Hostname: page-component-586b7cd67f-r5fsc Total loading time: 0 Render date: 2024-11-20T06:30:42.407Z Has data issue: false hasContentIssue false
  • English
  • Français

Growth inhibitory effects of casein hydrolysates on human cancer cell lines

Published online by Cambridge University Press:  07 January 2010

Martha Phelan ,
S. Aisling Aherne ,
Dara O'Sullivan ,
Richard J. FitzGerald  and
Nora M. O'Brien
Martha Phelan
Affiliation:
Department of Food and Nutritional Sciences, University College Cork, Cork, Ireland
S. Aisling Aherne
Affiliation:
Department of Food and Nutritional Sciences, University College Cork, Cork, Ireland
Dara O'Sullivan
Affiliation:
Department of Life Sciences, University of Limerick, Limerick, Ireland
Richard J. FitzGerald
Affiliation:
Department of Life Sciences, University of Limerick, Limerick, Ireland
Nora M. O'Brien*
Affiliation:
Department of Food and Nutritional Sciences, University College Cork, Cork, Ireland
*
*For correspondence; e-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

The aim of this study was to investigate the effects of unhydrolysed/intact casein and eight different sodium casein hydrolysates (a–h) on the viability and growth of human cancer cell lines. Both human Jurkat T cells and Caco-2 cells were incubated with increasing concentrations of the test compounds (0·5–10% v/v) for 24 h. Cell viability was assessed using the MTT, lactate dehydrogenase (LDH) release and Trypan Blue assays. Cell growth was monitored using the MTT, Trypan Blue and Bromodeoxyuridine (BrdU) proliferation assays. Casein hydrolysates b, c and f had an inhibitory effect on the viability and growth of both cell lines. The casein hydrolysates did not negatively affect the membrane integrity of both Jurkat and Caco-2 cells. In Jurkat cells hydrolysates a and h had an inhibitory effect on DNA synthesis after 24 h, while in Caco-2 cells DNA synthesis was not affected. In conclusion, we found that the different casein hydrolysates had cell-specific effects which target particular functions within the cell. Overall, casein hydrolysates had no effect on membrane integrity while they had varied effects on mitochondrial activity and DNA synthesis in the different cell lines.

Keywords

Casein hydrolysatesCaco-2 cellsJurkat cellsgrowthviability
Type
Research Article
Information
Journal of Dairy Research , Volume 77 , Issue 2 , May 2010 , pp. 176 - 182
Copyright
Copyright © Proprietors of Journal of Dairy Research 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aras, MA, Hartnett, KA & Aizenman, E 2008 Assessment of cell viability in primary neuronal cultures. Current Protocols in Neuroscience 44 1–7CrossRefGoogle Scholar
Azuma, N, Nagaune, S, Ishino, Y, Mori, H, Kaminogawa, S & Yamauchi, K 1989 DNA-synthesis stimulating peptides from human β-casein. Agricultural Biological Chemistry 53 2631–2634Google Scholar
Cameron, L 1990 Colon carcinogenesis: modulation of progression. In Colon Cancer Cells, pp. 74 (Eds Moyer, MP & Poste, GH). New York, USA: Academic Press, Inc. New YorkGoogle Scholar
Ciapetti, G, Cenni, E, Pratelli, L & Pizzoferrato, A 1993 In vitro evaluation of cell/biomaterial interaction by MTT assay. Biomaterials 14 359–364CrossRefGoogle ScholarPubMed
Durrieu, C, Degraeve, P, Carnet-Pantiez, A & Martial, A 2005 Assessment of the immunomodulatory activity of cheese extracts by a complete and easy to handle in vitro screening methodology. Biotechnology Letters 27 969–975CrossRefGoogle ScholarPubMed
Elion, EA 2001 The Ste5p scaffold. Journal of Cell Science 114 3967–3978CrossRefGoogle ScholarPubMed
FitzGerald, RJ & Meisel, H 2003 Milk protein hydrolysates and bioactive peptides. In Advanced Dairy Chemistry: Proteins1A, pp. 675–698 (Eds Fox, PF & McSweeney, PLH). New York: Kluwer Academic/Plenum PressCrossRefGoogle Scholar
Flanagan, J & FitzGerald, RJ 2002 Functionality of Bacillus proteinase hydrolysates of sodium caseinate. International Dairy Journal 12 737–748CrossRefGoogle Scholar
Gülden, M & Seibert, H 2003 In vitro-in vivo extrapolation: estimation of human serum concentrations of chemicals equivalent to cytotoxic concentrations in vitro. Toxicology 189 211–222CrossRefGoogle ScholarPubMed
Hagiwara, T, Shinoda, I, Fukuwatari, Y & Shimamura, S 1995 Effects of lactoferrin and its peptides on proliferation of rat intestinal epithelial cell line IEC-18, in the presence of epithelial growth factor. Bioscience, Biotechnology and Biochemistry 59 1875–1881CrossRefGoogle Scholar
Hartmann, R & Meisel, H 2004 Caseinophosphopeptides and their cell modulting potential. Biofactors 21 73–78CrossRefGoogle Scholar
Hartmann, R, Wal, J-M, Bernard, H & Pentzien, A-K 2007 Cytotoxic and allergenic potential of bioactive proteins and peptides. Current Pharmaceutical Design 13 897–920CrossRefGoogle ScholarPubMed
IDF 20-2 2001 Milk: determination of nitrogen content. Part 2: Block digestion (macro) method. Brussels, Belgium: International Dairy FederationGoogle Scholar
Jing, H & Kitts, DD 2004 Redox-related cytotoxic responses to different casein glycation products in Caco-2 and Int-407 cells. Journal of Agricultural and Food Chemistry 52 3577–3582CrossRefGoogle ScholarPubMed
Koh, YJ & Choi, DW 1987 Quantitive determination of glutamate-mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay. Journal of Neuroscience Methods 20 83–90CrossRefGoogle ScholarPubMed
Korhonen, H & Pihlanto, A 2006 Bioactive peptides: production and functionality. International Dairy Journal 16 975–960CrossRefGoogle Scholar
Korhonen, H & Pihlanto-Leppälä, A 2001 Milk protein-derived bioactive peptides-novel opportunities for health promotion. International Dairy Federation Bulletin 363 17–26Google Scholar
Laparra, JM, Alegría, A, Barberá, R & Farré, R 2008 Antioxidant effect of casein phosphopeptides compared with fruit beverages supplemented with skimmed milk against H2O2-induced oxidative stress in Caco-2 cells. Food Research International 41 773–779Google Scholar
MacDonald, R, Thornton, WH & Marshall, R 1994 A cell culture model to identify biologically active peptides generated by bacterial hydrolysis of casein. Journal Dairy Science 77 1167–1175CrossRefGoogle ScholarPubMed
Meisel, H & FitzGerald, RJ 2003 Biofunctional peptides from milk proteins: mineral binding and cytomodulatory effects. Current Pharmaceutical Design 9 1289–1295Google ScholarPubMed
Meisel, H & Günther, S 1998 Food proteins as precursors of peptides modulating human cell activity. Nahrung 42 175–1763.0.CO;2-R>CrossRefGoogle ScholarPubMed
Meisel, H & Schlimme, E 1996 Bioactive peptides derived from milk proteins – ingredients for functional foods? Kieler Milch Forsch 48 343–357Google Scholar
Mosmann, T 1983 Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods 65 55–63CrossRefGoogle ScholarPubMed
Motobu, M, El-Abasy, M, Na, KJ & Hirota, Y 2002 Detection of mitogen induced lymphocyte proliferation by bromodeoxyuridine (BrdU) incorporation in the chicken. The Journal of Vetinerary Medicine Science 64 377–379Google ScholarPubMed
Phelan, M, Aherne-Bruce, SA, O'Sullivan, D, FitzGerald, RJ & O'Brien, NM 2009 Potential bioactive effects of casein hydrolysates on human cultured cells. International Dairy Journal 19 279–285CrossRefGoogle Scholar
Phelan, M, Aherne, SA, FitzGerald, RJ & O'Brien, NM 2009 Casein-derived bioactive peptides: Biological effects, industrial uses, safety aspects and regulatory status. International Dairy Journal 19 643–654CrossRefGoogle Scholar
Ramos-Mandujano, G, Weiss-Steidera, B, Meloa, B, Córdovaa, Y, Ledesma-Martíneza, E, Bustos, S, Silvestre, O, Aguiňiga, I, Sosa, N, Martínez, I, Sánchez, L, García, A & Santiago-Osorio, E 2008 Alpha-, beta- and kappa-caseins inhibit the proliferation of the myeloid cell lines 32D cl3 and WEHI-3 and exhibit different differentiation properties. Immunobiology 213 133–141Google Scholar
Ringseis, R, Matthes, B, Lehmann, V, Becker, K, Schöps, R, Ulbrich-Hofmann, R & Eder, K 2005 Peptides and hydrolysates from casein and soy protein modulate the release of vasoactive substances from human aortic endothelial cells. Biochimica et Biophysica Acta 1721 89–97CrossRefGoogle ScholarPubMed
Roy, MK, Wantanabe, Y & Tamai, Y 1999 Induction of apoptosis in HL-60 cells by skimmed milk digested with a proteolytic enzyme from the yeast Saccharomyces cerevisiae. Journal of Bioscience and Bioengineering 88 426–432CrossRefGoogle ScholarPubMed
van't Veer, PJ, Dekker, M, Lamers, JWJ, Kok, FJ, Schouten, EG, Brants, HAM, Sturmans, F & Hermus, JJ 1989 Consumption of fermented milk products and breast cancer: a case-control study in the Netherlands. Cancer Research 49 4020–4023Google ScholarPubMed
Wright, SC, Zhong, J & Larrick, JW 1994 Inhibition of apoptosis as a mechanism of tumor promotion. FASEB Journal 8 654–660CrossRefGoogle ScholarPubMed