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Cancer Health Center

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Cartilage (Bovine and Shark) (PDQ®): Complementary and alternative medicine - Health Professional Information [NCI] - History


The process of angiogenesis requires at least four coordinated steps, each of which may be a target for inhibition. First, tumors must communicate with the endothelial cells that line the inside of nearby blood vessels. This communication takes place, in part, through the secretion of angiogenesis factors such as vascular endothelial growth factor.[14,15,16,17,18] Second, the activated endothelial cells must divide to produce new endothelial cells, which will be used to make the new blood vessels.[15,17,18,19,20] Third, the dividing endothelial cells must migrate toward the tumor.[15,16,17,18,19,20] To accomplish this, they must produce enzymes called matrix metalloproteinases, which will help them carve a pathway through the tissue elements that separate them from the tumor.[18,19,20,21,22] Fourth, the new endothelial cells must form the hollow tubes that will become the new blood vessels.[17,18] Some angiogenesis inhibitors may be able to block more than one step in this process.

Cartilage is relatively resistant to invasion by tumor cells,[23,24,25,26,27,28,29,30] and tumor cells use matrix metalloproteinases when they migrate during the process of metastasis.[21,25,31,32] Therefore, if the angiogenesis inhibitors in cartilage are also inhibitors of matrix metalloproteinases, then the same molecules may be able to block both angiogenesis and metastasis. Shark tissues other than cartilage have also been reported to produce antitumor substances.[33,34,35,36]


  1. Houck JC, Jacob RA, Deangelo L, et al.: The inhibition of inflammation and the acceleration of tissue repair by cartilage powder. Surgery 51: 632-8, 1962.
  2. Prudden JF, Balassa LL: The biological activity of bovine cartilage preparations. Clinical demonstration of their potent anti-inflammatory capacity with supplementary notes on certain relevant fundamental supportive studies. Semin Arthritis Rheum 3 (4): 287-321, 1974 Summer.
  3. Prudden JF, Migel P, Hanson P, et al.: The discovery of a potent pure chemical wound-healing accelerator. Am J Surg 119 (5): 560-4, 1970.
  4. Cassileth BR: Shark and bovine cartilage therapies. In: Cassileth BR, ed.: The Alternative Medicine Handbook: The Complete Reference Guide to Alternative and Complementary Therapies. New York, NY: WW Norton & Company, 1998, pp 197-200.
  5. Fontenele JB, Araújo GB, de Alencar JW, et al.: The analgesic and anti-inflammatory effects of shark cartilage are due to a peptide molecule and are nitric oxide (NO) system dependent. Biol Pharm Bull 20 (11): 1151-4, 1997.
  6. Langer R, Brem H, Falterman K, et al.: Isolations of a cartilage factor that inhibits tumor neovascularization. Science 193 (4247): 70-2, 1976.
  7. Prudden JF: The treatment of human cancer with agents prepared from bovine cartilage. J Biol Response Mod 4 (6): 551-84, 1985.
  8. Romano CF, Lipton A, Harvey HA, et al.: A phase II study of Catrix-S in solid tumors. J Biol Response Mod 4 (6): 585-9, 1985.
  9. Durie BG, Soehnlen B, Prudden JF: Antitumor activity of bovine cartilage extract (Catrix-S) in the human tumor stem cell assay. J Biol Response Mod 4 (6): 590-5, 1985.
  10. Rosen J, Sherman WT, Prudden JF, et al.: Immunoregulatory effects of catrix. J Biol Response Mod 7 (5): 498-512, 1988.
  11. Lee A, Langer R: Shark cartilage contains inhibitors of tumor angiogenesis. Science 221 (4616): 1185-7, 1983.
  12. Miller DR, Anderson GT, Stark JJ, et al.: Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer. J Clin Oncol 16 (11): 3649-55, 1998.
  13. Hunt TJ, Connelly JF: Shark cartilage for cancer treatment. Am J Health Syst Pharm 52 (16): 1756, 1760, 1995.
  14. Folkman J: The role of angiogenesis in tumor growth. Semin Cancer Biol 3 (2): 65-71, 1992.
  15. Sipos EP, Tamargo RJ, Weingart JD, et al.: Inhibition of tumor angiogenesis. Ann N Y Acad Sci 732: 263-72, 1994.
  16. Li CY, Shan S, Huang Q, et al.: Initial stages of tumor cell-induced angiogenesis: evaluation via skin window chambers in rodent models. J Natl Cancer Inst 92 (2): 143-7, 2000.
  17. Alberts B, Bray D, Lewis J, et al.: Molecular Biology of the Cell. 3rd ed. New York, NY: Garland Publishing, 1994.
  18. Moses MA: The regulation of neovascularization of matrix metalloproteinases and their inhibitors. Stem Cells 15 (3): 180-9, 1997.
  19. Stetler-Stevenson WG: Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention. J Clin Invest 103 (9): 1237-41, 1999.
  20. Haas TL, Madri JA: Extracellular matrix-driven matrix metalloproteinase production in endothelial cells: implications for angiogenesis. Trends Cardiovasc Med 9 (3-4): 70-7, 1999 Apr-May.
  21. McCawley LJ, Matrisian LM: Matrix metalloproteinases: multifunctional contributors to tumor progression. Mol Med Today 6 (4): 149-56, 2000.
  22. Mandal M, Mandal A, Das S, et al.: Clinical implications of matrix metalloproteinases. Mol Cell Biochem 252 (1-2): 305-29, 2003.
  23. Takigawa M, Pan HO, Enomoto M, et al.: A clonal human chondrosarcoma cell line produces an anti-angiogenic antitumor factor. Anticancer Res 10 (2A): 311-5, 1990 Mar-Apr.
  24. Ohba Y, Goto Y, Kimura Y, et al.: Purification of an angiogenesis inhibitor from culture medium conditioned by a human chondrosarcoma-derived chondrocytic cell line, HCS-2/8. Biochim Biophys Acta 1245 (1): 1-8, 1995.
  25. Sadove AM, Kuettner KE: Inhibition of mammary carcinoma invasiveness with cartilage-derived inhibitor. Surg Forum 28: 499-501, 1977.
  26. Takigawa M, Shirai E, Enomoto M, et al.: Cartilage-derived anti-tumor factor (CATF) inhibits the proliferation of endothelial cells in culture. Cell Biol Int Rep 9 (7): 619-25, 1985.
  27. Takigawa M, Shirai E, Enomoto M, et al.: A factor in conditioned medium of rabbit costal chondrocytes inhibits the proliferation of cultured endothelial cells and angiogenesis induced by B16 melanoma: its relation with cartilage-derived anti-tumor factor (CATF). Biochem Int 14 (2): 357-63, 1987.
  28. Pauli BU, Memoli VA, Kuettner KE: Regulation of tumor invasion by cartilage-derived anti-invasion factor in vitro. J Natl Cancer Inst 67 (1): 65-73, 1981.
  29. Liang JH, Wong KP: The characterization of angiogenesis inhibitor from shark cartilage. Adv Exp Med Biol 476: 209-23, 2000.
  30. Suzuki F: Cartilage-derived growth factor and antitumor factor: past, present, and future studies. Biochem Biophys Res Commun 259 (1): 1-7, 1999.
  31. Murray JB, Allison K, Sudhalter J, et al.: Purification and partial amino acid sequence of a bovine cartilage-derived collagenase inhibitor. J Biol Chem 261 (9): 4154-9, 1986.
  32. Wojtowicz-Praga S: Clinical potential of matrix metalloprotease inhibitors. Drugs R D 1 (2): 117-29, 1999.
  33. Pettit GR, Ode RH: Antineoplastic agents L: isolation and characterization of sphyrnastatins 1 and 2 from the hammerhead shark Sphyrna lewini. J Pharm Sci 66 (5): 757-8, 1977.
  34. Sigel MM, Fugmann RA: Studies on immunoglobulins reactive with tumor cells and antigens. Cancer Res 28 (7): 1457-9, 1968.
  35. Snodgrass MJ, Burke JD, Meetz GD: Inhibitory effect of shark serum on the Lewis lung carcinoma. J Natl Cancer Inst 56 (5): 981-4, 1976.
  36. Pugliese PT, Heinerman J: Devour Disease with Shark Liver Oil. Green Bay, Wis: Impakt Communications, 1999.

This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http:// cancer .gov or call 1-800-4-CANCER.

WebMD Public Information from the National Cancer Institute

Last Updated: 8/, 015
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
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