were found to be bioactive in anti-angiogenesis. The screening potency of the bioactive agents not only varied between different cartilage depots in the one species but also varied between species. Bioactive fractions comparable in activity to those of shark were obtained from crocodile ischeum. In contrast, cartilage fractions obtained from the ostrich sternum and camel nasal septum did not show any anti-angiogenic activities. Mammalian representatives (deer, camel and kangaroo) in this study all had cartilage depots which provided variable bioactivity. Kangaroo rib and camel ear seem likely to be promising substitutes for shark cartilage if considering the efficiency of cartilage collection and availability and together with potency. Thirdly, mechanisms of anti-angiogenesis of shark cartilage have been investigated, it was found that shark cartilage inhibits angiogenesis on CAM by blocking heparin-binding of bFGF with heparin sulfate proteoglycans (HSPGs) on the surface of endothelial cells involving nitric oxide (NO). Finally, two active fractions have been isolated from shark cartilage, high anti-angiogenic activity has been shown in the bioassay, two proteins purified from these two active fractions were demonstrated on SDS-PAGE. The implications of these findings in terms of further scientific research and the cartilage trade are discussed_