Hostname: page-component-78c5997874-j824f Total loading time: 0 Render date: 2024-11-09T01:23:35.802Z Has data issue: false hasContentIssue false
  • English
  • Français

Conjugated linoleic acid (CLA)-enriched milk fat inhibits growth and modulates CLA-responsive biomarkers in MCF-7 and SW480 human cancer cell lines

Published online by Cambridge University Press:  09 March 2007

Áine Miller ,
Catherine Stanton ,
John Murphy  and
Rosaleen Devery
Áine Miller
Affiliation:
School of Biotechnology, Dublin City University, Dublin 9, Republic of Ireland
Catherine Stanton
Affiliation:
Teagasc Dairy Products Research Centre, Moorepark, Fermoy, Co. Cork, Republic of Ireland
John Murphy
Affiliation:
Teagasc Dairy Production Department, Moorepark, Fermoy, Co. Cork, Republic of Ireland
Rosaleen Devery*
Affiliation:
School of Biotechnology, National Institute of Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Republic of Ireland
*
*Corresponding author: Dr Rosaleen Devery, fax +353 1 7005412, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Milk enriched in conjugated linoleic acid (CLA) was obtained from cows on pasture supplemented with full-fat rapeseeds (FFR; 2·26g cis 9, trans 11 (c9, t11)-CLA/100g fatty acid methyl esters) and full-fat soyabeans (1·83g c9, t11-CLA/100g fatty acid methyl esters). A control milk fat (1·69g c9, t11-CLA/100g fatty acid methyl esters) was obtained from cows fed on pasture only. The present study assessed the potency of the CLA-enriched milk fats to modulate biomarkers that had previously been observed to respond to c9, t11-CLA in the MCF-7 and SW480 cell lines. Cell numbers decreased (P<0·05) by up to 61 and 58% following the incubation of MCF-7 and SW480 cells, respectively, for 4d with milk fats (yielding CLA concentrations between 60·2 and 80·6μM). The FFR milk fat, containing the highest CLA content, increased (P<0·05) [14C]arachidonic acid (AA) uptake into the monoacylglycerol fraction of MCF-7 and SW480 cells while it decreased (P<0·05) uptake into the phospholipid fraction of the latter. This milk fat also decreased (P<0·05) [14C]AA conversion to prostaglandin (PG) E2 while increasing conversion to PGF2α in both cell lines. All milk-fat samples increased (P<0·05) lipid peroxidation as measured by 8-epi-PGF2α in both cell lines. In SW480 cells the milk-fat samples decreased (P<0·05) bcl-2 and cytosolic glutathione levels while increasing (P<0·05) membrane-associated annexin V levels. All milk-fat samples decreased (P<0·05) the expression of ras in SW480 cells. These data suggest that milk-fat CLA was effective at modulating synthetic CLA-responsive biomarkers.

Keywords

Milk fatConjugated linoleic acidEicosanoidsApoptosis
Type
Research Article
Information
British Journal of Nutrition , Volume 90 , Issue 5 , November 2003 , pp. 877 - 885
Copyright
Copyright © The Nutrition Society 2003

References

Aro, A, Mannisto, S, Salminen, I, Ovaskainen, ML, Kataja, V & Uusitupa, M (2000) Inverse association between dietary and serum conjugated linoleic acid and risk of breast cancer in postmenopausal women. Nutr Cancer 38, 151–157.CrossRefGoogle ScholarPubMed
Belury, MA, Nickel, KP, Bird, CE & Wu, YM (1996) Dietary conjugated linoleic acid modulation of phorbol ester skin tumor promotion. Nutr Cancer 26, 149–157.CrossRefGoogle ScholarPubMed
Boland, M, MacGibbon, A & Hill, J (2001) Designer milks for the new millennium. Livest Prod Sci 72, 99–109.CrossRefGoogle Scholar
Calder, PC (2002) Conjugated linoleic acid in humans – reasons to be cheerful?. Curr Opin Clin Nutr Metab Care 5, 123–126.CrossRefGoogle ScholarPubMed
Campbell, SL, Khosravi-Far, R, Rossman, KL, Clark, GJ & Der, CJ (1998) Increasing complexity of Ras signaling. Oncogene 17, 1395–1413.CrossRefGoogle ScholarPubMed
Chilliard, Y, Ferlay, A & Doreau, M (2000) Effect of different types of forages, animal fat or marine oils in cow's diet on milk fat secretion and composition, especially conjugated linoleic acid (CLA) and polyunsaturated fatty acids. Livest Prod Sci 70, 31–48.CrossRefGoogle Scholar
Chin, SF, Liu, W, Storkson, JM, Ha, YL & Pariza, MW (1992) Dietary sources of conjugated dienoic isomers of linoleic acid, a newly recognised class of anticarcinogens. J Food Comp Anal 5, 185–197.CrossRefGoogle Scholar
Geiser, AG, Anderson, MJ & Stanbridge, EJ (1989) Suppression of tumorigenicity in human cell hybrids derived from cell lines expressing different activated ras oncogenes. Cancer Res 49, 1572–1577.Google ScholarPubMed
Gibbs, JB, Oliff, A & Kohl, NE (1994) Farnesyltransferase inhibitors: Ras research yields a potential cancer therapeutic. Cell 77, 175–178.CrossRefGoogle ScholarPubMed
Griinari, JM, Corl, BA, Lacy, SH, Chouinard, PY, Nurmela, KV & Bauman, DE (2000) Conjugated linoleic acid is synthesized endogenously in lactating dairy cows by Delta(9)-desaturase. J Nutr 130, 2285–2291.CrossRefGoogle ScholarPubMed
Ha, YL, Storkson, J & Pariza, MW (1990) Inhibition of benzo(a)pyrene-induced mouse forestomach neoplasia by conjugated dienoic derivatives of linoleic acid. Cancer Res 50, 1097–1101.Google ScholarPubMed
Hissin, PJ & Hilf, R (1976) A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal Biochem 74, 214–226.CrossRefGoogle ScholarPubMed
Ip, C, Banni, S & Angioni, E (1999) Conjugated linoleic acid-enriched butter fat alters mammary gland morphogenesis and reduces cancer risk in rats. J Nutr 129, 2135–2142.CrossRefGoogle ScholarPubMed
Ip, C, Briggs, SP, Haegele, AD, Thompson, HJ, Storkson, J & Scimeca, JA (1996) The efficacy of conjugated linoleic acid in mammary cancer prevention is independent of the level or type of fat in the diet. Carcinogenesis 17, 1045–1050.CrossRefGoogle ScholarPubMed
Ip, C, Dong, Y, Thompson, HJ, Bauman, DE & Ip, MM (2001) Control of rat mammary epithelium proliferation by conjugated linoleic acid. Nutr Cancer 39, 233–238.CrossRefGoogle ScholarPubMed
Ip, C, Singh, M, Thompson, HJ & Scimeca, JA (1994) Conjugated linoleic acid suppresses mammary carcinogenesis and proliferative activity of the mammary gland in the rat. Cancer Res 54, 1212–1215.Google ScholarPubMed
Jarvinen, R, Knekt, P, Hakulinen, T & Aromaa, A (2001) Prospective study on milk products, calcium and cancers of the colon and rectum. Eur J Clin Nutr 55, 1000–1007.CrossRefGoogle ScholarPubMed
Kepler, CR & Tove, SB (1967) Biohydrogenation of unsaturated fatty acids. J Biol Chem 242, 5686–5692.CrossRefGoogle ScholarPubMed
Knekt, P, Jarvinen, R, Seppanen, R, Pukkala, E & Aromaa, A (1996) Intake of dairy products and the risk of breast cancer. Br J Cancer 73, 687–691.CrossRefGoogle ScholarPubMed
Laemmli, UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T 4. Nature 227, 680–685.CrossRefGoogle Scholar
Lawless, F, Murphy, JJ, Harrington, D, Devery, R & Stanton, C (1998) Elevation of conjugated cis-9, trans-11-octadecadienoic acid in bovine milk because of dietary supplementation. J Dairy Sci 81, 3259–3267.CrossRefGoogle ScholarPubMed
Liew, C, Schut, HAJ, Chin, SF, Pariza, MW & Dashwood, RH (1995) Protection of conjugated linoleic acids against 2-amino-3-methylimidazo[4,5-f]quinoline-induced colon carcinogenesis in the F344 rat – a study of inhibitory mechanisms. Carcinogenesis 16, 3037–3043.CrossRefGoogle ScholarPubMed
Lopaczynski, W & Zeisel, SH (2001) Antioxidants, programme cell death and cancer. Nutr Res 21, 295–307.CrossRefGoogle Scholar
McGrath, E, Stanton, C & Devery, R (2001) Conjugated linoleic acid isomers inhibit ras expression in the SW480 colon cancer cell line. Ir J Agric Food Res 41, 144.Google Scholar
Miller, A, McGrath, E, Stanton, C & Devery, R (2003) Vaccenic acid (t11–18:1) is converted to conjugated linoleic acid (c9, t11-CLA) in MCF-7 and SW480 cancer cells. Lipids 38, 623–632.CrossRefGoogle ScholarPubMed
Miller, A, Stanton, C & Devery, R (2001) Modulation of arachidonic acid distribution by conjugated linoleic acid isomers and linoleic acid in MCF-7 and SW480 cancer cells. Lipids 36, 1161–1168.CrossRefGoogle ScholarPubMed
Miller, A, Stanton, C & Devery, R (2002) Cis 9, trans 11- and trans 10, cis 12 conjugated linoleic acid isomers induce apoptosis in cultured SW480 cells. Anticancer Res 22, 3879–3888.Google ScholarPubMed
Milner, JA (1999) Functional foods and health promotion. J Nutr 129, 1395S–1397S.CrossRefGoogle ScholarPubMed
O'Shea, M, Stanton, C & Devery, R (1999) Antioxidant enzyme defence responses of human MCF-7 and SW480 cancer cells to conjugated linoleic acid. Anticancer Res 19, 1953–1959.Google ScholarPubMed
O'Shea, M, Stanton, C & Devery, R (2000) Milk fat conjugated linoleic acid (CLA) inhibits growth of human mammary MCF-7 cancer cells. Anticancer Res 20, 3591–3601.Google ScholarPubMed
Palombo, JD, Ganguly, A, Bistrian, BR & Menard, MP (2002) The antiproliferative effects of biologically active isomers of conjugated linoleic acid on human colorectal and prostatic cancer cells. Cancer Lett 177, 163–172.CrossRefGoogle ScholarPubMed
Park, Y, Allen, KG & Shultz, TD (2000) Modulation of MCF-7 breast cancer cell signal transduction by linoleic acid and conjugated linoleic acid in culture. Anticancer Res 20, 669–676.Google ScholarPubMed
Ritzenthaler, KL, McGuire, MK, Falen, R, Shultz, TD, Dasgupta, N & McGuire, MA (2001) Estimation of conjugated linoleic acid intake by written dietary assessment methodologies underestimates actual intake evaluated by food duplicate methodology. J Nutr 131, 1548–1554.CrossRefGoogle ScholarPubMed
Tang, DG, Li, L, Zhu, ZY & Joshi, B (1998) Apoptosis in the absence of cytochrome c accumulation in the cytosol. Biochem Biophys Res Commun 242, 380–384.CrossRefGoogle ScholarPubMed
Towbin, H, Staehelin, T & Gordon, J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76, 4350–4354.CrossRefGoogle ScholarPubMed
Waslidge, NB & Hayes, DJ (1995) A colorimetric method for the determination of lipoxygenase activity suitable for use in a high throughput assay format. Anal Biochem 231, 354–358.CrossRefGoogle Scholar
Watkins, MT, Patton, GM & Soler, HM (1999) Synthesis of 8-epi-prostaglandin F 2α by human endothelial cells: role of prostaglandin H 2 synthase. Biochem J 344, 747–754.CrossRefGoogle Scholar
Zhou, JR & Blackburn, GL (1999) Dietary lipid modulation of immune responses in tumorigenesis. In Nutritional Oncology pp. 195–213[Heber, GL, Blackburn, D and Go, VLW, editors]. San Diego, CA: Academic Press.Google Scholar