Cancer cachexia: mediating factors and the effect of eicosapentaenoic acid dieting
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Department of Immunology, Nicolaus Copernicus University, Torun, Poland
Małgorzata Kowalczewska   

Institute of General and Molecular Biology, Department of Immunology, Nicolaus Copernicus University, Torun, Poland.
J Pre Clin Clin Res. 2010;4(2):108–111
Cancer cachexia is an involuntary weight loss of more than 10% of premorbid weight, caused by depletion of lipid stores, muscle wasting, anorexia and metabolic alterations. It results from a complex tumour-host interaction associated with an elevated production of cytokines (e.g. TNF-α, IL-1, IL-6) and release of tumour-derived catabolic factors (e.g. lipid-mobilizing factor, protein-mobilizing factor). In this paper we discuss data suggesting a potential role of ω-3 fatty acids, such as eicosapentaenoic acid (EPA) in the treatment of cancer cachexia. These data indicate that dieting EPA decreases production of cytokines, attenuates the lipolysis process and reduces activity of the proteolysis-inducing factor (PIF). In contrast to other therapeutic agents, which only improve appetite, it has been shown that EPA supplementation prolonged the survival of cancer cachexia patients.
Inui A: Cancer anorexia-cachexia syndrome. CA Cancer J Clin 2002, 52, 72-91.
Argilés JM, López-Soriano FJ, Busquets S: Cancer anorexia-cachexia syndrome. Drug Discov Today 2008, 13, 73-78.
Argilés JM, Moore-Carrasco R, Fuster G, Busquets S, López-Soriano FJ: Cancer cachexia: the molecular mechanisms. Int J Biochem Cell Biol 2003, 35, 405-409.
Davis PM, Dickerson D: Cachexia and anorexia: cancer’s covert killer. Support Care Cancer 2000, 8, 180-187.
Matthys P, Billiau A: Cytokines and cachexia. Nutrition 1997, 13, 763-770.
Giacosa A, Rondanelli M: Fish oil and treatment of cancer cachexia. Genes Nutr 2008, 3, 25-28.
Bosaeus I: Nutritional support in multimodal therapy for cancer cachexia. Support Care Cancer 2008, 16, 447-451.
Tisdale MJ: Inhibition of lipolysis and muscle protein degradation by EPA in cancer cachexia. Nutrition 1996, 12, 31-33.
Skipworth RJ, Dejong CH, Preston T, Fearon KC: Pathophysiology of cancer cachexia: much more than host-tumour interaction? Clin Nutr 2007, 26(6), 667-676.
Jakóbisiak M: Immunologia, wyd. II (in Polish). Immunology, Ed. II. Wydawnictwo Naukowe PWN, Warsaw 1996, 233-238.
Tisdale MJ: Cancer cachexia: metabolic alterations and clinical manifestations. Nutrition 1997, 13, 1-7.
Buck M, Chojkier M: Muscle wasting and dedifferentiation induced by oxidative stress in a murine model of cachexia is prevented by inhibitors of nitric oxide synthesis and antioxidants. EMBO J 1996, 15, 1753- 1765.
Kozak W, Kluger MJ, Soszyński D, Conn CA, Rudolph K, Leon LR, Zheng H: IL-6 and IL-1β in fever: Studies using cytokine-deficient (knockout) mice. Ann N Y Acad Sci 1998, 856, 33-47.
Dinarello CA: Interleukin 1 as mediator of the acute-phase response. Surv Immunol Res 1984, 3, 29-33.
Strassmann G, Fong M, Kenney JS, Jacob CO: Evidence for the involvement of interleukin 6 in experimental cancer cachexia. J Clin Invest 1992, 89, 1681.
Strassmann G, Jacob CO, Evans R, Beall D, Fong M: Mechanisms of experimental cancer cahcexia. Interaction between mononuclear phagocytes and colon-26 carcinoma and its relevance to IL-6 mediated cancer cachexia. J Immunol 1992, 148, 3674.
Metcalf D, Gearing DP: Fatal syndrome in mice engrafted with cells producing high levels of the leukemia inhibitory factor. Proc Natl Acad Sci USA 1989, 86, 5948.
Matthys P, Dijkmans R, P. Proost P, Van Damme J, Heremans H, Sobis H, Billiau A: Severe cachexia in mice inoculated with interferon-γ- producing tumor cells. Int J Cancer 1991, 49, 77-82.
Argilés JM, Busquets S, García-Martínez Cet, López-Soriano FJ: Mediators involved in the cancer anorexia-cachexia syndrome: past, present and future. Nutrition 2005, 21, 977-985.
Sanders PM, Tisdale MJ: Role of lipid-mobilising factor (LMF) in protecting tumour cells from oxidative damage. Br J Cancer 2004, 90(6), 1274-1278.
Shing-Shing, Y, Blackwood K, Schuster MW: The cytokine basis of cachexia and its treatment: Are they ready for prime time? J Am Med Dir Assoc 2008, 23.
Lorite, MJ, Thompson MG, Drake JL, Carling G, Tisdale MJ: Mechanism of muscle protein degradation induced by a cancer cachectic factor. Br J Cancer 1998, 78(7), 850-856.
Whitehouse AS, Tisdale MJ: Increased expression of the ubiquitin proteasome pathway in murine myotubes by proteolysis-inducing factor (PIF) is associated with activation of the transcription factor NFkappaB. Br J Cancer 2003, 89(6),1116-1122
Ross JA, Fearon KC: Eicosanoid-dependent cancer cachexia and wasting. Curr Opin Clin Nutr Metab Care 2002, 5(3), 241-248.
Cook ME: Regulation of eicosanoid pathways: a pathway to health and development. Pakistan J Nutr 2002, 1(2), 103-105.
MacDonald N, Easson AM, Mazurak VC, Dunn GP, Baracos VE: Understanding and managing cancer cachexia. J Am Coll Surg 2003, 197(1), 143-161.
Wang D, DuBois RN: Eicosanoids and cancer. Nat Rev 2010, 10, 181- 193.
Harris RE: Cyclooxygenase-2 (cox-2) blockade in the chemoprevention of cancers of the coclon, breast, prostate, and lung. Inflammopharmacology 2009, 17, 55-67.
Roe SY, Cooper AL, Morris ID, Rothwell NJ: Involvement of prostaglandins in cachexia induced by T-cell leukemia in the rat. Metabolism 1997, 46(4), 359-365.
Senior K: Why is progress in treatment of cancer cachexia so slow? J Exp Med 2007, 8, 671-672.
Karmali RA: Historical perspective and potential use of n-3 fatty acids in therapy of cancer cachexia. Nutrition 1996, 12, 2-4.
Stehr SN, Heller AR: Omega-3 fatty acid effects on biochemical indices following cancer surgery. Clin Chim Acta 2006, 373, 1-8.
Kozak, WD, Soszyński D, Rudolph K, Conn CA, Kluger MJ: Dietary n-3 fatty acids differentially affect sickness behavior in mice during local and systemic inflammation. Am J Physiol 1997, 272, 1298-1307.
Barber MD: Cancer cachexia and its treatment with fish-oil-enriched nutritional supplementation. Nutrition 2001, 17, 751-755.
Babcock TS, Helton S, Espat NJ: Eicosapentaenoic Acid (EPA): An Antiinflammatory ω-3 Fat With Potential Clinical Applications. Nutrition 2000, 16, 1116-1118.
Jatoi A: Fish oil, lean tissue, and cancer: is there a role for eicosapentaenoic acid in treating the cancer anorexia/weight loss syndrome? Crit Rev Oncol Hematol 2005, 55, 37-43.
Baracos VE, DeVivo C, Hoyle DH, Goldberg AL: Activation of the ATP-ubiquitin-proteasome pathway in skeletal muscle of cachectic rats bearing a hepatoma. Am J Physiol 1995, 268, 996-1006.
Whitehouse AS, Smith HJ, Drake JL, Tisdae MJ: Mechanism of attenuation of skeletal muscle protein catabolism in cancer cachexia by eicosapentaenoic acid. Cancer Res 2001, 61, 3604-3609.
Smith HJ, Greenberg NA, Tisdale MJ: Effect of eicosapentaenoic acid, protein and amino acids on protein synthesis and degradation in skeletal muscle of cachectic mice. Br J Cancer 2004, 91, 408-412.
Price SA, Tisdale MJ: Mechanism of inhibition of a tumor lipid mobilizing factor by eicosapentaenoic acid. Cancer Res 1998, 21, 4827- 4831.