Demonstration of Inhibitory Effect of Oral Shark Cartilage on Basic Fibroblast Growth Factor-Induced Angiogenesis in the Rabbit Cornea.

Abstract

Angiogenesis is a multistep and redundant process crucial in several physiological events and pathophysiological developments such as cancer. Since the early findings by Folkman et al. that tumor growth is dependent on new vascularization, it is now broadly accepted that solid tumors cannot grow beyond 1-2 mm without a vascular supply of oxygen and nutrients.1) Further, there is a substantial body of evidence indicating that attacking tumor neovascularization is a promising approach in the treatment of cancer.2)The acquisition of an angiogenic phenotype in endothelial cells requires that angiogenic factors be overexpressed and released by cancer cells and host cells. These factors include fibroblastic growth factors and vascular endothelial growth factors that bind to specific receptors on the endothelial cell surface stimulating their migration and proliferation.3,4) On the other hand, the migration and organization of endothelial cells in capillary structures depend on the activity of the pericellular fibrinolytic system and the overexpression of different cellular adhesion molecules.5) All these events in the angiogenic process afford potential targets for an antiangiogenic therapy.Many compounds derived from various natural sources have been found to have antiangiogenic effects using both in vitro and in vivo models. 6) These compounds include extracts and fractions from cartilage. 7) Cartilage is an avascular tissue, and for this reason was believed to contain compounds with antiangiogenic activity. This hypothesis was first tested in 1973 by Eisenstein et al., who reported that cartilage extracted with guanidine 1 M did not resist to becoming vascularized when placed on the chick chorioallantoic membrane (CAM).8) It was later demonstrated by Folkman and Ingber that cartilage could inhibit tumor-induced angiogenesis in the CAM model. 9) Based on those works, recent studies have shown that substances isolated from shark cartilage, for example U-995 and AE-941, inhibit angiogenesis and tumor growth in vivo. 10,11) Fontenele et al. recently described analgesic and antiinflammatory properties of a water soluble fraction (WSF) of shark cartilage that was attributed principally to a small peptide with a molecular weight of 2.3 KDa.12) In the latter work these in vivo pharmacological effects were observed with oral as well as intraperitoneally administration.The aims of the present study were a) to demonstrate the ability of oral shark cartilage to exert an inhibitory effect on rabbit cornea neovascularization induced by basic fibroblast growth factor (bFGF), and b) to examine in the same model a newly described bioactive fraction of shark cartilage for antiangiogenic activity. Several angiogenic inhibitors have been obtained from shark cartilage, some of these are currently in clinical trials for assessment of safety and therapeutic efficacy in humans. Still, shark cartilage taken orally is commonly used in alternative and complimentary medicine for various ailments including serious diseases such as cancer. Howe...

Inhibition of Corneal Neovascularization by Hydrazinocurcumin

“…Therefore, corneal neovascularisation induced through two intrastromal implantations of VEGF polymer serves as a suitable animal model for the study of inflammatory corneal neovascularization. There are a number of natural products known to possess antiangiogenic properties which include genistein [22], shark cartilage [23], curcumin [24,25], propolis extract [26] and AME [14][15][16][17].…”

Signaling through JAM-1 and αvβ3 is required for the angiogenic action of bFGF: dissociation of the JAM-1 and αvβ3 complex

“…8 For this reason, many therapeutic agents generated to block growth factor-induced angiogenesis are now in clinical trials. 9,10 Among the integrin family members most widely studied in the angiogenic process are of the ␣ v family-integrins ␣ v ␤ 3 and ␣ v ␤ 5 , which are receptors for vitronectin. 4,[11][12][13] These 2 integrins regulate 2 distinct pathways of angiogenesis.…”

Ingestion of Proteoglycan Fraction from Shark Cartilage Increases Serum Inhibitory Activity against Matrix Metalloproteinase-9 and Suppresses Development of N-Nitrosobis(2-oxopropyl)amine-Induced Pancreatic Duct Carcinogenesis in Hamster

“…It has been demonstrated that oral administration of shark cartilage and its extracts suppress carcinogenesis, − growth of tumor, , and also angiogenesis in animal models. Angiogenesis is the formation of new capillaries from the established veins, which plays significant role in tumor growth and carcinogenesis .…”