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Stearidonic acid-enriched flax oil reduces the growth of human breast cancer in vitro and in vivo


The 20 and 22 carbon n-3 long-chain polyunsaturated fatty acids (LCPUFA) inhibit the growth of tumors in vitro and in animal models, but less is known about the 18 carbon n-3, stearidonic acid (SDA). This study aimed to establish and determine a mechanism for the anti-cancer activity of SDA-enriched oil (SO). SO (26 % of lipid) was produced by genetically engineering flax and used to treat human tumorigenic (MDA-MB-231, MCF-7) and non-tumorigenic (MCF-12A) breast cells. Nu/nu mice bearing MDA-MB-231 tumor were fed SO (SDA, 4 % of fat). Cell/tumor growth, phospholipid (PL) composition, apoptosis, CD95, and pro-apoptotic molecules were determined in SO-treated cells/tumors. Compared to a control lipid mixture, SO reduced (p < 0.05) the number of tumorigenic, but not MCF-12A cells, and resulted in higher concentration of most of the n-3 fatty acids in PL of all cells (p < 0.05). However, docosapentaenoic acid increased only in tumorigenic cells (p < 0.05). SO diet decreased tumor growth and resulted in more n-3 LCPUFA, including DPA and less arachidonic acid (AA) levels in major tumor PL (p < 0.05). Treatment of MDA-MB-231 cells/tumors with SO resulted in more apoptotic cells (in tumors) and in vivo and in vitro, more CD95+ positive cells and a higher expression of apoptotic molecules caspase-10, Bad, or Bid (p < 0.05). Supplementing SO alters total PL and PL classes by increasing membrane content of n-3 LCPUFA and lowering AA (in vivo), which is associated with increased CD95-mediated apoptosis, thereby suggesting a possible mechanism for reduce tumor survival.

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Arachidonic acid


α-linolenic acid


Fas ligand death receptor


Dihomo γ-linolenic acid


Docosahexaenoic acid


Docosapentaenoic acid


Eicosapentaenoic acid


Eicosatetraenoic acid


Gas chromatography


γ-linolenic acid


Linoleic acid


Long-chain polyunsaturated fatty acid


Oleic acid












Stearidonic acid


SDA-enriched oil


  1. 1.

    Chajes V, Sattler W, Stranzl A, Kostner GM (1995) Influence of n-3 fatty acids on the growth of human breast cancer cells in vitro: relationship to peroxides and vitamin-E. Breast Cancer Res Treat 34(3):199–212

    CAS  PubMed  Article  Google Scholar 

  2. 2.

    Ewaschuk JB, Newell M, Field CJ (2012) Docosahexanoic acid improves chemotherapy efficacy by inducing CD95 translocation to lipid rafts in ER(-) breast cancer cells. Lipids 47(11):1019–1030. doi:10.1007/s11745-012-3717-7

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    Grammatikos SI, Subbaiah PV, Victor TA, Miller WM (1994) n-3 and n-6 fatty acid processing and growth effects in neoplastic and non-cancerous human mammary epithelial cell lines. Br J Cancer 70(2):219–227

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  4. 4.

    Schley PD, Jijon HB, Robinson LE, Field CJ (2005) Mechanisms of omega-3 fatty acid-induced growth inhibition in MDA-MB-231 human breast cancer cells. Breast Cancer Res Treat 92(2):187–195. doi:10.1007/s10549-005-2415-z

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Kang KS, Wang P, Yamabe N, Fukui M, Jay T, Zhu BT (2010) Docosahexaenoic acid induces apoptosis in MCF-7 cells in vitro and in vivo via reactive oxygen species formation and caspase 8 activation. PLoS ONE 5(4):e10296. doi:10.1371/journal.pone.0010296

    PubMed Central  PubMed  Article  Google Scholar 

  6. 6.

    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. J Nutr 131(7):2021–2027

    CAS  PubMed  Google Scholar 

  7. 7.

    Rose DP, Connolly JM (1999) Omega-3 fatty acids as cancer chemopreventive agents. Pharmacol Ther 83(3):217–244

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Rose DP, Connolly JM, Rayburn J, Coleman M (1995) Influence of diets containing eicosapentaenoic or docosahexaenoic acid on growth and metastasis of breast cancer cells in nude mice. J Natl Cancer Inst 87(8):587–592

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    Wu M, Harvey KA, Ruzmetov N, Welch ZR, Sech L, Jackson K, Stillwell W, Zaloga GP, Siddiqui RA (2005) Omega-3 polyunsaturated fatty acids attenuate breast cancer growth through activation of a neutral sphingomyelinase-mediated pathway. Int J Cancer 117(3):340–348. doi:10.1002/ijc.21238

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Field CJ, Schley PD (2004) Evidence for potential mechanisms for the effect of conjugated linoleic acid on tumor metabolism and immune function: lessons from n-3 fatty acids. Am J Clin Nutr 79(6 Suppl):1190S–1198S

    CAS  PubMed  Google Scholar 

  11. 11.

    Sawyer MB, Field CJ (2010) Possible Mechanism of n-3 PUFA anti-tumor action. In: Calviello G, Serini S (eds) Dietary omega-3 polyunsaturated fatty acids and cancer, Diet and Cancer, vol 1. Springer Science, New York, pp 3–38. doi:10.1007/978-90-481-3579-0_1

    Chapter  Google Scholar 

  12. 12.

    Gu Z, Suburu J, Chen H, Chen YQ (2013) Mechanisms of omega-3 polyunsaturated fatty acids in prostate cancer prevention. Biomed Res Int 2013:824563. doi:10.1155/2013/824563

    PubMed Central  PubMed  Google Scholar 

  13. 13.

    Hardman WE (2004) (n-3) Fatty acids and cancer therapy. J Nutr 134(12 Suppl):3427S–3430S

    CAS  PubMed  Google Scholar 

  14. 14.

    Deshpande R, Mansara P, Suryavanshi S, Kaul-Ghanekar R (2013) Alpha-linolenic acid regulates the growth of breast and cervical cancer cell lines through regulation of NO release and induction of lipid peroxidation. J Mol Biol 2:6–17

    CAS  Google Scholar 

  15. 15.

    Corsetto PA, Montorfano G, Zava S, Jovenitti IE, Cremona A, Berra B, Rizzo AM (2011) Effects of n-3 PUFAs on breast cancer cells through their incorporation in plasma membrane. Lipids Health Dis 10:73. doi:10.1186/1476-511X-10-73

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  16. 16.

    Baumgartner P, Geiger M, Zieseniss S, Malleier J, Huntington JA, Hochrainer K, Bielek E, Stoeckelhuber M, Lauber K, Scherfeld D, Schwille P, Waldele K, Beyer K, Engelmann B (2007) Phosphatidylethanolamine critically supports internalization of cell-penetrating protein C inhibitor. J Cell Biol 179(4):793–804. doi:10.1083/jcb.200707165

    PubMed Central  PubMed  Article  Google Scholar 

  17. 17.

    Neri LM, Bortul R, Borgatti P, Tabellini G, Baldini G, Capitani S, Martelli AM (2002) Proliferating or differentiating stimuli act on different lipid-dependent signaling pathways in nuclei of human leukemia cells. Mol Biol Cell 13(3):947–964. doi:10.1091/mbc.01-02-0086

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  18. 18.

    Wright MM, Howe AG, Zaremberg V (2004) Cell membranes and apoptosis: role of cardiolipin, phosphatidylcholine, and anticancer lipid analogues. Biochem Cell Biol 82(1):18–26. doi:10.1139/o03-092

    CAS  PubMed  Article  Google Scholar 

  19. 19.

    Yao Y, Huang C, Li ZF, Wang AY, Liu LY, Zhao XG, Luo Y, Ni L, Zhang WG, Song TS (2009) Exogenous phosphatidylethanolamine induces apoptosis of human hepatoma HepG2 cells via the bcl-2/Bax pathway. World J Gastroenterol WJG 15(14):1751–1758

    CAS  Article  Google Scholar 

  20. 20.

    Wang D, Dubois RN (2010) Eicosanoids and cancer. Nature reviews. Cancer 10(3):181–193. doi:10.1038/nrc2809

    CAS  PubMed Central  PubMed  Google Scholar 

  21. 21.

    Leitzmann MF, Stampfer MJ, Michaud DS, Augustsson K, Colditz GC, Willett WC, Giovannucci EL (2004) Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. Am J Clin Nutr 80(1):204–216

    CAS  PubMed  Google Scholar 

  22. 22.

    Petrik MB, McEntee MF, Johnson BT, Obukowicz MG, Whelan J (2000) Highly unsaturated (n-3) fatty acids, but not alpha-linolenic, conjugated linoleic or gamma-linolenic acids, reduce tumorigenesis in Apc(Min/+) mice. J Nutr 130(10):2434–2443

    CAS  PubMed  Google Scholar 

  23. 23.

    Burdge GC, Wootton SA (2002) Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. Br J Nutr 88(4):411–420. doi:10.1079/BJN2002689

    CAS  PubMed  Article  Google Scholar 

  24. 24.

    Emken EA, Adlof RO, Gulley RM (1994) Dietary linoleic acid influences desaturation and acylation of deuterium-labeled linoleic and linolenic acids in young adult males. Biochim Biophys Acta 1213(3):277–288

    CAS  PubMed  Article  Google Scholar 

  25. 25.

    Yamazaki K, Fujikawa M, Hamazaki T, Yano S, Shono T (1992) Comparison of the conversion rates of alpha-linolenic acid (18:3(n-3)) and stearidonic acid (18:4(n-3)) to longer polyunsaturated fatty acids in rats. Biochim Biophys Acta 1123(1):18–26

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Cantrill RC, Huang YS, Ells GW, Horrobin DF (1993) Comparison of the metabolism of alpha-linolenic acid and its delta 6 desaturation product, stearidonic acid, in cultured NIH-3T3 cells. Lipids 28(3):163–166

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Abbadi A, Domergue F, Bauer J, Napier JA, Welti R, Zahringer U, Cirpus P, Heinz E (2004) Biosynthesis of very-long-chain polyunsaturated fatty acids in transgenic oilseeds: constraints on their accumulation. Plant Cell 16(10):2734–2748. doi:10.1105/tpc.104.026070

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  28. 28.

    Ruiz-Lopez N, Haslam RP, Venegas-Caleron M, Larson TR, Graham IA, Napier JA, Sayanova O (2009) The synthesis and accumulation of stearidonic acid in transgenic plants: a novel source of ‘heart-healthy’ omega-3 fatty acids. Plant Biotechnol J 7(7):704–716. doi:10.1111/j.1467-7652.2009.00436.x

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Eckert H, La Vallee B, Schweiger BJ, Kinney AJ, Cahoon EB, Clemente T (2006) Co-expression of the borage Delta 6 desaturase and the Arabidopsis Delta 15 desaturase results in high accumulation of stearidonic acid in the seeds of transgenic soybean. Planta 224(5):1050–1057. doi:10.1007/s00425-006-0291-3

    CAS  PubMed  Article  Google Scholar 

  30. 30.

    Harris WS (2012) Stearidonic acid-enhanced soybean oil: a plant-based source of (n-3) fatty acids for foods. J Nutr 142(3):600S–604S. doi:10.3945/jn.111.146613

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    Chang NW, Wu CT, Chen DR, Yeh CY, Lin C (2013) High levels of arachidonic acid and peroxisome proliferator-activated receptor-alpha in breast cancer tissues are associated with promoting cancer cell proliferation. J Nutr Biochem 24(1):274–281. doi:10.1016/j.jnutbio.2012.06.005

    CAS  PubMed  Article  Google Scholar 

  32. 32.

    Maillard V, Hoinard C, Steghens JP, Jourdan ML, Pinault M, Bougnoux P, Chajes V (2002) Interaction of dietary beta-carotene and alpha-linolenic acid: effect on promotion of experimental mammary tumours. IARC Sci Publ 156:403–404

    CAS  PubMed  Google Scholar 

  33. 33.

    Reyes N, Reyes I, Tiwari R, Geliebter J (2004) Effect of linoleic acid on proliferation and gene expression in the breast cancer cell line T47D. Cancer Lett 209(1):25–35. doi:10.1016/j.canlet.2003.12.010

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Hong H, Datla N, Reed DW, Covello PS, MacKenzie SL, Qiu X (2002) High-level production of gamma-linolenic acid in Brassica juncea using a delta6 desaturase from Pythium irregulare. Plant Physiol 129(1):354–362. doi:10.1104/pp.001495

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  35. 35.

    Wu G, Truksa M, Datla N, Vrinten P, Bauer J, Zank T, Cirpus P, Heinz E, Qiu X (2005) Stepwise engineering to produce high yields of very long-chain polyunsaturated fatty acids in plants. Nat Biotechnol 23(8):1013–1017. doi:10.1038/nbt1107

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    Mlynarova L, Bauer M, Nap JP, Pretova A (1994) High efficiency Agrobacterium-mediated gene transfer to flax. Plant Cell Rep 13(5):282–285. doi:10.1007/BF00233320

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Robinson LE, Field CJ (1998) Dietary long-chain (n-3) fatty acids facilitate immune cell activation in sedentary, but not exercise-trained rats. J Nutr 128(3):498–504

    CAS  PubMed  Google Scholar 

  38. 38.

    Hoke EM, Maylock CA, Shacter E (2005) Desferal inhibits breast tumor growth and does not interfere with the tumoricidal activity of doxorubicin. Free Radic Biol Med 39(3):403–411. doi:10.1016/j.freeradbiomed.2005.03.029

    CAS  PubMed  Article  Google Scholar 

  39. 39.

    Marlind J, Kaspar M, Trachsel E, Sommavilla R, Hindle S, Bacci C, Giovannoni L, Neri D (2008) Antibody-mediated delivery of interleukin-2 to the stroma of breast cancer strongly enhances the potency of chemotherapy. Clin Cancer Res 14(20):6515–6524. doi:10.1158/1078-0432.CCR-07-5041

    CAS  PubMed  Article  Google Scholar 

  40. 40.

    North WG, Pang RH, Gao G, Memoli VA, Cole BF (2011) Native MAG-1 antibody almost destroys human breast cancer xenografts. Breast Cancer Res Treat 127(3):631–637. doi:10.1007/s10549-010-1009-6

    CAS  PubMed  Article  Google Scholar 

  41. 41.

    Field CJ, Ryan EA, Thomson AB, Clandinin MT (1988) Dietary fat and the diabetic state alter insulin binding and the fatty acyl composition of the adipocyte plasma membrane. Biochem J 253(2):417–424

    CAS  PubMed Central  PubMed  Google Scholar 

  42. 42.

    Folch J, Lees M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226(1):497–509

    CAS  PubMed  Google Scholar 

  43. 43.

    Schonberg S, Krokan HE (1995) The inhibitory effect of conjugated dienoic derivatives (CLA) of linoleic acid on the growth of human tumor cell lines is in part due to increased lipid peroxidation. Anticancer Res 15(4):1241–1246

    CAS  PubMed  Google Scholar 

  44. 44.

    Field CJ, Angel A, Clandinin MT (1985) Relationship of diet to the fatty acid composition of human adipose tissue structural and stored lipids. Am J Clin Nutr 42(6):1206–1220

    CAS  PubMed  Google Scholar 

  45. 45.

    Menendez JA, Ropero S, del Barbacid MM, Montero S, Solanas M, Escrich E, Cortes-Funes H, Colomer R (2002) Synergistic interaction between vinorelbine and gamma-linolenic acid in breast cancer cells. Breast Cancer Res Treat 72(3):203–219

    CAS  PubMed  Article  Google Scholar 

  46. 46.

    Barnhart BC, Alappat EC, Peter ME (2003) The CD95 type I/type II model. Semin Immunol 15(3):185–193

    CAS  PubMed  Article  Google Scholar 

  47. 47.

    Fulda S, Strauss G, Meyer E, Debatin KM (2000) Functional CD95 ligand and CD95 death-inducing signaling complex in activation-induced cell death and doxorubicin-induced apoptosis in leukemic T cells. Blood 95(1):301–308

    CAS  PubMed  Google Scholar 

  48. 48.

    Kim HS, Lee YS, Kim DK (2009) Doxorubicin exerts cytotoxic effects through cell cycle arrest and Fas-mediated cell death. Pharmacology 84(5):300–309. doi:10.1159/000245937

    CAS  PubMed  Article  Google Scholar 

  49. 49.

    Bernard-Gallon DJ, Vissac-Sabatier C, Antoine-Vincent D, Rio PG, Maurizis JC, Fustier P, Bignon YJ (2002) Differential effects of n-3 and n-6 polyunsaturated fatty acids on BRCA1 and BRCA2 gene expression in breast cell lines. Br J Nutr 87(4):281–289. doi:10.1079/BJNBJN2002522

    CAS  PubMed  Article  Google Scholar 

  50. 50.

    Biondo PD, Brindley DN, Sawyer MB, Field CJ (2008) The potential for treatment with dietary long-chain polyunsaturated n-3 fatty acids during chemotherapy. J Nutr Biochem 19(12):787–796. doi:10.1016/j.jnutbio.2008.02.003

    CAS  PubMed  Article  Google Scholar 

  51. 51.

    Schley PD, Brindley DN, Field CJ (2007) (n-3) PUFA alter raft lipid composition and decrease epidermal growth factor receptor levels in lipid rafts of human breast cancer cells. J Nutr 137(3):548–553

    CAS  PubMed  Google Scholar 

  52. 52.

    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 Res Treat 55(2):149–160

    CAS  PubMed  Article  Google Scholar 

  53. 53.

    Corsetto PA, Cremona A, Montorfano G, Jovenitti IE, Orsini F, Arosio P, Rizzo AM (2012) Chemical-physical changes in cell membrane microdomains of breast cancer cells after omega-3 PUFA incorporation. Cell Biochem Biophys 64(1):45–59. doi:10.1007/s12013-012-9365-y

    CAS  PubMed  Article  Google Scholar 

  54. 54.

    Kaur G, Cameron-Smith D, Garg M, Sinclair AJ (2011) Docosapentaenoic acid (22:5n-3): a review of its biological effects. Prog Lipid Res 50(1):28–34. doi:10.1016/j.plipres.2010.07.004

    CAS  PubMed  Article  Google Scholar 

  55. 55.

    Hunt DA, Lane HM, Zygmont ME, Dervan PA, Hennigar RA (2007) MRNA stability and overexpression of fatty acid synthase in human breast cancer cell lines. Anticancer Res 27(1A):27–34

    CAS  PubMed  Google Scholar 

  56. 56.

    Jin Q, Yuan LX, Boulbes D, Baek JM, Wang YN, Gomez-Cabello D, Hawke DH, Yeung SC, Lee MH, Hortobagyi GN, Hung MC, Esteva FJ (2010) Fatty acid synthase phosphorylation: a novel therapeutic target in HER2-overexpressing breast cancer cells. Breast Cancer Res 12(6):R96. doi:10.1186/bcr2777

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  57. 57.

    Menendez JA, Vellon L, Mehmi I, Oza BP, Ropero S, Colomer R, Lupu R (2004) Inhibition of fatty acid synthase (FAS) suppresses HER2/neu (erbB-2) oncogene overexpression in cancer cells. Proc Natl Acad Sci USA 101(29):10715–10720. doi:10.1073/pnas.0403390101

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  58. 58.

    Kunkel P, Ulbricht U, Bohlen P, Brockmann MA, Fillbrandt R, Stavrou D, Westphal M, Lamszus K (2001) Inhibition of glioma angiogenesis and growth in vivo by systemic treatment with a monoclonal antibody against vascular endothelial growth factor receptor-2. Cancer Res 61(18):6624–6628

    CAS  PubMed  Google Scholar 

  59. 59.

    Tsuji M, Murota SI, Morita I (2003) Docosapentaenoic acid (22:5, n-3) suppressed tube-forming activity in endothelial cells induced by vascular endothelial growth factor. Prostaglandins Leukot Essent Fatty Acids 68(5):337–342

    CAS  PubMed  Article  Google Scholar 

  60. 60.

    Bierer TL, Bui LM (2002) Improvement of arthritic signs in dogs fed green-lipped mussel (Perna canaliculus). J Nutr 132(6 Suppl 2):1634S–1636S

    CAS  PubMed  Google Scholar 

  61. 61.

    Rainsford KD, Whitehouse MW (1980) Gastroprotective and anti-inflammatory properties of green lipped mussel (Perna canaliculus) preparation. Arzneimittelforschung 30(12):2128–2132

    CAS  PubMed  Google Scholar 

  62. 62.

    Basu GD, Pathangey LB, Tinder TL, Lagioia M, Gendler SJ, Mukherjee P (2004) Cyclooxygenase-2 inhibitor induces apoptosis in breast cancer cells in an in vivo model of spontaneous metastatic breast cancer. Mol Cancer Res 2(11):632–642

    CAS  PubMed  Google Scholar 

  63. 63.

    Kundu N, Yang Q, Dorsey R, Fulton AM (2001) Increased cyclooxygenase-2 (cox-2) expression and activity in a murine model of metastatic breast cancer. Int J Cancer 93(5):681–686

    CAS  PubMed  Article  Google Scholar 

  64. 64.

    Rozic JG, Chakraborty C, Lala PK (2001) Cyclooxygenase inhibitors retard murine mammary tumor progression by reducing tumor cell migration, invasiveness and angiogenesis. Int J Cancer 93(4):497–506

    CAS  PubMed  Article  Google Scholar 

  65. 65.

    Harris WS, Lemke SL, Hansen SN, Goldstein DA, DiRienzo MA, Su H, Nemeth MA, Taylor ML, Ahmed G, George C (2008) Stearidonic acid-enriched soybean oil increased the omega-3 index, an emerging cardiovascular risk marker. Lipids 43(9):805–811. doi:10.1007/s11745-008-3215-0

    CAS  PubMed  Article  Google Scholar 

  66. 66.

    James MJ, Ursin VM, Cleland LG (2003) Metabolism of stearidonic acid in human subjects: comparison with the metabolism of other n-3 fatty acids. Am J Clin Nutr 77(5):1140–1145

    CAS  PubMed  Google Scholar 

  67. 67.

    Horia E, Watkins BA (2005) Comparison of stearidonic acid and alpha-linolenic acid on PGE2 production and COX-2 protein levels in MDA-MB-231 breast cancer cell cultures. J Nutr Biochem 16(3):184–192. doi:10.1016/j.jnutbio.2004.11.001

    CAS  PubMed  Article  Google Scholar 

  68. 68.

    Majumder PK, Pandey P, Sun X, Cheng K, Datta R, Saxena S, Kharbanda S, Kufe D (2000) Mitochondrial translocation of protein kinase C delta in phorbol ester-induced cytochrome c release and apoptosis. J Biol Chem 275(29):21793–21796. doi:10.1074/jbc.C000048200

    CAS  PubMed  Article  Google Scholar 

  69. 69.

    Mandil R, Ashkenazi E, Blass M, Kronfeld I, Kazimirsky G, Rosenthal G, Umansky F, Lorenzo PS, Blumberg PM, Brodie C (2001) Protein kinase Calpha and protein kinase Cdelta play opposite roles in the proliferation and apoptosis of glioma cells. Cancer Res 61(11):4612–4619

    CAS  PubMed  Google Scholar 

  70. 70.

    Larsson SC, Kumlin M, Ingelman-Sundberg M, Wolk A (2004) Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms. Am J Clin Nutr 79(6):935–945

    CAS  PubMed  Google Scholar 

  71. 71.

    Bernhardt G, Reile H, Birnbock H, Spruss T, Schonenberger H (1992) Standardized kinetic microassay to quantify differential chemosensitivity on the basis of proliferative activity. J Cancer Res Clin Oncol 118(1):35–43

    CAS  PubMed  Article  Google Scholar 

  72. 72.

    Hansen-Petrik MB, McEntee MF, Johnson BT, Obukowicz MG, Masferrer J, Zweifel B, Chiu CH, Whelan J (2002) Selective inhibition of Delta-6 desaturase impedes intestinal tumorigenesis. Cancer Lett 175(2):157–163

    CAS  PubMed  Article  Google Scholar 

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The authors acknowledge the technical support of Susan Goruk, Chris Kazala, and Robin Miles. Funding for this project came in part from the Canadian Institute of Health Sciences (CIHR) and in part from an investigator initiated grant to a provincial government agency Alberta Innovates Biosolutions (AIBS) that administered the funds to this project from their funding partner, the Alberta Canola Producers (ACP). RJW is grateful for the support provided by the Canada Research Chairs Program.

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The authors have no financial association with the owner of the patent or the funders of this project.

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Correspondence to C. J. Field.

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Subedi, K., Yu, HM., Newell, M. et al. Stearidonic acid-enriched flax oil reduces the growth of human breast cancer in vitro and in vivo. Breast Cancer Res Treat 149, 17–29 (2015).

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  • MDA-MB-231
  • MCF-7
  • MCF-12A
  • Mammary tumor
  • Polyunsaturated fatty acid
  • Phospholipids