The therapeutic potential of cartilage has been investigated for more than 30 years. As noted previously (refer to the General Information ¹ section of this summary for more information), cartilage products have been tested as treatments for cancer, psoriasis, and arthritis. Cartilage products have also been studied as enhancers of wound repair and as treatments for osteoporosis, ulcerative colitis, regional enteritis, acne, scleroderma, hemorrhoids, severe anal itching, and the dermatitis caused by poison oak and poison ivy.[1] Reviewed in [2-5]

Early studies of cartilage’s therapeutic potential utilized extracts of bovine (cow) cartilage. The ability of these extracts to suppress inflammation was first described in the early 1960s.[1] The first report that bovine cartilage contains at least one angiogenesis inhibitor was published in the mid-1970s.[6] The use of bovine cartilage extracts to treat patients with cancer and the ability of these extracts to kill cancer cells directly and to stimulate animal immune systems were first described in the mid- to late-1980s.[7-10]

The first report that shark cartilage contains at least one angiogenesis inhibitor was published in the early 1980s,[11] and the only published report to date of a clinical trial of shark cartilage as a treatment for cancer appeared in the late 1990s.[12] The more recent interest in shark cartilage is due, in part, to the greater abundance of cartilage in this animal and its apparently higher level of antiangiogenic activity. Approximately 6% of the body weight of a shark is composed of cartilage, compared with less than 1% of the body weight of a cow. Reviewed in [13] In addition, on a weight-for-weight basis, shark cartilage contains approximately 1,000 times more antiangiogenic activity than bovine cartilage.[11] Reviewed in [14]

As indicated previously (refer to the Overview ² and General Information ¹ sections of this summary for more information), at least three different mechanisms of action have been proposed to explain the anticancer potential of cartilage: 1) it is toxic to cancer cells; 2) it stimulates the immune system; and 3) it inhibits angiogenesis. Only limited evidence is available to support the first two mechanisms of action; however, the evidence in favor of the third mechanism is more substantial (refer to the Laboratory/Animal/Preclinical Studies ³ section of this summary for more information).

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. Reviewed in [15-19] Second, the activated endothelial cells must divide to produce new endothelial cells, which will be used to make the new blood vessels. Reviewed in [16,18-21] Third, the dividing endothelial cells must migrate toward the tumor. Reviewed in [16-21] 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. Reviewed in [19-23] Fourth, the new endothelial cells must form the hollow tubes that will become the new blood vessels. Reviewed in [18,19] Some angiogenesis inhibitors may be able to block more than one step in this process.

Cartilage is relatively resistant to invasion by tumor cells, Reviewed in [24-31] and tumor cells use matrix metalloproteinases when they migrate during the process of metastasis. Reviewed in [14,22,26,32,33] 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.[34-36] Reviewed in [37]

Learn more about angiogenesis ⁴.

References

1. Houck JC, Jacob RA, DeAngelo L, et al.: The inhibition of inflammation and the acceleration of tissue repair by cartilage powder. Surgery 51: 632-38, 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.  [PUBMED Abstract]
   
   
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.  [PUBMED Abstract]
   
   
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.  [PUBMED Abstract]
   
   
6. Langer R, Brem H, Falterman K, et al.: Isolations of a cartilage factor that inhibits tumor neovascularization. Science 193 (4247): 70-2, 1976.  [PUBMED Abstract]
   
   
7. Prudden JF: The treatment of human cancer with agents prepared from bovine cartilage. J Biol Response Mod 4 (6): 551-84, 1985.  [PUBMED Abstract]
   
   
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.  [PUBMED Abstract]
   
   
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.  [PUBMED Abstract]
   
   
10. Rosen J, Sherman WT, Prudden JF, et al.: Immunoregulatory effects of catrix. J Biol Response Mod 7 (5): 498-512, 1988.  [PUBMED Abstract]
    
    
11. Lee A, Langer R: Shark cartilage contains inhibitors of tumor angiogenesis. Science 221 (4616): 1185-7, 1983.  [PUBMED Abstract]
    
    
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.  [PUBMED Abstract]
    
    
13. Hunt TJ, Connelly JF: Shark cartilage for cancer treatment. Am J Health Syst Pharm 52 (16): 1756, 1760, 1995.  [PUBMED Abstract]
    
    
14. Reviews of Therapies: Biologic/Organic/Pharmacologic Therapies: Cartilage. Houston, Tex: M.D. Anderson Cancer Center, 2003. Available online. ⁵ Last accessed September 16, 2009. 
    
    
15. Folkman J: The role of angiogenesis in tumor growth. Semin Cancer Biol 3 (2): 65-71, 1992.  [PUBMED Abstract]
    
    
16. Sipos EP, Tamargo RJ, Weingart JD, et al.: Inhibition of tumor angiogenesis. Ann N Y Acad Sci 732: 263-72, 1994.  [PUBMED Abstract]
    
    
17. 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.  [PUBMED Abstract]
    
    
18. Alberts B, Bray D, Lewis J, et al.: Molecular Biology of the Cell. 3rd ed. New York, NY: Garland Publishing, 1994. 
    
    
19. Moses MA: The regulation of neovascularization of matrix metalloproteinases and their inhibitors. Stem Cells 15 (3): 180-9, 1997.  [PUBMED Abstract]
    
    
20. Stetler-Stevenson WG: Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention. J Clin Invest 103 (9): 1237-41, 1999.  [PUBMED Abstract]
    
    
21. 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.  [PUBMED Abstract]
    
    
22. McCawley LJ, Matrisian LM: Matrix metalloproteinases: multifunctional contributors to tumor progression. Mol Med Today 6 (4): 149-56, 2000.  [PUBMED Abstract]
    
    
23. Mandal M, Mandal A, Das S, et al.: Clinical implications of matrix metalloproteinases. Mol Cell Biochem 252 (1-2): 305-29, 2003.  [PUBMED Abstract]
    
    
24. 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.  [PUBMED Abstract]
    
    
25. 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.  [PUBMED Abstract]
    
    
26. Sadove AM, Kuettner KE: Inhibition of mammary carcinoma invasiveness with cartilage-derived inhibitor. Surg Forum 28: 499-501, 1977.  [PUBMED Abstract]
    
    
27. 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.  [PUBMED Abstract]
    
    
28. 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.  [PUBMED Abstract]
    
    
29. 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.  [PUBMED Abstract]
    
    
30. Liang JH, Wong KP: The characterization of angiogenesis inhibitor from shark cartilage. Adv Exp Med Biol 476: 209-23, 2000.  [PUBMED Abstract]
    
    
31. Suzuki F: Cartilage-derived growth factor and antitumor factor: past, present, and future studies. Biochem Biophys Res Commun 259 (1): 1-7, 1999.  [PUBMED Abstract]
    
    
32. 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.  [PUBMED Abstract]
    
    
33. Wojtowicz-Praga S: Clinical potential of matrix metalloprotease inhibitors. Drugs R D 1 (2): 117-29, 1999.  [PUBMED Abstract]
    
    
34. 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.  [PUBMED Abstract]
    
    
35. Sigel MM, Fugmann RA: Studies on immunoglobulins reactive with tumor cells and antigens. Cancer Res 28 (7): 1457-9, 1968.  [PUBMED Abstract]
    
    
36. 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.  [PUBMED Abstract]
    
    
37. Pugliese PT, Heinerman J: Devour Disease with Shark Liver Oil. Green Bay, Wis: Impakt Communications, 1999. 
    
    

Glossary Terms

A disorder of the skin in which oil glands and hair glands become inflamed.

Having to do with the anus. The anus is the opening of the rectum (last part of the large intestine) to the outside of the body.

Blood vessel formation. Tumor angiogenesis is the growth of new blood vessels that tumors need to grow. This is caused by the release of chemicals by the tumor.

A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor may prevent the growth of new blood vessels that tumors need to grow.

Having to do with reducing the growth of new blood vessels.

Having to do with stopping abnormal cell growth.

A disease that causes inflammation and pain in the joints.

A tube through which the blood circulates in the body. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins.

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

A tough, flexible tissue that lines joints and gives structure to the nose, ears, larynx, and other parts of the body.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical trial.

Inflammation of the skin.

The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart.

A protein that speeds up chemical reactions in the body.

An enlarged or swollen blood vessel, usually located near the anus or the rectum.

The complex group of organs and cells that defends the body against infections and other diseases.

Redness, swelling, pain, and/or a feeling of heat in an area of the body. This is a protective reaction to injury, disease, or irritation of the tissues.

A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis.

The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-tuh-SEEZ).

The smallest particle of a substance that has all of the physical and chemical properties of that substance. Molecules are made up of one or more atoms. If they contain more than one atom, the atoms can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms.

A condition that is marked by a decrease in bone mass and density, causing bones to become fragile.

A chronic disease of the skin marked by red patches covered with white scales.

Chronic inflammation of the gastrointestinal tract, most commonly the small intestine and colon. Regional enteritis increases the risk for colorectal cancer and small intestine cancer. Also called Crohn disease.

A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic).

Having to do with treating disease and helping healing take place.

Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects.

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.

Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel.

A substance made by cells that stimulates new blood vessel formation. Also called VEGF.

A break in the skin or other body tissues caused by injury or surgical incision (cut).