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n-3 Polyunsaturated fatty acids throughout the cancer trajectory: influence on disease incidence, progression, response to therapy and cancer-associated cachexia

Published online by Cambridge University Press:  14 December 2007

Vickie E. Baracos ,
Vera C. Mazurak  and
David W. L. Ma
Vickie E. Baracos*
Affiliation:
Department of Oncology, Division of Palliative Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2P5
Vera C. Mazurak
Affiliation:
Department of Oncology, Division of Palliative Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2P5
David W. L. Ma
Affiliation:
Faculty of Nutrition, Texas A&M University, College Station, Texas, USA
*
*Corresponding author: Dr Vickie E. Baracos, fax +1 780 432 8425, email [email protected]
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Abstract

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Evidence from epidemiological studies suggests that diets rich in n-3 PUFA may be associated with reduced cancer risk. These observations have formed the rationale for exploring the mechanisms by which n-3 PUFA may be chemoprotective and have resulted in significant advances in our mechanistic understanding of n-3 PUFA action on tumour growth. Various interrelated and integrated mechanisms may be at work by which n-3 PUFA influence cancer at all stages of initiation, promotion, progression, and neoplastic transformation. More recently, experimental studies have reported enhanced tumour cell death with chemotherapy when fish oil is provided while toxic side effects to the host are reduced. Furthermore, cancer-associated wasting has been shown to be attenuated by fish oil supplementation. Clinical evidence suggests that the n-3 PUFA status of newly diagnosed cancer patients and individuals undergoing chemotherapy is low. Therefore, both the disease itself and therapeutic treatments may be contributing factors in the decline of n-3 PUFA status. Dietary supplementation to maintain and replenish n-3 PUFA status at key points in the cancer disease trajectory may provide additional health benefits and an enhanced quality of life. The present review will focus on and critically examine current research efforts related to the putative anti-cancer effects of n-3 PUFA and their suggested ability to palliate cancer-associated and treatment-associated symptoms.

Keywords

CancerPolyunsaturated fatty acidsFish oilChemotherapyCachexiaDrug resistance
Type
research-article
Information
Nutrition Research Reviews , Volume 17 , Issue 2 , December 2004 , pp. 177 - 192
Copyright
Copyright © The Authors 2004

References

Abulrob, ANG, Mason, M, Bryce, R & Gumbleton, M (2000) The effect of fatty acids and analogues upon intracellular levels of doxorubicin in cells displaying P-glycoprotein mediated multidrug resistance. Journal of Drug Targeting 8, 247–256.CrossRefGoogle ScholarPubMed
Amano, H, Hayashi, I, Endo, H, Kitasato, H, Yamashina, S, Maruyama, T, Kobayashi, M, Satoh, K, Narita, M, Sugimoto, Y, Murata, T, Yoshimura, H, Narumiya, S & Majima, M (2003) Host prostaglandin E(2)-EP3 signaling regulates tumor-associated angiogenesis and tumor growth. Journal of Experimental Medicine 197, 221–232.CrossRefGoogle ScholarPubMed
Amiano, P, Dorronsoro, M, Larranaga, N, Renobales, M & Ruiz de Gordoa, JC (2002) Very-long-chain omega-3 fatty acids as markers for habitual fish intake in Spain. IARC Scientific Publications 156, 201–202.Google ScholarPubMed
Arancia, G, Molinari, A, Calcabrini, A, Meschini, S & Cianfriglia, M (2001) Intracellular P-glycoprotein in multidrug resistant tumor cells. Italian Journal of Anatomy and Embryology 106, 59–68.Google ScholarPubMed
Argiles, JM, Alvarez, B, Carbo, N, Busquets, S, van Royen, M & Lopez-Soriano, FJ (2000) The divergent effects of tumour necrosis factor-alpha on skeletal muscle: implications in wasting. European Cytokine Network 11, 552–559.Google ScholarPubMed
Argiles, JM & Lopez-Soriano, FJ (1999) The role of cytokines in cancer cachexia. Medical Research Reviews 19, 223–248.3.0.CO;2-N>CrossRefGoogle ScholarPubMed
Augustsson, K, Michaud, DS, Rimm, EB, Leitzmann, MF, Stampfer, MJ, Willett, WC & Giovannucci, E (2003) A prospective study of intake of fish and marine fatty acids and prostate cancer. Cancer Epidemiology, Biomarkers and Prevention 12, 64–67.Google ScholarPubMed
Badawi, AF & Badr, MZ (2003) Expression of cyclooxygenase-2 and peroxisome proliferator-activated receptor-gamma and levels of prostaglandin E2 and 15-deoxy-delta12,14-prostaglandin J2 in human breast cancer and metastasis. International Journal of Cancer 103, 84–90.CrossRefGoogle Scholar
Baracos, VE (2000) A panoply of anabolic and catabolic mediators. Current Opinion in Clinical Nutrition and Metabolic Care 3, 169–170.CrossRefGoogle ScholarPubMed
Baracos, VE (2001) A deadly combination of anorexia and hypermetabolism. Current Opinion in Clinical Nutrition and Metabolic Care 4, 175–177.CrossRefGoogle ScholarPubMed
Barber, MD, Fearon, KC, Tisdale, MJ, McMillan, DC & Ross, JA (2001) Effect of a fish oil-enriched nutritional supplement on metabolic mediators in patients with pancreatic cancer cachexia. Nutrition and Cancer 40, 118–124.CrossRefGoogle ScholarPubMed
Barber, MD & Fearon, KCH (2001) Tolerance and incorporation of a high-dose eicosapentaenoic acid diester emulsion by patients with pancreatic cancer cachexia. Lipids 36, 347–351.CrossRefGoogle ScholarPubMed
Barber, MD, Ross, JA & Fearon, KC (2000) Disordered metabolic response with cancer and its management. World Journal of Surgery 24, 681–689.CrossRefGoogle ScholarPubMed
Barber, MD, Ross, JA, Preston, T, Shenkin, A & Fearon, KC (1999 a) Fish oil-enriched nutritional supplement attenuates progression of the acute-phase response in weight-losing patients with advanced pancreatic cancer. Journal of Nutrition 129, 1120–1125.CrossRefGoogle ScholarPubMed
Barber, MD, Ross, JA, Voss, AC, Tisdale, MJ & Fearon, KC (1999 b) The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer. British Journal of Cancer 81, 80–86.CrossRefGoogle ScholarPubMed
Bartsch, H, Nair, J & Owen, RW (1999) Dietary polyunsaturated fatty acids and cancers of the breast and colorectum: emerging evidence for their role as risk modifiers. Carcinogenesis 20, 2209–2218.CrossRefGoogle ScholarPubMed
Batist, G, Tulpule, A, Sinha, BK, Katki, AG, Myers, CE & Cowan, KH (1986) Overexpression of a novel anionic glutathione transferase in multidrug-resistant human breast cancer cells. Journal of Biological Chemistry 261, 15544–15549.CrossRefGoogle ScholarPubMed
Birkenkamp-Demtroder, K, Christensen, LL, Olesen, SH, Frederiksen, CM, Laiho, P, Aaltonen, LA, Laurberg, S, Sorensen, FB, Hagemann, R & Orntoft, TF (2002) Gene expression in colorectal cancer. Cancer Research 62, 4352–4363.Google ScholarPubMed
Black, HS, Thornby, JI, Gerguis, J & Lenger, W (1992) Influence of dietary omega-6,-3 fatty acid sources on the initiation and promotion stages of photocarcinogenesis. Photochemistry and Photobiology 56, 195–199.CrossRefGoogle ScholarPubMed
Bordoni, A, Biagi, PL & Hrelia, S (1999) The impairment of essential fatty acid metabolism as a key factor in doxorubicin-induced damage in cultured rat cardiomyocytes. Biochimica et Biophysica Acta 1440, 100–106.CrossRefGoogle ScholarPubMed
Bougnoux, P (1999) n-3 Polyunsaturated fatty acids and cancer. Current Opinion in Clinical Nutrition and Metabolic Care 2, 121–126.CrossRefGoogle ScholarPubMed
Bradley, MO, Webb, NL, Anthony, FH, Devanesan, P, Witman, PA, Hemamalini, S, Chander, MC, Baker, SD, He, LF, Horwitz, SB & Swindell, CS (2001) Tumor targeting by covalent conjugation of a natural fatty acid to paclitaxel. Clinical Cancer Research 7, 3229–3238.Google ScholarPubMed
Bruera, E, Strasser, F, Palmer, JL, Willey, J, Calder, K, Amyotte, G & Baracos, VE (2003) Effect of fish oil on appetite and other symptoms in patients with advanced cancer and anorexia/cachexia: a double blind, placebo-controlled trial. Journal of Clinical Oncology 21, 129–134.CrossRefGoogle Scholar
Burns, CP, Halabi, S, Clamon, GH, Hars, V, Wagner, BA, Hohl, RJ, Lester, E, Kirshner, JJ, Vinciguerra, V & Paskett, E (1999) Phase I clinical study of fish oil fatty acid capsules for patients with cancer cachexia: cancer and leukemia group B study 9473. Clinical Cancer Research 5, 3942–3947.Google Scholar
Cabal-Manzano, R, Bhargava, P, Torres-Duarte, A, Marshall, J, Bhargava, P & Wainer, IW (2001) Proteolysis-inducing factor is expressed in tumours of patients with gastrointestinal cancers and correlates with weight loss. British Journal of Cancer 84, 1599–1601.CrossRefGoogle ScholarPubMed
Cahlin, C, Gelin, J, Delbro, D, Lonnroth, C, Doi, C & Lundholm, K (2000) Effect of cyclooxygenase and nitric oxide synthase inhibitors on tumor growth in mouse tumor models with and without cancer cachexia related to prostanoids. Cancer Research 60, 1742–1749.Google ScholarPubMed
Calder, PC (2003) Long-chain n-3 fatty acids and inflammation: potential application in surgical and trauma patients. Brazilian Journal of Medical and Biological Research 36, 433–446.CrossRefGoogle ScholarPubMed
Cariuk, P, Lorite, MJ, Todorov, PT, Field, WN, Wigmore, SJ & Tisdale, MJ (1997) Induction of cachexia in mice by a product isolated from the urine of cachectic cancer patients. British Journal of Cancer 76, 606–613.CrossRefGoogle ScholarPubMed
Cha, MC, Meckling, KA & Stewart, C (2002) Dietary docosahexaenoic acid levels influence the outcome of arabinosylcytosine chemotherapy in L1210 leukemic mice. Nutrition and Cancer 44, 176–181.CrossRefGoogle ScholarPubMed
Cha, SH, Fukushima, A, Sakuma, K & Kagawa, Y (2001) Chronic docosahexaenoic acid intake enhances expression of the gene for uncoupling protein 3 and affects pleiotropic mRNA levels in skeletal muscle of aged C57BL/6NJcl mice. Journal of Nutrition 131, 2636–2642.CrossRefGoogle ScholarPubMed
Chajes, V & Bougnoux, P (2003) Omega-6/omega-3 polyunsaturated fatty acid ratio and cancer. World Reviews of Nutrition and Dietetics 92, 133–151.Google ScholarPubMed
Chen, ZY & Istfan, NW (2000) Docosahexaenoic acid is a potent inducer of apoptosis in HT-29 colon cancer cells. Prostaglandins Leukotrienes and Essential Fatty Acids 63, 301–308.CrossRefGoogle ScholarPubMed
Chen, ZY & Istfan, NW (2001) Docosahexaenoic acid, a major constituent of fish oil diets, prevents activation of cyclin dependent kinases and S-phase entry by serum stimulation in HT-29 cells. Prostaglandins Leukotrienes and Essential Fatty Acids 64, 67–73.CrossRefGoogle Scholar
Chung, BH, Mitchell, SH, Zhang, JS & Young, CY (2001) Effects of docosahexaenoic acid and eicosapentaenoic acid on androgen-mediated cell growth and gene expression in LNCaP prostate cancer cells. Carcinogenesis 22, 1201–1206.CrossRefGoogle ScholarPubMed
Clarke, RG, Lund, EK, Latham, P, Pinder, AC & Johnson, IT (1999) Effect of eicosapentaenoic acid on the proliferation and incidence of apoptosis in the colorectal cell line HT29. Lipids 34, 1287–1295.CrossRefGoogle ScholarPubMed
Clemens, MR, Waladkhani, AR, Bublitz, K, Ehninger, G & Gey, KF (1997) Supplementation with antioxidants prior to bone marrow transplantation. Wiener Klinische Wochenschrift 109, 771–776.Google ScholarPubMed
Cognault, S, Jourdan, ML, Germain, E, Pitavy, R, Morel, E, Durand, G, Bougnoux, P & Lhuillery, C (2000) Effect of an alpha-linolenic acid-rich diet on rat mammary tumor growth depends on the dietary oxidative status. Nutrition and Cancer 36, 33–41.CrossRefGoogle ScholarPubMed
Cohen, LA (2000) Re: Meta-analysis: dietary fat intake, serum estrogen levels, and the risk of breast cancer. Journal of the National Cancer Institute 92, 78.CrossRefGoogle ScholarPubMed
Collett, ED, Davidson, LA, Fan, YY, Lupton, JR & Chapkin, RS (2001) n-6 and n-3 Polyunsaturated fatty acids differentially modulate oncogenic Ras activation in colonocytes. American Journal of Physiology 280, C1066–C1075.CrossRefGoogle ScholarPubMed
Conklin, KA (2002) Dietary polyunsaturated fatty acids: impact on cancer chemotherapy and radiation. Alternative Medicine Reviews 7, 4–21.Google ScholarPubMed
Connolly, JM, Gilhooly, EM & Rose, DP (1999) Effects of reduced dietary linoleic acid intake, alone or combined with an algal source of docosahexaenoic acid, on MDA-MB-231 breast cancer cell growth and apoptosis in nude mice. Nutrition and Cancer 35, 44–49.CrossRefGoogle ScholarPubMed
Cowan, KH, Batist, G, Tulpule, A, Sinha, BK & Myers, CE (1986) Similar biochemical changes associated with multidrug resistance in human breast cancer cells and carcinogen-induced resistance to xenobiotics in rats. Proceedings of the National Academy of Sciences USA 83, 9328–9332.CrossRefGoogle ScholarPubMed
Das, UN, Madhavi, N, Sravan, KG, Padma, M & Sangeetha, P (1998) Can tumour cell drug resistance be reversed by essential fatty acids and their metabolites? Prostaglandins Leukotrienes and Essential Fatty Acids 58, 39–54.CrossRefGoogle ScholarPubMed
Das, UN, Ramos, EG & Meguid, MM (2003) Metabolic alterations during inflammation and its modulation by central actions of omega-3 fatty acids. Current Opinion in Clinical Nutrition and Metabolic Care 6, 413–419.CrossRefGoogle ScholarPubMed
Davidson, LA, Lupton, JR, Jiang, YH & Chapkin, RS (1999) Carcinogen and dietary lipid regulate ras expression and localization in rat colon without affecting farnesylation kinetics. Carcinogenesis 20, 785–791.CrossRefGoogle ScholarPubMed
Davies, CL, Loizidou, M, Cooper, AJ & Taylor, I (1999) Effect of gamma-linolenic acid on cellular uptake of structurally related anthracyclines in human drug sensitive and multidrug resistant bladder and breast cancer cell lines. European Journal of Cancer 35, 1534–1540.CrossRefGoogle ScholarPubMed
de Deckere, EA (1999) Possible beneficial effect of fish and fish n-3 polyunsaturated fatty acids in breast and colorectal cancer. European Journal of Cancer Prevention 8, 213–221.CrossRefGoogle ScholarPubMed
Dennis, LK, Snetselaar, LG, Nothwehr, FK & Stewart, RE (2003) Developing a scoring method for evaluating dietary methodology in reviews of epidemiologic studies. Journal of the American Dietetic Association 103, 483–487.Google ScholarPubMed
Fan, YY, McMurray, DN, Ly, LH & Chapkin, RS (2003) Dietary (n-3) polyunsaturated fatty acids remodel mouse T-cell lipid rafts. Journal of Nutrition 133, 1913–1920.CrossRefGoogle ScholarPubMed
Fearon, KC, von Meyenfeldt, MF, Moses, AG, Van Geenen, R, Roy, A, Gouma, DJ, Giacosa, A, van Gossum, A, Bauer, J, Barber, MD, Aaronson, NK, Voss, AC & Tisdale, MJ (2003) Effect of a protein and energy dense n-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut 52, 1479–1486.CrossRefGoogle ScholarPubMed
Furukawa, K, Yamamori, H, Takagi, K, Hayashi, N, Suzuki, R, Nakajima, N & Tashiro, T (2002) Influences of soybean oil emulsion on stress response and cell-mediated immune function in moderately or severely stressed patients. Nutrition 18, 235–240.CrossRefGoogle ScholarPubMed
Germain, E, Chajes, V, Cognault, S, Lhuillery, C & Bougnoux, P (1998) Enhancement of doxorubicin cytotoxicity by polyunsaturated fatty acids in the human breast tumor cell line MDA-MB-231: relationship to lipid peroxidation. International Journal of Cancer 75, 578–583.3.0.CO;2-5>CrossRefGoogle ScholarPubMed
Germain, E, Lavandier, F, Chajes, V, Schubnel, V, Bonnet, P, Lhuillery, C & Bougnoux, P (1999) Dietary n-3 polyunsaturated fatty acids and oxidants increase rat mammary tumor sensitivity to epirubicin without change in cardiac toxicity. Lipids 34, Suppl., S203.CrossRefGoogle ScholarPubMed
Gogos, CA, Ginopoulos, P, Salsa, B, Apostolidou, E, Zoumbos, NC & Kalfarentzos, F (1998) Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy. Cancer 82, 395–402.3.0.CO;2-1>CrossRefGoogle ScholarPubMed
Goldstein, LJ, Pastan, I & Gottesman, MM (1992) Multidrug resistance in human cancer. Critical Reviews in Oncology and Hematology 12, 243–253.CrossRefGoogle ScholarPubMed
Gottesman, MM & Pastan, I (1993) Biochemistry of multidrug resistance mediated by the multidrug transporter. Annual Reviews of Biochemistry 62, 385–427.CrossRefGoogle ScholarPubMed
Griffini, P, Fehres, O, Klieverik, L, Vogels, IM, Tigchelaar, W, Smorenburg, SM & Van Noorden, CJ (1998) Dietary omega-3 polyunsaturated fatty acids promote colon carcinoma metastasis in rat liver. Cancer Research 58, 3312–3319.Google ScholarPubMed
Hardman, WE (2002) Omega-3 fatty acids to augment cancer therapy. Journal of Nutrition 132, 3508S–3512S.CrossRefGoogle ScholarPubMed
Hardman, WE, Avula, CP, Fernandes, G & Cameron, IL (2001) Three percent dietary fish oil concentrate increased efficacy of doxorubicin against MDA-MB 231 breast cancer xenografts. Clinical Cancer Research 7, 2041–2049.Google ScholarPubMed
Hardman, WE, Moyer, MP & Cameron, IL (1999) Fish oil supplementation enhanced CPT-11 (irinotecan) efficacy against MCF7 breast carcinoma xenografts and ameliorated intestinal side-effects. British Journal of Cancer 81, 440–448.CrossRefGoogle ScholarPubMed
Hardman, WE, Moyer, MP & Cameron, IL (2000) Dietary fish oil sensitizes A549 lung xenografts to doxorubicin chemotherapy. Cancer Letters 151, 145–151.CrossRefGoogle ScholarPubMed
Hardman, WE, Munoz, J Jr & Cameron, IL (2002) Role of lipid peroxidation and antioxidant enzymes in omega 3 fatty acids induced suppression of breast cancer xenograft growth in mice. Cancer Cell International 2, 10.CrossRefGoogle ScholarPubMed
Hong, MY, Chapkin, RS, Barhoumi, R, Burghardt, RC, Turner, ND, Henderson, CE, Sanders, LM, Fan, YY, Davidson, LA, Murphy, ME, Spinka, CM, Carroll, RJ & Lupton, JR (2002) Fish oil increases mitochondrial phospholipid unsaturation, upregulating reactive oxygen species and apoptosis in rat colonocytes. Carcinogenesis 23, 1919–1925.CrossRefGoogle ScholarPubMed
Hong, MY, Chapkin, RS, Davidson, LA, Turner, ND, Morris, JS, Carroll, RJ & Lupton, JR (2003) Fish oil enhances targeted apoptosis during colon tumor initiation in part by downregulating Bcl-2. Nutrition and Cancer 46, 44–51.CrossRefGoogle ScholarPubMed
Hrelia, S, Bordoni, A, Angeloni, C, Leoncini, E, Galina Toschi, T & Lercker, G & Biagi, PL (2002) Green tea extracts can counteract the modification of fatty acid composition induced by doxorubicin in cultured cardiomyocytes. Prostaglandins Leukotrienes and Essential Fatty Acids 66, 519–524.CrossRefGoogle ScholarPubMed
Hughes-Fulford, M, Chen, Y & Tjandrawinata, RR (2001) Fatty acid regulates gene expression and growth of human prostate cancer PC-3 cells. Carcinogenesis 22, 701–707.CrossRefGoogle ScholarPubMed
Islam-Ali, B, Khan, S, Price, SA & Tisdale, MJ (2001) Modulation of adipocyte G-protein expression in cancer cachexia by a lipid-mobilizing factor (LMF). British Journal of Cancer 85, 758–763.CrossRefGoogle ScholarPubMed
Iwamoto, S, Senzaki, H, Kiyozuka, Y, Ogura, E, Takada, H, Hioki, K & Tsubura, A (1998) Effects of fatty acids on liver metastasis of ACL-15 rat colon cancer cells. Nutrition and Cancer 31, 143–150.CrossRefGoogle ScholarPubMed
Jatoi, A, Rowland, M, Loprinzi, CL, Sloan, JA, Dakhil, SR, MacDonald, N, Gagnon, B, Novotny, PJ, Malliard, JA & Krook, JE (2003) An eicosapentaenoic acid (EPA)-enriched supplement versus megestrol acetate (MA) versus both for patients with cancer-associated wasting. A collaborative effort from the North Central Cancer Treatment Group (NCCTG) and the National Cancer Institute of Canada (NCIC). American Society of Clinical Oncology 22, 743.Google Scholar
Jho, DH, Babcock, TA, Tevar, R, Helton, WS & Espat, NJ (2002) Eicosapentaenoic acid supplementation reduces tumor volume and attenuates cachexia in a rat model of progressive non-metastasizing malignancy. Journal of Parenteral and Enteral Nutrition 26, 291–297.CrossRefGoogle Scholar
Jiang, WG, Bryce, RP & Horrobin, DF (1998) Essential fatty acids: molecular and cellular basis of their anti-cancer action and clinical implications. Critical Reviews Oncology/Hematology 27, 179–209.CrossRefGoogle ScholarPubMed
Klein, V, Chajes, V, Germain, E, Schulgen, G, Pinault, M, Malvy, D, Lefrancq, T, Fignon, A, Le Floch, O, Lhuillery, C & Bougnoux, P (2000) Low alpha-linolenic acid content of adipose breast tissue is associated with an increased risk of breast cancer. European Journal of Cancer 36, 335–340.CrossRefGoogle ScholarPubMed
Kotler, DP (2000) Cachexia. Annals of Internal Medicine 133, 622–634.CrossRefGoogle ScholarPubMed
Kris-Etherton, PM, Harris, WS & Appel, LJ (2002) Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 106, 2747–2757.CrossRefGoogle ScholarPubMed
Kumar, GS & Das, UN (1995) Free radical-dependent suppression of growth of mouse myeloma cells by alpha-linolenic and eicosapentaenoic acids in vitro. Cancer Letters 92, 27–38.CrossRefGoogle ScholarPubMed
Laviano, A, Meguid, MM & Rossi-Fanelli, F (2003) Cancer anorexia: clinical implications, pathogenesis, and therapeutic strategies. Lancet Oncology 4, 686–694.CrossRefGoogle ScholarPubMed
Lavie, Y, Fiucci, G, Czarny, M & Liscovitch, M (1999) Changes in membrane micordomains and caveolae constituents in multidrug-resistant cancer cells. Lipids 34, Suppl., S57–S63.CrossRefGoogle Scholar
Lavie, Y & Liscovitch, M (2000) Changes in lipid and protein constituents of rafts and caveolae in multidrug resistant cancer cells and their functional consequences. Glycoconjugate Journal 17, 253–259.CrossRefGoogle ScholarPubMed
Liu, G, Bibus, DM, Bode, AM, Ma, WY, Holman, RT & Dong, Z (2001) Omega 3 but not omega 6 fatty acids inhibit AP-1 activity and cell transformation in JB6 cells. Proceedings of the National Academy of Sciences USA 98, 7510–7515.CrossRefGoogle Scholar
Liu, P, Rudick, M & Anderson, RGW (2002) Multiple functions of caveolin-1. Journal of Biological Chemistry 277, 41295–41298.CrossRefGoogle ScholarPubMed
Liu, QY & Tan, BK (2000) Effects of cis-unsaturated fatty acids on doxorubicin sensitivity in P388/DOX resistant and P388 parental cell lines. Life Sciences 67, 1207–1218.CrossRefGoogle ScholarPubMed
Lorite, MJ, Smith, HJ, Arnold, JA, Morris, A, Thompson, MG & Tisdale, MJ (2001) Activation of ATP-ubiquitin-dependent proteolysis in skeletal muscle in vivo and murine myoblasts in vitro by a proteolysis-inducing factor (PIF). British Journal of Cancer 85, 297–302.CrossRefGoogle ScholarPubMed
Lorite, MJ, Thompson, MG, Drake, JL, Carling, G & Tisdale, MJ (1998) Mechanism of muscle protein degradation induced by a cancer cachectic factor. British Journal of Cancer 78, 850–856.CrossRefGoogle ScholarPubMed
MacDonald, N, Easson, AM, Mazurak, VC, Dunn, GP & Baracos, VE (2003) Understanding and managing cancer cachexia. Journal of the American College of Surgeons 197, 143–161.CrossRefGoogle ScholarPubMed
McEntee, MF & Whelan, J (2002) Dietary polyunsaturated fatty acids and colorectal neoplasia. Biomedical Pharmacotherapy 56, 380–387.CrossRefGoogle ScholarPubMed
Mariadason, JM, Arango, D, Corner, GA, Aranes, MJ, Hotchkiss, KA, Yang, W & Augenlicht, LH (2002) A gene expression profile that defines colon cell maturation in vitro. Cancer Research 62, 4804.Google ScholarPubMed
Marra, CA, de Alaniz, MJ & Brenner, RR (1986) Modulation of delta 6 and delta 5 rat liver microsomal desaturase activities by dexamethasone-induced factor. Biochimica et Biophysica Acta 879, 388–393.CrossRefGoogle ScholarPubMed
Meguid, MM, Fetissov, SO, Varma, M, Sato, T, Zhang, L, Laviano, A & Rossi-Fanelli, F (2000) Hypothalamic dopamine and serotonin in the regulation of food intake. Nutrition 16, 843–857.CrossRefGoogle ScholarPubMed
Menendez, JA, del Mar, B, Montero, S, Sevilla, E, Escrich, E, Solanas, M, Cortes-Funes, H & Colomer, R (2001) Effects of gamma-linolenic acid and oleic acid on paclitaxel cytotoxicity in human breast cancer cells. European Journal of Cancer 37, 402–413.CrossRefGoogle ScholarPubMed
Mirnikjoo, B, Brown, SE, Chang, WC, Morris, JS, Wang, N, Carroll, RJ, Turner, ND, Lupton, JR & Chapkin, RS (2001) Protein kinase inhibition by omega-3 fatty acids. Journal of Biological Chemistry 276, 10888–10896.CrossRefGoogle ScholarPubMed
Nair, SS, Leitch, J & Garg, ML (2001) n-3 Polyunsaturated fatty acid supplementation alters inositol phosphate metabolism and protein kinase C activity in adult porcine cardiac myocytes. Journal of Nutritional Biochemistry 12, 7–13.CrossRefGoogle ScholarPubMed
Nakamura, S & Nishizuka, Y (1994) Lipid mediators and protein kinase C activation for the intracellular signaling network. Journal of Biochemistry 115, 1029–1034.CrossRefGoogle ScholarPubMed
Narayanan, BA, Narayanan, NK & Reddy, BS (2001) Docosahexaenoic acid regulated genes and transcription factors inducing apoptosis in human colon cancer cells. International Journal of Oncology 19, 1255–1262.Google ScholarPubMed
Narayanan, BA, Narayanan, NK, Simi, B & Reddy, BS (2003) Modulation of inducible nitric oxide synthase and related proinflammatory genes by the omega-3 fatty acid docosahexaenoic acid in human colon cancer cells. Cancer Research 63, 972–979.Google ScholarPubMed
Ogilvie, GK, Fettman, MJ, Mallinckrodt, CH, Walton, JA, Hansen, RA, Davenport, DJ, Gross, KL, Richardson, KL, Rogers, Q & Hand, MS (2000) Effect of fish oil, arginine, and doxorubicin chemotherapy on remission and survival time for dogs with lymphoma: a double-blind, randomized placebo-controlled study. Cancer 88, 1916–1928.3.0.CO;2-F>CrossRefGoogle ScholarPubMed
Palakurthi, SS, Fluckiger, R, Aktas, H, Changolkar, AK, Shahsafaei, A, Harneit, S, Kilic, E & Halperin, JA (2000) Inhibition of translation initiation mediates the anticancer effect of the n-3 polyunsaturated fatty acid eicosapentaenoic acid. Cancer Research 60, 2919–2925.Google ScholarPubMed
Pandian, SS, Sneddon, AA, Bestwick, CS, McClinton, S, Grant, I, Wahle, KW & Heys, SD (2001) Fatty acid regulation of protein kinase C isoforms in prostate cancer cells. Biochemical and Biophysical Research Communications 283, 806–812.CrossRefGoogle ScholarPubMed
Pasqualini, ME, Heyd, VL, Manzo, P & Eynard, AR (2003) Association between E-cadherin expression by human colon, bladder and breast cancer cells and the 13-HODE:15-HETE ratio. A possible role of their metastatic potential. Prostaglandins Leukotrienes and Essential Fatty Acids 68, 9–16.CrossRefGoogle ScholarPubMed
Pike, LJ (2003) Lipid rafts: bringing order to chaos. Journal of Lipid Research 44, 655–667.CrossRefGoogle ScholarPubMed
Pike, LJ, Han, X, Chung, K-N & Gross, RW (2002) Lipid rafts are enriched in arachidonic acid and plasmenylethanolamine and their composition is independent of caveolin-1 expression: a quantitative electrospray ionization/mass spectrometric analysis. Biochemistry 41, 2075–2088.CrossRefGoogle ScholarPubMed
Pratt, VC, Watanabe, S, Bruera, E, Mackey, J, Clandinin, MT, Baracos, VE & Field, CJ (2002) Plasma and neutrophil fatty acid composition in advanced cancer patients and response to fish oil supplementation. British Journal of Cancer 87, 1370–1378.CrossRefGoogle ScholarPubMed
Ravagnan, L, Roumier, T & Kroemer, G (2002) Mitochondria, the killer organelles and their weapons. Journal of Cellular Physiology 192, 131–137.CrossRefGoogle ScholarPubMed
Rhodes, DR, Barrette, TR, Rubin, MA, Ghosh, D & Chinnaiyan, AM (2002) Meta-analysis of microarrays: interstudy validation of gene expression profiles reveals pathway dysregulation in prostate cancer. Cancer Research 62, 4427–4433.Google ScholarPubMed
Robinson, LE, Clandinin, MT & Field, CJ (2001) R3230AC rat mammary tumor and dietary long-chain (n-3) fatty acids change immune cell composition and function during mitogen activation. Journal of Nutrition 131, 2021–2027.CrossRefGoogle ScholarPubMed
Rose, DP & Connolly, JM (1993) Effects of dietary omega-3 fatty acids on human breast cancer growth and metastases in nude mice. Journal of the National Cancer Institute 85, 1743–1747.CrossRefGoogle ScholarPubMed
Rose, DP & Connolly, JM (1999 a) Antiangiogenicity of docosahexaenoic acid and its role in the suppression of breast cancer cell growth in nude mice. International Journal of Oncology 15, 1011–1015.Google ScholarPubMed
Rose, DP & Connolly, JM (1999 b) Omega-3 fatty acids as cancer chemopreventive agents. Pharmacology and Therapeutics 83, 217–244.CrossRefGoogle ScholarPubMed
Rose, DP & Connolly, JM (2000) Regulation of tumor angiogenesis by dietary fatty acids and eicosanoids. Nutrition and Cancer 37, 119–127.CrossRefGoogle ScholarPubMed
Ross, JA & Fearon, KC (2002) Eicosanoid-dependent cancer cachexia and wasting. Current Opinion in Clinical Nutrition and Metabolic Care 5, 241–248.CrossRefGoogle ScholarPubMed
Rudra, PK & Krokan, HE (2001) Cell-specific enhancement of doxorubicin toxicity in human tumour cells by docosahexaenoic acid. Anticancer Research 21, 29–38.Google ScholarPubMed
Sasaki, T, Kobayashi, Y, Shimizu, J, Wada, M, In'nami, S, Kanke, Y & Takita, T (1998) Effects of dietary n-3-to-n-6 polyunsaturated fatty acid ratio on mammary carcinogenesis in rats. Nutrition and Cancer 30, 137–143.CrossRefGoogle ScholarPubMed
Sauer, LA, Dauchy, RT & Blask, DE (2000) Mechanism for the antitumor and anticachectic effects of n-3 fatty acids. Cancer Research 60, 5289–5295.Google ScholarPubMed
Senchenkov, A, Litvak, DA & Cabot, MC (2001) Targeting ceramide metabolism – a strategy for overcoming drug resistance. Journal of the National Cancer Institute 93, 347–357.CrossRefGoogle ScholarPubMed
Senzaki, H, Iwamoto, S, Ogura, E, Kiyozuka, Y, Arita, S, Kurebayashi, J, Takada, H, Hioki, K & Tsubura, A (1998) Dietary effects of fatty acids on growth and metastasis of KPL-1 human breast cancer cells in vivo and in vitro. Anticancer Research 18, 1621–1627.Google ScholarPubMed
Shappell, SB, Olson, SJ, Hannah, SE, Manning, S, Roberts, RL, Masumori, N, Jisaka, M, Boeglin, WE, Vader, V, Dave, DS, Shook, MF, Thomas, TZ, Funk, CD, Brash, AR & Matusik, RJ (2003) Elevated expression of 12/15-lipoxygenase and cyclooxygenase-2 in a transgenic mouse model of prostate carcinoma. Cancer Research 63, 2256–2267.Google Scholar
Siddiqui, RA, Jenski, LJ, Neff, K, Harvey, K, Kovacs, RJ & Stillwell, W (2001) Docosahexaenoic acid induces apoptosis in Jurkat cells by a protein phosphatase-mediated process. Biochimica et Biophysica Acta 1499, 265–275.CrossRefGoogle ScholarPubMed
Sidorenko, I, Frantsiiants, EM, Tkacheva, EM, Musienko, NV & Kartashov, SZ (1998) The effect of chemotherapeutic drugs on free-radical oxidation of lipids in the lymph of lung cancer patients (in Russian). Voprosy Onkologii 44, 297–299.Google Scholar
Siegfried, JM, Burke, TG & Tritton, TR (1985) Cellular transport of anthracyclines by passive diffusion. Implications for drug resistance. Biochemistry and Pharmacology 34, 593–598.CrossRefGoogle ScholarPubMed
Sikic, BI (1997) Pharmacologic approaches to reversing multidrug resistance. Seminars in Hematology 34, 40–47.Google ScholarPubMed
Simonsen, N, van't Veer, P, Strain, JJ, Martin-Moreno, JM, Huttunen, JK, Navajas, JF, Martin, BC, Thamm, M, Kardinaal, AF, Kok, FJ & Kohlmeier, L (1998) Adipose tissue omega-3 and omega-6 fatty acid content and breast cancer in the EURAMIC study. European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Breast Cancer. American Journal of Epidemiology 147, 342–352.CrossRefGoogle ScholarPubMed
Simopoulos, AP (1999) Evolutionary aspects of omega-3 fatty acids in the food supply. Prostaglandins Leukotrienes and Essential Fatty Acids 60, 421–429.CrossRefGoogle ScholarPubMed
Simopoulos, AP (2002) Omega-3 fatty acids in inflammation and autoimmune diseases. Journal of the American College of Nutrition 21, 495–505.CrossRefGoogle ScholarPubMed
Smith, HJ, Lorite, MJ & Tisdale, MJ (1999) Effect of a cancer cachectic factor on protein synthesisk/degradation in murine C2C12 myoblasts: modulation by eicosapentaenoic acid. Cancer Research 59, 5507–5513.Google ScholarPubMed
Smith, HJ & Tisdale, MJ (2003) Induction of apoptosis by a cachectic-factor in murine myotubes and inhibition by eicosapentaenoic acid. Apoptosis 8, 161–169.CrossRefGoogle ScholarPubMed
Spector, AA & Burns, CP (1987) Biological and therapeutic potential of membrane lipid modification in tumors. Cancer Research 47, 4529–4537.Google ScholarPubMed
Stoll, BA (2001) n-3 Fatty acids and lipid peroxidation in breast cancer inhibition. British Journal of Nutrition 87, 193–198.CrossRefGoogle Scholar
Stulnig, TM, Berger, M, Sigmund, T, Raederstorff, D, Stockinger, H & Waldhausl, W (1998) Polyunsaturated fatty acids inhibit T cell signal transduction by modification of detergent-insoluble membrane domains. Journal of Cell Biology 143, 637–644.CrossRefGoogle ScholarPubMed
Stulnig, TM, Huber, J, Leitinger, N, Imre, E-M, Angelisova, P, Nowotny, P & Waldhausl, W (2001) Polyunsaturated eicosapentaenoic acid displaces proteins from membrane rafts by altering raft lipid composition. Journal of Biological Chemistry 276, 37335–37340.CrossRefGoogle ScholarPubMed
Swinnen, JV, Van Veldhoven, PP, Timmermans, L, De Schrijver, E, Brusselmans, K, Vanderhoydonc, F, Van de Sande, T, Heemers, H, Heyns, W & Verhoeven, G (2003) Fatty acid synthase drives the synthesis of phospholipids partitioning into detergent-resistant membrane microdomains. Biochemical and Biophysical Research Communications 21, 898–903.CrossRefGoogle Scholar
Takahata, K, Tada, M, Yazawa, K & Tamaki, T (1999) Protection from chemotherapy-induced alopecia by docosahexaenoic acid. Lipids 34, Suppl., S105.CrossRefGoogle ScholarPubMed
Temple, NJ (2002) Nutrition and disease: challenges of research design. Nutrition 18, 343–347.CrossRefGoogle ScholarPubMed
Terry, PD, Rohan, TE & Wolk, A (2003) Intakes of fish and marine fatty acids and the risks of cancers of the breast and prostate and of other hormone-related cancers: a review of the epidemiologic evidence. American Journal of Clinical Nutrition 77, 532–543.CrossRefGoogle ScholarPubMed
Theile, A & Kemper, P (1998) Bleomycin-induced pulmonary fibrosis following chemotherapy of ovarian granulosa cell tumor (in German). Pneumologie 52, 325–332.Google Scholar
Thoennes, SR, Tate, PL, Price, TM & Kilgore, MW (2000) Differential transcriptional activation of peroxisome proliferator-activated receptor gamma by omega-3 and omega-6 fatty acids in MCF-7 cells. Molecular and Cellular Endocrinology 160, 67–73.CrossRefGoogle ScholarPubMed
Tisdale, MJ (2001) Loss of skeletal muscle in cancer: biochemical mechanisms. Frontiers in Bioscience 6, D164–D174.Google ScholarPubMed
Tisdale, MJ (2003) The ‘cancer cachectic factor’. Supportive Care in Cancer 11, 73–78.CrossRefGoogle ScholarPubMed
Todorov, PT, Field, WN & Tisdale, MJ (1999) Role of a proteolysis-inducing factor (PIF) in cachexia induced by a human melanoma (G361). British Journal of Cancer 80, 1734–1737.CrossRefGoogle ScholarPubMed
Tsuji, M, Murota, S & Morita, I (2003) Docosapentaenoic acid (22:5, n-3) suppressed tube-forming activity in endothelial cells induced by vascular endothelial growth factor. Prostaglandins Leukotrienes and Essential Fatty Acids 68, 337–342.CrossRefGoogle Scholar
Verstovsek, G, Byrd, A, Frey, MR, Petrelli, NJ & Black, JD (1998) Colonocyte differentiation is associated with increased expression and altered distribution of protein kinase C isozymes. Gastroenterology 115, 75–85.CrossRefGoogle ScholarPubMed
Wahle, KWJ & Heys, SD (2002) Cell signal mechanisms, conjugated linoleic acids (CLAs) and anti-tumorigenesis. Prostaglandins Leukotrienes and Essential Fatty Acids 67, 183–186.CrossRefGoogle ScholarPubMed
Wang, H, Storlien, LH & Huang, XF (2002) Effects of dietary fat types on body fatness, leptin, and ARC leptin receptor, NPY, and AgRP mRNA expression. American Journal of Physiology 282, E1352–E1359.Google ScholarPubMed
Weisburger, JH (2000) Prevention of cancer and other chronic diseases worldwide based on sound mechanisms. Biofactors 12, 73–81.CrossRefGoogle ScholarPubMed
Whelan, J, Petrik, MB, McEntee, MF & Obukowicz, MG (2002) Dietary EPA reduces tumor load in ApcMin/+ mice by altering arachidonic acid metabolism, but conjugated linoleic acid, gamma- and alpha-linolenic acids have no effect. Advances in Experimental Medicine and Biology 507, 579–584.CrossRefGoogle ScholarPubMed
Whitehouse, AS, Smith, HJ, Drake, JL & Tisdale, MJ (2001) Mechanism of attenuation of skeletal muscle protein catabolism in cancer cachexia by eicosapentaenoic acid. Cancer Research 61, 3604–3609.Google ScholarPubMed
Whitehouse, AS & Tisdale, MJ (2001) Downregulation of ubiquitin-dependent proteolysis by eicosapentaenoic acid in acute starvation. Biochemical and Biophysical Research Communications 285, 598–602.CrossRefGoogle ScholarPubMed
Wigmore, SJ, Barber, MD, Ross, JA, Tisdale, MJ & Fearon, KC (2000) Effect of oral eicosapentaenoic acid on weight loss in patients with pancreatic cancer. Nutrition and Cancer 36, 177–184.CrossRefGoogle ScholarPubMed
Wigmore, SJ, McMahon, AJ, Sturgeon, CM & Fearon, KC (2001) Acute-phase protein response, survival and tumour recurrence in patients with colorectal cancer. British Journal of Surgery 88, 255–260.CrossRefGoogle ScholarPubMed
Woods, JM, Mogollon, A, Amin, MA, Martinez, RJ & Koch, AE (2003) The role of COX-2 in angiogenesis and rheumatoid arthritis. Experimental and Molecular Pathology 74, 282–290.CrossRefGoogle ScholarPubMed
Woutersen, RA, Appel, MJ, Garderen-Hoetmer, A & Wijnands, MV (1999) Dietary fat and carcinogenesis. Mutation Research 443, 111–127.CrossRefGoogle ScholarPubMed
Yam, D, Peled, A & Shinitzky, M (2001) Suppression of tumor growth and metastasis by dietary fish oil combined with vitamins E and C and cisplatin. Cancer Chemotherapy and Pharmacology 47, 34–40.CrossRefGoogle Scholar
Yamamoto, D, Kiyozuka, Y, Adachi, Y, Takada, H, Hioki, K & Tsubura, A (1999) Synergistic action of apoptosis induced by eicosapentaenoic acid and TNP-470 on human breast cancer cells. Breast Cancer Research and Treatment 55, 149–160.CrossRefGoogle ScholarPubMed
Yamauchi, T, Watanabe, M, Hasegawa, H, Nishibori, H, Ishii, Y, Tatematsu, H, Yamamoto, K, Kubota, T & Kitajima, M (2003) The potential for a selective cyclooxygenase-2 inhibitor in the prevention of liver metastasis in human colorectal cancer. Anticancer Research 23, 245–249.Google ScholarPubMed
Zock, PL (2001) Dietary fats and cancer. Current Opinion in Lipidology 12, 5–10.CrossRefGoogle ScholarPubMed
Zuijdgeest-van Leeuwen, SD, van der Heijden, MS, Rietveld, T, van den Berg, JWO, Tilanus, HW, Burgers, JA, Paul Wilson, JH & Dagnelie, PC (2002) Fatty acid composition of plasma lipids in patients with pancreatic, lung and oesophageal cancer in comparison with healthy subjects. Clinical Nutrition 21, 225–230.CrossRefGoogle ScholarPubMed
Zweifel, BS, Davis, TW, Ornberg, RL & Masferrer, JL (2002) Direct evidence for a role of cyclooxygenase 2-derived prostaglandin E2 in human head and neck xenograft tumors. Cancer Research 62, 6706–6711.Google ScholarPubMed