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

Bovine (cow) cartilage and shark cartilage have been investigated as treatments for people with cancer, psoriasis, arthritis, and a number of other medical conditions for more than 30 years.[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19] At least some of the interest in cartilage as a treatment for people with cancer arose from the mistaken belief that sharks, whose skeletons are made primarily of cartilage, are not affected by this disease.[16,20,21] Although reports of malignant tumors in sharks are rare, a variety of cancers have been detected in these animals.[20,21,22,23] Nonetheless, several substances that have antitumor activity have been identified in cartilage.[2,3,4,7,15,16,17,18,19,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49] More than half a dozen clinical studies of cartilage as a treatment for people with cancer have already been conducted.[2,3,4,6,7,8,9,15,16,17,18,49,50] Additional clinical studies, MDA-ID-99303 and AETERNA-AE-MM-00-02 have been completed.[6,15,50]

The absence of blood vessels in cartilage led to the hypothesis that cartilage cells (also known as chondrocytes) produce one or more substances that inhibit blood vessel formation.[27,28,29,30,35,36,48] The formation of new blood vessels or angiogenesis is necessary for tumors to grow larger than a few millimeters in diameter (i.e., larger than approximately 100,000 to 1,000,000 cells) because tumors, like normal tissues, must obtain most of their oxygen and nutrients from blood.[33,34,41,51,52,53,54] A developing tumor, therefore, cannot continue to grow unless it establishes connections to the circulatory system of its host. It has been reported that tumors can initiate the process of angiogenesis when they contain as few as 100 cells.[53] Inhibition of angiogenesis at this early stage may, in some instances, lead to complete tumor regression.[53] The possibility that cartilage could be a source of one or more types of angiogenesis inhibitors for the treatment of cancer has prompted much research.


The major structural components of cartilage include several types of the protein collagen and several types of glycosaminoglycans, which are polysaccharides.[19,29,30,39,48,54,55]Chondroitin sulfate is the major glycosaminoglycan in cartilage.[39,54] Although there is no evidence that the collagens in cartilage, or their breakdown products, can inhibit angiogenesis, there is evidence that shark cartilage contains at least one angiogenesis inhibitor that has a glycosaminoglycan component (refer to the Laboratory/Animal/Preclinical Studies section of this summary for more information).[46] Other data indicate that most of the antiangiogenic activity in cartilage is not associated with the major structural components.[26,30,48]

Some glycosaminoglycans in cartilage reportedly have anti-inflammatory and immune-system -stimulating properties,[1,2,14,16,56,57] and it has been suggested that either they or some of their breakdown products are toxic to tumor cells.[2,3,24] Thus, the antitumor potential of cartilage may involve more than one mechanism of action.

Cartilage products are sold commercially in the United States as dietary supplements. More than 40 different brand names of shark cartilage alone are available to consumers.[17] In the United States, dietary supplements are regulated as foods, not drugs. Therefore, premarket evaluation and approval by the U.S. Food and Drug Administration (FDA) are not required unless specific disease prevention or treatment claims are made. Because manufacturers of cartilage products are not required to show evidence of anticancer or other biologic effects, it is unclear whether any of these products have therapeutic potential. In addition, individual products may vary considerably from lot to lot because standard manufacturing processes do not exist, and binding agents and fillers may be added during production.[17] The FDA has not approved the use of cartilage as a treatment for people with cancer or any other medical condition. The FDA is notifying consumers of a refund program for purchasers of Lane Labs-USA, Inc.'s shark cartilage product, BeneFin. Consumers are eligible for a partial refund of the purchase price and any shipping and handling costs if this product was purchased between September 22, 1999 and July 12, 2004.


To conduct clinical drug research in the United States, researchers must file an Investigational New Drug (IND) application with the FDA. To date, IND status has been granted to at least four groups of investigators, one of which was the MDA-ID-99303 trial, that is now closed, to study cartilage as a treatment for people with cancer.[7,18,58] Because the IND application process is confidential and because the existence of an IND can be disclosed only by the applicants, it is not known whether other applications have been made.

In animal studies, cartilage products have been administered in a variety of ways. In some studies, oral administration of either liquid or powdered forms has been used.[19,39,40,43,44,59,15,47] In other studies, cartilage products have been given by injection (intravenous or intraperitoneal), applied topically, or placed in slow-release plastic pellets that were surgically implanted.[26,27,28,32,33,35,38,40,42,44,46,48] Most of the latter studies investigated the effects of cartilage products on the development of blood vessels in the chorioallantoic membrane of chicken embryos, the cornea of rabbits, or the conjunctiva of mice.[26,27,28,32,35,38,40,42,44,46,48]

In human studies (MDA-ID-99303, AETERNA-AE-MM-00-02, and NCCTG-971151), cartilage products have been administered topically or orally, or they have been given by enema or subcutaneous injection.[2,3,4,7,8,9]AETERNA-AE-RC-99-02,[6,15,16,18,60] For oral administration, liquid, powdered, and pill forms have been used as described in the following closed trials, MDA-ID-99303, NCCTG-971151, and AETERNA-AE-MM-00-02.[2,3,4,6,7,8,9,15,16,18] The dose and duration of cartilage treatment have varied in human studies, in part because different types of products have been tested.

In this summary, the brand name (i.e., registered or trademarked name) of the cartilage product(s) used in individual studies will be identified wherever possible.


  1. 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.
  2. Prudden JF: The treatment of human cancer with agents prepared from bovine cartilage. J Biol Response Mod 4 (6): 551-84, 1985.
  3. 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.
  4. Puccio C, Mittelman A, Chun P, et al.: Treatment of metastatic renal cell carcinoma with Catrix. [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-769, 246, 1994.
  5. Dupont E, Savard PE, Jourdain C, et al.: Antiangiogenic properties of a novel shark cartilage extract: potential role in the treatment of psoriasis. J Cutan Med Surg 2 (3): 146-52, 1998.
  6. Falardeau P, Champagne P, Poyet P, et al.: Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials. Semin Oncol 28 (6): 620-5, 2001.
  7. 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.
  8. Leitner SP, Rothkopf MM, Haverstick L, et al.: Two phase II studies of oral dry shark cartilage powder (SCP) with either metastatic breast or prostate cancer refractory to standard treatment. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A-240, 1998.
  9. Rosenbluth RJ, Jennis AA, Cantwell S, et al.: Oral shark cartilage in the treatment of patients with advanced primary brain tumors. [Abstract] Proceedings of the American Society of Clinical Oncology 18: A-554, 1999.
  10. Iandoli R: Shark cartilage in the treatment of psoriasis. Dermatologia Clinica 21 (part 1): 39-42, 2001.
  11. Milner M: A guide to the use of shark cartilage in the treatment of arthritis and other inflammatory joint diseases. American Chiropractor 21 (4): 40-2, 1999.
  12. Himmel PB, Seligman TM: Treatment of systemic sclerosis with shark cartilage extract. Journal of Orthomolecular Medicine 14 (2): 73-7, 1999. Also available online. Last accessed January 23, 2014.
  13. Sorbera LA, Castañer RM, Leeson PA: AE-941. Oncolytic, antipsoriatic, treatment of age-related macular degeneration, angiogenesis inhibitor. Drugs Future 25 (6): 551-7, 2000.
  14. 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.
  15. AE 941--Neovastat. Drugs R D 1 (2): 135-6, 1999.
  16. 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.
  17. Holt S: Shark cartilage and nutriceutical update. Altern Complement Ther 1 (6): 414-16, 1995.
  18. Hunt TJ, Connelly JF: Shark cartilage for cancer treatment. Am J Health Syst Pharm 52 (16): 1756, 1760, 1995.
  19. 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.
  20. Ostrander GK, Cheng KC, Wolf JC, et al.: Shark cartilage, cancer and the growing threat of pseudoscience. Cancer Res 64 (23): 8485-91, 2004.
  21. Finkelstein JB: Sharks do get cancer: few surprises in cartilage research. J Natl Cancer Inst 97 (21): 1562-3, 2005.
  22. Schlumberger HG, Lucke B: Tumors of fishes, amphibians, and reptiles. Cancer Res 8 (12): 657-754, 1948.
  23. Wellings SR: Neoplasia and primitive vertebrate phylogeny: echinoderms, prevertebrates, and fishes--A review. Natl Cancer Inst Monogr 31: 59-128, 1969.
  24. 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.
  25. 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.
  26. Moses MA, Sudhalter J, Langer R: Identification of an inhibitor of neovascularization from cartilage. Science 248 (4961): 1408-10, 1990.
  27. Moses MA, Sudhalter J, Langer R: Isolation and characterization of an inhibitor of neovascularization from scapular chondrocytes. J Cell Biol 119 (2): 475-82, 1992.
  28. Moses MA: A cartilage-derived inhibitor of neovascularization and metalloproteinases. Clin Exp Rheumatol 11 (Suppl 8): S67-9, 1993 Mar-Apr.
  29. 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.
  30. 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.
  31. Sadove AM, Kuettner KE: Inhibition of mammary carcinoma invasiveness with cartilage-derived inhibitor. Surg Forum 28: 499-501, 1977.
  32. Langer R, Brem H, Falterman K, et al.: Isolations of a cartilage factor that inhibits tumor neovascularization. Science 193 (4247): 70-2, 1976.
  33. Langer R, Conn H, Vacanti J, et al.: Control of tumor growth in animals by infusion of an angiogenesis inhibitor. Proc Natl Acad Sci U S A 77 (7): 4331-5, 1980.
  34. 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.
  35. 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.
  36. Hiraki Y, Inoue H, Iyama K, et al.: Identification of chondromodulin I as a novel endothelial cell growth inhibitor. Purification and its localization in the avascular zone of epiphyseal cartilage. J Biol Chem 272 (51): 32419-26, 1997.
  37. 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.
  38. Lee A, Langer R: Shark cartilage contains inhibitors of tumor angiogenesis. Science 221 (4616): 1185-7, 1983.
  39. Davis PF, He Y, Furneaux RH, et al.: Inhibition of angiogenesis by oral ingestion of powdered shark cartilage in a rat model. Microvasc Res 54 (2): 178-82, 1997.
  40. Sheu JR, Fu CC, Tsai ML, et al.: Effect of U-995, a potent shark cartilage-derived angiogenesis inhibitor, on anti-angiogenesis and anti-tumor activities. Anticancer Res 18 (6A): 4435-41, 1998 Nov-Dec.
  41. McGuire TR, Kazakoff PW, Hoie EB, et al.: Antiproliferative activity of shark cartilage with and without tumor necrosis factor-alpha in human umbilical vein endothelium. Pharmacotherapy 16 (2): 237-44, 1996 Mar-Apr.
  42. Oikawa T, Ashino-Fuse H, Shimamura M, et al.: A novel angiogenic inhibitor derived from Japanese shark cartilage (I). Extraction and estimation of inhibitory activities toward tumor and embryonic angiogenesis. Cancer Lett 51 (3): 181-6, 1990.
  43. Morris GM, Coderre JA, Micca PL, et al.: Boron neutron capture therapy of the rat 9L gliosarcoma: evaluation of the effects of shark cartilage. Br J Radiol 73 (868): 429-34, 2000.
  44. Dupont E, Falardeau P, Mousa SA, et al.: Antiangiogenic and antimetastatic properties of Neovastat (AE-941), an orally active extract derived from cartilage tissue. Clin Exp Metastasis 19 (2): 145-53, 2002.
  45. Béliveau R, Gingras D, Kruger EA, et al.: The antiangiogenic agent neovastat (AE-941) inhibits vascular endothelial growth factor-mediated biological effects. Clin Cancer Res 8 (4): 1242-50, 2002.
  46. Liang JH, Wong KP: The characterization of angiogenesis inhibitor from shark cartilage. Adv Exp Med Biol 476: 209-23, 2000.
  47. Wojtowicz-Praga S: Clinical potential of matrix metalloprotease inhibitors. Drugs R D 1 (2): 117-29, 1999.
  48. Suzuki F: Cartilage-derived growth factor and antitumor factor: past, present, and future studies. Biochem Biophys Res Commun 259 (1): 1-7, 1999.
  49. Batist G, Champagne P, Hariton C, et al.: Dose-survival relationship in a phase II study of Neovastat in refractory renal cell carcinoma patients. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1907, 2002.
  50. Loprinzi CL, Levitt R, Barton DL, et al.: Evaluation of shark cartilage in patients with advanced cancer: a North Central Cancer Treatment Group trial. Cancer 104 (1): 176-82, 2005.
  51. Folkman J: The role of angiogenesis in tumor growth. Semin Cancer Biol 3 (2): 65-71, 1992.
  52. Sipos EP, Tamargo RJ, Weingart JD, et al.: Inhibition of tumor angiogenesis. Ann N Y Acad Sci 732: 263-72, 1994.
  53. 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.
  54. Alberts B, Bray D, Lewis J, et al.: Molecular Biology of the Cell. 3rd ed. New York, NY: Garland Publishing, 1994.
  55. Cremer MA, Rosloniec EF, Kang AH: The cartilage collagens: a review of their structure, organization, and role in the pathogenesis of experimental arthritis in animals and in human rheumatic disease. J Mol Med 76 (3-4): 275-88, 1998.
  56. Rosen J, Sherman WT, Prudden JF, et al.: Immunoregulatory effects of catrix. J Biol Response Mod 7 (5): 498-512, 1988.
  57. 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.
  58. Simone CB, Simone NL, Simone CB 2nd: Shark cartilage for cancer. Lancet 351 (9113): 1440, 1998.
  59. Horsman MR, Alsner J, Overgaard J: The effect of shark cartilage extracts on the growth and metastatic spread of the SCCVII carcinoma. Acta Oncol 37 (5): 441-5, 1998.
  60. Gingras D, Batist G, Béliveau R: AE-941 (Neovastat): a novel multifunctional antiangiogenic compound. Expert Rev Anticancer Ther 1 (3): 341-7, 2001.
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