Lipids

, Volume 44, Issue 3, pp 249–256

Inhibitory Effect of Conjugated α-Linolenic Acid from Bifidobacteria of Intestinal Origin on SW480 Cancer Cells

  • Mairéad Coakley
  • Sebastiano Banni
  • Mark C. Johnson
  • Susan Mills
  • Rosaleen Devery
  • Gerald Fitzgerald
  • R. Paul Ross
  • Catherine Stanton
Original Article

Abstract

In this study, we assessed the ability of six strains of bifidobacteria (previously shown by us to possess the ability to convert linoleic acid to c9, t11-conjugated linoleic acid (CLA) to grow in the presence of α-linolenic acid and to generate conjugated isomers of the fatty acid substrate during fermentation for 42 h. The six strains of bifidobacteria were grown in modified MRS (mMRS) containing α-linolenic acid for 42 h at 37 °C, after which the fatty acid composition of the growth medium was assessed by gas liquid chromatography (GLC). Indeed, following fermentation of one of the strains, namely Bifidobacterium breve NCIMB 702258, in the presence of 0.41 mg/ml α-linolenic acid, 79.1% was converted to the conjugated isomer, C18:3 c9, t11, c15 conjugated α-linolenic acid (CALA). To examine the inhibitory effect of the fermented oils produced, SW480 colon cancer cells were cultured in the presence of the extracted fermented oil (10–50 μg/ml) for 5 days. The data indicate an inhibitory effect on cell growth (p ≤ 0.001) of CALA, with cell numbers reduced by 85% at a concentration of 180 μM, compared with a reduction of only 50% with α-linolenic acid (p ≤ 0.01).

Keywords

Bifidobacterium α-Linolenic acid Conjugated α-linolenic acid (CALA) Cancer Health promotion 

References

  1. 1.
    Dupertuis YM, Meguid MM, Pichard C (2007) Colon cancer therapy: new perspectives of nutritional manipulations using polyunsaturated fatty acids. Curr Opin Clin Nutr Metab Care 10:427–432PubMedCrossRefGoogle Scholar
  2. 2.
    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 79:935–945PubMedGoogle Scholar
  3. 3.
    Destaillats F, Trottier JP, Galvez JM, Angers P (2005) Analysis of alpha-linolenic acid biohydrogenation intermediates in milk fat with emphasis on conjugated linolenic acids. J Dairy Sci 88:3231–3239PubMedCrossRefGoogle Scholar
  4. 4.
    Miller A, Stanton C, Murphy J, Devery R (2003) Conjugated linoleic acid (CLA)-enriched milk fat inhibits growth and modulates CLA-responsive biomarkers in MCF-7 and SW480 human cancer cell lines. Br J Nutr 90:877–885PubMedCrossRefGoogle Scholar
  5. 5.
    Bhattacharya A, Banu J, Rahman M, Causey J, Fernandes G (2006) Biological effects of conjugated linoleic acids in health and disease. J Nutr Biochem 17:789–810PubMedCrossRefGoogle Scholar
  6. 6.
    Ip C, Dong Y, Ip MM, Banni S, Carta G, Angioni G, Murru E, Spada S, Melis MP, Saebo A (2002) Conjugated linoleic acid isomers and mammary cancer prevention. Nutr Cancer 43:52–58PubMedCrossRefGoogle Scholar
  7. 7.
    Belury MA (2002) Inhibition of carcinogenesis by conjugated linoleic acid: potential mechanisms of action. J Nutr 132:2995–2998PubMedGoogle Scholar
  8. 8.
    Wang YW, Jones PJ (2004) Conjugated linoleic acid and obesity control: efficacy and mechanisms. Int J Obes Relat Metab Disord 28:941–955PubMedCrossRefGoogle Scholar
  9. 9.
    Terpstra AHM (2004) Effect of conjugated linoleic acid on body composition and plasma lipids in humans. Amer J Clin Nutr 79:352–361PubMedGoogle Scholar
  10. 10.
    Kritchevsky D, Tepper SA, Wright S, Tso P, Czarnecki SK (2000) Influence of conjugated linoleic acid (CLA) on establishment and progression of atherosclerosis in rabbits. J Am Coll Nutr 19:472S–477SPubMedGoogle Scholar
  11. 11.
    Nicolosi RJ, Rogers EJ, Kritchevsky D, Scimeca JA, Huth PJ (1997) Dietary conjugated linoleic acid reduces plasma lipoproteins and early aortic atherosclerosis in hypercholesterolemic hamsters. Artery 22:266–277PubMedGoogle Scholar
  12. 12.
    Nagao K, Yanagita T (2005) Conjugated fatty acids in food and their health benefits. J Biosci Bioeng 100:152–157PubMedCrossRefGoogle Scholar
  13. 13.
    Yasui Y, Hosokawa M, Kohno H, Tanaka T, Myashita K (2006) Growth inhibition and apoptosis induction by all-trans-conjugated linolenic acids on human colon cancer cells. Anticancer Res 26:1855–1860PubMedGoogle Scholar
  14. 14.
    Yasui Y, Hosokawa M, Sahara T, Suzuki R, Ohgiya S, Kohno H, Tanaka T, Miyashita K (2005) Bitter gourd seed fatty acid rich in 9c, 11t, 13t-conjugated linolenic acid induces apoptosis and up-regulates the GADD45, p53 and PPARγ in human colon cancer Caco-2 cells. Prostaglandins Leukot Essent Fatty Acids 73:113–119PubMedCrossRefGoogle Scholar
  15. 15.
    Tsuzuki T, Tokuyama Y, Igarashi M, Miyazawa T (2004) Tumor growth suppression by α-eleostearic acid, a linolenic acid isomer with a conjugated triene system, via lipid peroxidation. Carcinogenesis 25:1417–1425PubMedCrossRefGoogle Scholar
  16. 16.
    Yasui Y, Hosokawa M, Kohno H, Tanaka T, Miyashita K (2006) Troglitazone and 9cis, 11trans, 13trans-conjugated linolenic acid: comparison of their antiproliferative and apoptosis-inducing effects on different colon cancer cell lines. Chemotherapy 52:220–225PubMedCrossRefGoogle Scholar
  17. 17.
    Arao K, Yotsumoto H, Han SY, Nagao K, Yanagita T (2004) The 9cis, 11trans, 13cis isomer of conjugated linolenic acid reduces apoliprotein B100 secretion and triacylglycerol synthesis in HepG2 cells. Biosci Biotechnol Biochem 68:2643–2645PubMedCrossRefGoogle Scholar
  18. 18.
    Futakuchi M, Cheng JL, Hirose M, Kimoto N, Cho YM, Iwata T, Kasai M, Tokudome S, Shirai T (2002) Inhibition of conjugated fatty acids derived from safflower or perilla oil of induction and development of mammary tumors in rats induced by 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP). Cancer Lett 178:131–139PubMedCrossRefGoogle Scholar
  19. 19.
    Coakley M, Ross RP, Nordgren M, Fitzgerald G, Devery R, Stanton C (2003) Conjugated linoleic acid biosynthesis by human-derived Bifidobacterium species. J Appl Microbiol 94:138–145PubMedCrossRefGoogle Scholar
  20. 20.
    Coakley M, Johnson MC, McGrath E, Rahman S, Ross RP, Fitzgerald GF, Devery R, Stanton C (2006) Intestinal bifidobacteria that produce trans-9, trans-11 CLA: a fatty acid with anti-proliferative activity against human colon SW480 and HT-29 cancer cells. Nutr Cancer 56:95–102PubMedCrossRefGoogle Scholar
  21. 21.
    Rosberg-Cody E, Ross RP, Hussey S, Ryan CA, Murphy BP, Fitzgerald GF, Devery R, Stanton C (2004) Mining the microbiota of the neonatal gastrointestinal tract for conjugated linoleic acid-producing bifidobacteria. Appl Environ Microbiol 70:4635–4641PubMedCrossRefGoogle Scholar
  22. 22.
    Melis MP, Angioni E, Carta G, Murru E, Scannu P, Spada S, Banni S (2001) Characterisation of conjugated linoleic acid and its metabolites by RP-HPLC with diode array detector. Eur J Lipid Sci Technol 103:617–621CrossRefGoogle Scholar
  23. 23.
    Banni S, Day BW, Evans RW, Corongiu FP, Lombardi B (1995) Detection of conjugated diene fatty acid isomers in liver lipids of rats fed a choline devoid diet indicates that the diet does not cause lipid peroxidation. J Nutr Biochem 6:281–289CrossRefGoogle Scholar
  24. 24.
    Barrett E, Ross RP, Fitzgerald GF, Stanton C (2007) Rapid screening method for analyzing the conjugated linoleic acid production capabilities of bacterial cultures. Appl Environ Microbiol 73:2333–2337PubMedCrossRefGoogle Scholar
  25. 25.
    Angioni E, Lercker G, Frega NG, Carta G, Melis MP, Murru E, Spada S, Banni S (2002) UV spectral properties of lipids as a tool for their identification. Eur J Lipid Sci Technol 104:59–64CrossRefGoogle Scholar
  26. 26.
    Fritsche JRR, Steinhart H (1999) Formation, contents and estimation of daily intake of conjugated linoleic acid isomers and trans-fatty acids in foods. Adv Conjugated Linoleic Acid Res 1:378–396Google Scholar
  27. 27.
    Leahy S, Higgins D, Fitzgerald GF, van Sinderen D (2005) Getting better with bifidobacteria. J Appl Microbiol 98:1303–1315PubMedCrossRefGoogle Scholar
  28. 28.
    Picard C, Fioramonti J, Francois A, Robinson T, Neant F, Matuchansky C (2005) Review article: bifidobacteria as probiotic agents—physiological effects and clinical benefits. Aliment Pharmacol Ther 22:495–512PubMedCrossRefGoogle Scholar
  29. 29.
    Suzuki R, Yasui Y, Kohno H, Miyamoto S, Hosokawa M, Miyashita K, Tanaka T (2006) Catalpa seed oil rich in 9t, 11t, 13c-conjugated linolenic acid suppresses the development of colonic aberrant crypt foci induced by azoxymethane in rats. Oncol Rep 16:989–996PubMedGoogle Scholar
  30. 30.
    Chuang C-Y, Hsu C, Chao C, Wein Y-S, Kuo Y-H, Huang C (2006) Fractionation and identification of 9c, 11t, 13t-conjugated linolenic acid as an activator of PPARα in bitter gourd (Momordica charantia L.). J Biomed Sci 13:763–772PubMedCrossRefGoogle Scholar
  31. 31.
    Ogawa J, Kishino S, Ando A, Sugimoto S, Mihara K, Shimizu S (2005) Production of conjugated fatty acids by lactic acid bacteria. J Biosc Bioeng 100:355–364CrossRefGoogle Scholar
  32. 32.
    Vonk RJ, Kalivianakis M, Minich DM, Biijleveld CM, Verade HJ (1997) The metabolic importance of unabsorbed dietary lipids in the colon. Scand J Gastroenterol 222:65–67Google Scholar
  33. 33.
    Hill MJ (1998) Composition and control of ileal contents. Eur J Cancer Prev 7:S75–S78PubMedCrossRefGoogle Scholar
  34. 34.
    Plourde M, Destaillats F, Chouinard PY, Angers P (2007) Conjugated alpha-linolenic acid isomers in bovine milk and muscle. J Dairy Sci 90:5269–5275PubMedCrossRefGoogle Scholar
  35. 35.
    Rise P, Eligini S, Ghezzi S, Colli S, Galli C (2007) Fatty acid composition of plasma, blood cells and whole blood: relevance for the assessment of the fatty acid status in humans. Prostaglandins Leukot Essent Fatty Acids 76:363–369PubMedCrossRefGoogle Scholar
  36. 36.
    Biavati B, Vescovo M, Torriani S, Bottazzi V (2000) Bifidobacteria: history, ecology, physiology and applications. Ann Microbiol 50:117–131Google Scholar
  37. 37.
    Matsuki T, Watanabe K, Tanaka R (2003) Genus- and species-specific PCR primers for the detection and identification of bifidobacteria. Curr Issues Intest Microbiol 4:61–69PubMedGoogle Scholar
  38. 38.
    Gueimonde M, Debor L, Tolkko S, Jokisalo E, Salminen S (2007) Quantitative assessment of faecal bifidobacterial populations by real-time PCR using lanthanide probes. J Appl Microbiol 102:1116–1122PubMedGoogle Scholar
  39. 39.
    Barrett E, Ross RP, Fitzgerald GF, Stanton C (2007) Rapid screening method for analyzing the conjugated linoleic acid production capabilities of bacterial cultures. Appl Environ Microbiol 73:2333–2337PubMedCrossRefGoogle Scholar
  40. 40.
    Dinoto A, Marques TM, Sakamoto K, Fukiya S, Watanabe J, Ito S, Yokota A (2006) Population dynamics of Bifidobacterium species in human feces during raffinose administration monitored by fluorescence in situ hybridization-flow cytometry. Appl Environ Microbiol 72:7739–7747PubMedCrossRefGoogle Scholar
  41. 41.
    Kelley NS, Hubbard NE, Erickson KL (2007) Conjugated linoleic acid isomers and cancer. J Nutr 137:2599–2607PubMedGoogle Scholar
  42. 42.
    Esterbauer H (1993) Cytotoxicity and genotoxicity of lipid oxidation products. Am J Clin Nutr 57:779S–786SPubMedGoogle Scholar
  43. 43.
    Sandstorm PA, Tebbey PW, Van Cleave S, Buttke TM (1994) Lipid hydroperoxides induce apoptosis in T cells displaying a HIV-associated glutathione peroxidase deficiency. J Biol Chem 269:798–801Google Scholar
  44. 44.
    Aoshima H, Satoh T, Sakai N, Yamada M, Enokiko Y, Ikeuchi T, Hatanaka H (1997) Generation of free radicals during lipid hydroperoxide-triggered apoptosis in PC12 h cells. Biochim Biophys Acta 1345:35–42PubMedGoogle Scholar
  45. 45.
    Ji C, Rouzer CA, Marnett LJ, Pietenpol JA (1998) Induction of cell cycle arrest by the endogenous product of lipid peroxidation, malondialdehyde. Carcinogenesis 19:1275–1283PubMedCrossRefGoogle Scholar
  46. 46.
    Gupta RA, Dubois RN (2002) PPARγ as a target for treatment of colorectal cancer. Am J Physiol 283:G266–G269Google Scholar
  47. 47.
    Sporn MB, Suh N, Mangelsdorf DJ (2001) Prospects for prevention and treatment of cancer with selective PPARγ modulators (SPARMS). Trends Mol Med 7:395–400PubMedCrossRefGoogle Scholar
  48. 48.
    Tsuzuki T, Kawakami Y, Abe R, Nakagawa K, Koba K, Imamura J, Iwata T, Ikeda I, Miyazawa T (2006) Conjugated linolenic acid is slowly absorbed in rat intestine, but quickly converted to conjugated linoleic acid. J Nutr 136:2153–2159PubMedGoogle Scholar

Copyright information

© AOCS 2008

Authors and Affiliations

  • Mairéad Coakley
    • 1
  • Sebastiano Banni
    • 4
  • Mark C. Johnson
    • 1
  • Susan Mills
    • 1
    • 2
  • Rosaleen Devery
    • 3
  • Gerald Fitzgerald
    • 2
  • R. Paul Ross
    • 1
    • 2
  • Catherine Stanton
    • 1
    • 2
  1. 1.Teagasc, Biotechnology CentreMoorepark Food Research CentreFermoyIreland
  2. 2.Alimentary Pharmabiotic CentreUniversity CollegeCorkIreland
  3. 3.National Institute for Cellular BiotechnologyDublin City UniversityDublinIreland
  4. 4.Dipartimento di Biologia Sperimentale, Università degli Studi di CagliariCittadella UniversitariaMonserratoItaly

Personalised recommendations