Breast Cancer Research and Treatment

, Volume 101, Issue 1, pp 7–16 | Cite as

Differential Effects of Omega-3 and Omega-6 fatty Acids on Gene Expression in Breast Cancer Cells

  • Rasha Hammamieh
  • Nabarun Chakraborty
  • Stacy-Ann Miller
  • Edward Waddy
  • Mohsen Barmada
  • Rina Das
  • Sheila A. Peel
  • Agnes A. Day
  • Marti JettEmail author


Essential fatty acids have long been identified as possible oncogenic factors. Existing reports suggest omega-6 (ω-6) essential fatty acids (EFA) as pro-oncogenic and omega-3 (ω-3) EFA as anti-oncogenic factors. The ω-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), inhibit the growth of human breast cancer cells while the ω-6 fatty acids induces growth of these cells in animal models and cell lines. In order to explore likely mechanisms for the modulation of breast cancer cell growth by ω-3 and ω-6 fatty acids, we examined the effects of arachidonic acid (AA), linoleic Acid (LA), EPA and DHA on human breast cancer cell lines using cDNA microarrays and quantitative polymerase chain reaction. MDA-MB-231, MDA-MB-435s, MCF-7 and HCC2218 cell lines were treated with the selected fatty acids for 6 and 24 h. Microarray analysis of gene expression profiles in the breast cancer cells treated with both classes of fatty acids discerned essential differences among the two classes at the earlier time point. The differential effects of ω-3 and ω-6 fatty acids on the breast cancer cells were lessened at the late time point. Data mining and statistical analyses identified genes that were differentially expressed between breast cancer cells treated with ω-3 and ω-6 fatty acids. Ontological investigations have associated those genes to a broad spectrum of biological functions, including cellular nutrition, cell division, cell proliferation, metastasis and transcription factors etc., and thus presented an important pool of biomarkers for the differential effect of ω-3 and ω-6EFAs.


Arachidonic acid (AA) Eicosapentaenoic acid (EPA) DNA microarray N-3 polyunsaturated fatty acid N-6 polyunsaturated fatty acid 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.



This work is partially funded by a grant from the US Army Medical Research and Materiel Command, award number DAMD-17-01-1-0268


  1. 1.
    Apantaku LM (2000) Breast cancer diagnosis and screening. Am Fam Physician 62(3):596–602, 605–606Google Scholar
  2. 2.
    Apantaku LM (2002) Breast-conserving surgery for breast cancer. Am Fam Physician 66(12): 2271–2278PubMedGoogle Scholar
  3. 3.
    Carroll KK (1985) Dietary fat in relation to mammary carcinogenesis. Princess Takamatsu Symp 16:255–263PubMedGoogle Scholar
  4. 4.
    Enig MG, Munn RJ, Keeney M (1978) Dietary fat and cancer trends–a critique. Fed Proc 37(9):2215–2220PubMedGoogle Scholar
  5. 5.
    Hilakivi-Clarke L, Olivo SE, Shajahan A, Khan G, Zhu Y, Zwart A, Cho E, Clarke R (2005) Mechanisms mediating the effects of prepubertal (n–3) polyunsaturated fatty acid diet on breast cancer risk in rats. J Nutr 135(12 Suppl):2946S–2952SPubMedGoogle Scholar
  6. 6.
    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):187–195PubMedCrossRefGoogle Scholar
  7. 7.
    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):340–348PubMedCrossRefGoogle Scholar
  8. 8.
    Cohen LA (1997) Breast cancer risk in rats fed a diet high in n–6 polyunsaturated fatty acids during pregnancy. J Natl Cancer Inst 89(9):662–663PubMedCrossRefGoogle Scholar
  9. 9.
    Lanson M, Bougnoux P, Besson P, Lansac J, Hubert B, Couet C, Le Floch O (1990) N–6 polyunsaturated fatty acids in human breast carcinoma phosphatidylethanolamine and early relapse. Br J Cancer 61(5):776–778PubMedGoogle Scholar
  10. 10.
    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):199–212PubMedCrossRefGoogle Scholar
  11. 11.
    Karmali RA (1989) n–3 fatty acids and cancer. J Intern Med Suppl 731:197–200PubMedGoogle Scholar
  12. 12.
    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):219–227PubMedGoogle Scholar
  13. 13.
    Hammamieh R, Chakraborty N, Das R, Jett M (2004) Molecular impacts of antisense complementary to the liver fatty acid binding protein (FABP) mRNA in DU 145 prostate cancer cells in vitro. J Exp Ther Oncol 4(3):195–202PubMedGoogle Scholar
  14. 14.
    Esmon CT (2003) The protein C pathway. Chest 124(3 Suppl):26S–32SPubMedCrossRefGoogle Scholar
  15. 15.
    Yin Y, Liu YX, Jin YJ, Hall EJ, Barrett JC (2003) PAC1 phosphatase is a transcription target of p53 in signalling apoptosis and growth suppression. Nature 422(6931): 527–531PubMedCrossRefGoogle Scholar
  16. 16.
    Germani A, Prabel A, Mourah S, Podgorniak MP, Di Carlo A, Ehrlich R, Gisselbrecht S, Varin-Blank N, Calvo F, Bruzzoni-Giovanelli H (2003) SIAH-1 interacts with CtIP and promotes its degradation by the proteasome pathway. Oncogene 22(55):8845–8851PubMedCrossRefGoogle Scholar
  17. 17.
    Chiyo M, Shimozato O, Yu L, Kawamura K, Iizasa T, Fujisawa T, Tagawa M (2005) Expression of IL-27 in murine carcinoma cells produces antitumor effects and induces protective immunity in inoculated host animals. Int J Cancer 115(3):437–442PubMedCrossRefGoogle Scholar
  18. 18.
    Zhang Y, Pasparakis M, Kollias G, Simons M (1999) Myocyte-dependent regulation of endothelial cell syndecan-4 expression. Role of TNF-alpha. J Biol Chem 274(21):14,786–14,790CrossRefGoogle Scholar
  19. 19.
    Lee BP, Rushlow WJ, Chakraborty C, Lala PK (2001) Differential gene expression in premalignant human trophoblast: role of IGFBP-5. Int J Cancer 94(5):674–684PubMedCrossRefGoogle Scholar
  20. 20.
    Jensen LE, Whitehead AS (2003) Expression of alternatively spliced interleukin-1 receptor accessory protein mRNAs is differentially regulated during inflammation and apoptosis. Cell Signal 15(8):793–802PubMedGoogle Scholar
  21. 21.
    Nagahata T, Sato T, Tomura A, Onda M, Nishikawa K, Emi M (2005) Identification of RAI3 as a therapeutic target for breast cancer. Endocr Relat Cancer 12(1):65–73PubMedCrossRefGoogle Scholar
  22. 22.
    Pigott DA, Grimaldi MA, Dell’Aquila ML, Gaffney EV (1982) Growth inhibitors in plasma derived human serum. In Vitro 18(7):617–625PubMedGoogle Scholar
  23. 23.
    Cardoso F, Ross JS, Picart MJ, Sotiriou C, Durbecq V (2004) Targeting the ubiquitin-proteasome pathway in breast cancer. Clin Breast Cancer 5(2):148–157PubMedCrossRefGoogle Scholar
  24. 24.
    Cloitre M, Heimberg RG, Holt CS, Liebowitz MR (1992) Reaction time to threat stimuli in panic disorder and social phobia. Behav Res Ther 30(6):609–617PubMedCrossRefGoogle Scholar
  25. 25.
    Dennis JW, Laferte S, Yagel S, Breitman ML (1989) Asparagine-linked oligosaccharides associated with metastatic cancer. Cancer Cells 1(3):87–92PubMedGoogle Scholar
  26. 26.
    Xiang Q, Fan SQ, Li J, Tan C, Xiang JJ, Zhang QH, Wang R, Li GY (2002) [Expression of connexin43 and connexin45 in nasopharyngeal carcinoma]. Ai Zheng 21(6):593–596PubMedGoogle Scholar
  27. 27.
    Hodgson JG, Malek T, Bornstein S, Hariono S, Ginzinger DG, Muller WJ, Gray JW (2005) Copy number aberrations in mouse breast tumors reveal loci and genes important in tumorigenic receptor tyrosine kinase signaling. Cancer Res 65(21):9695–9704PubMedCrossRefGoogle Scholar
  28. 28.
    Yokozaki H, Budillon A, Tortora G, Meissner S, Beaucage SL, Miki K, Cho-Chung YS (1993) An antisense oligodeoxynucleotide that depletes RI alpha subunit of cyclic AMP-dependent protein kinase induces growth inhibition in human cancer cells. Cancer Res 53(4):868–872PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • Rasha Hammamieh
    • 1
  • Nabarun Chakraborty
    • 1
  • Stacy-Ann Miller
    • 1
  • Edward Waddy
    • 1
  • Mohsen Barmada
    • 1
  • Rina Das
    • 1
  • Sheila A. Peel
    • 2
  • Agnes A. Day
    • 3
  • Marti Jett
    • 1
    Email author
  1. 1.Division of PathologyWalter Reed Army Institute of ResearchSilver SpringUSA
  2. 2.Division of RetrovirologyWalter Reed Army Institute of ResearchRockvilleUSA
  3. 3.Microbiology DepartmentHoward University College of MedicineWashington, DCUSA

Personalised recommendations