The toxicity of bovine α-lactalbumin made lethal to tumor cells is highly dependent on oleic acid and induces killing in cancer cell lines and noncancer-derived primary cells

FEBS Journal

Volumn 278, Issue 11, 2011, Pages 1955-1967

  Brinkmann, Christel Rothe ^a   Heegaard, Christian Würtz ^a   Petersen, Torben Ellebãk ^a   Jensenius, Jens Christian ^a   Thiel, Steffen ^a  

^a AARHUS UNIVERSITY   (Denmark)

Author keywords

lactalbumin; BAMLET; cytotoxicity; fatty acid; oleic acid

Indexed keywords

7 AMINODACTINOMYCIN; ADENOSINE TRIPHOSPHATE; ALPHA LACTALBUMIN; BOVINE ALPHA LACTALBUMIN OLEIC ACID COMPLEX; CAMPTOTHECIN; CYTOTOXIC AGENT; LIPOCORTIN 5; OLEIC ACID; PHOSPHATIDYLSERINE; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; B LYMPHOCYTE; CANCER CELL CULTURE; CELL DEATH; CELL VIABILITY; CONTROLLED STUDY; CYTOLYSIS; DOSE RESPONSE; DRUG CYTOTOXICITY; ERYTHROCYTE; FLOW CYTOMETRY; HUMAN; HUMAN CELL; LEUKEMIA CELL LINE; MONOCYTE; NATURAL KILLER CELL; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; PROTEIN BINDING; T LYMPHOCYTE; TUMOR CELL;

ANIMALS; APOPTOSIS; CATTLE; CELL LINE, TUMOR; ERYTHROCYTES; LACTALBUMIN; OLEIC ACID;

BOVINAE;

EID: 79956211956     PISSN: 1742464X     EISSN: 17424658     Source Type: Journal    
DOI: 10.1111/j.1742-4658.2011.08112.x     Document Type: Article

References (47)

1. Svanborg C, Agerstam H, Aronson A, Bjerkvig R, Düringer C, Fischer W, Gustafsson L, Hallgren O, Leijonhuvud I, Linse S, et al., (2003) HAMLET kills tumor cells by an apoptosis-like mechanism-cellular, molecular, and therapeutic aspects. Adv Cancer Res 88, 1-29. (Pubitemid 36343277)
2. Svensson M, HÃkansson A, Mossberg AK, Linse S, &, Svanborg C, (2000) Conversion of alpha-lactalbumin to a protein inducing apoptosis. Proc Natl Acad Sci USA 97, 4221-4226. (Pubitemid 30226114)
3. Pettersson J, Mossberg AK, &, Svanborg C, (2006) alpha-Lactalbumin species variation, HAMLET formation, and tumor cell death. Biochem Biophys Res Commun 345, 260-270.
4. Fischer W, Gustafsson L, Mossberg AK, Gronli J, Mork S, Bjerkvig R, &, Svanborg C, (2004) Human alpha-lactalbumin made lethal to tumor cells (HAMLET) kills human glioblastoma cells in brain xenografts by an apoptosis-like mechanism and prolongs survival. Cancer Res 64, 2105-2112. (Pubitemid 38339460)
5. Mossberg AK, Hou Y, Svensson M, Holmqvist B, &, Svanborg C, (2010) HAMLET treatment delays bladder cancer development. J Urol 183, 1590-1597.
6. Gustafsson L, Leijonhufvud I, Aronsson A, Mossberg AK, &, Svanborg C, (2004) Treatment of skin papillomas with topical alpha-lactalbumin-oleic acid. N Engl J Med 350, 2663-2672.
7. Mossberg AK, Wullt B, Gustafsson L, MÃnsson W, Ljunggren E, &, Svanborg C, (2007) Bladder cancers respond to intravesical instillation of HAMLET (human alpha-lactalbumin made lethal to tumor cells). Int J Cancer 121, 1352-1359. (Pubitemid 47293805)
8. Pettersson-Kastberg J, Mossberg AK, Trulsson M, Yong YJ, Min S, Lim Y, O'Brien JE, Svanborg C, &, Mok KH, (2009) alpha-Lactalbumin, engineered to be nonnative and inactive, kills tumor cells when in complex with oleic acid: a new biological function resulting from partial unfolding. J Mol Biol 394, 994-1010.
9. Liskova K, Kelly AL, O'Brien N, &, Brodkorb A, (2010) Effect of denaturation of alpha-lactalbumin on the formation of BAMLET (bovine alpha-lactalbumin made lethal to tumor cells). J Agric Food Chem 58, 4421-4427.
10. Tolin S, De Franceschi G, Spolaore B, Frare E, Canton M, Polverino de Laureto P, &, Fontana A, (2010) The oleic acid complexes of proteolytic fragments of alpha-lactalbumin display apoptotic activity. FEBS J 277, 163-173.
11. Wilhelm K, Darinskas A, Noppe W, Duchardt E, Mok KH, Vukojevic V, Schleucher J, &, Morozova-Roche LA, (2009) Protein oligomerization induced by oleic acid at the solid-liquid interface-equine lysozyme cytotoxic complexes. FEBS J 276, 3975-3989.
12. Vukojevic V, Bowen AM, Wilhelm K, Ming Y, Ce Z, Schleucher J, Hore PJ, Terenius L, &, Morozova-Roche LA, (2010) Lipoprotein complex of equine lysozyme with oleic acid (ELOA) interactions with the plasma membrane of live cells. Langmuir 26, 14782-14787.
13. Spolaore B, Pinato O, Canton M, Zambonin M, Polverino de Laureto P, &, Fontana A, (2010) alpha-Lactalbumin forms with oleic acid a high molecular weight complex displaying cytotoxic activity. Biochemistry 49, 8658-8667.
14. Pettersson-Kastberg J, Aits S, Gustafsson L, Mossberg A, Storm P, Trulsson M, Persson F, Hun Mok K, &, Svanborg C, (2009) Can misfolded proteins be beneficial? The HAMLET case. Ann Med 41, 162-176.
15. Fast J, Mossberg AK, Nilsson H, Svanborg C, Akke M, &, Linse S, (2005) Compact oleic acid in HAMLET. FEBS Lett 579, 6095-6100. (Pubitemid 41546253)
16. Brinkmann CR, Thiel S, Larsen MK, Petersen TE, Jensenius JC, &, Heegaard CW, (2011) Preparation and comparison of cytotoxic complexes formed between oleic acid and either bovine or human alpha-lactalbumin. J Dairy Sci, in press, doi:10.3168/jds.2010-3622.
17. Svensson M, Mossberg AK, Pettersson J, Linse S, &, Svanborg C, (2003) Lipids as cofactors in protein folding: stereo-specific lipid-protein interactions are required to form HAMLET (human alpha-lactalbumin made lethal to tumor cells). Protein Sci 12, 2805-2814. (Pubitemid 37445104)
18. Thompson MP, Farrell HM, Mohanam S, Liu S, Kidwell WR, Bansal MP, Cook RG, Medina D, Kotts CE, &, Bano M, (1992) Identification of human-milk alpha-lactalbumin as a cell-growth inhibitor. Protoplasma 167, 134-144.
19. Sternhagen LG, &, Allen JC, (2001) Growth rates of a human colon adenocarcinoma cell line are regulated by the milk protein alpha-lactalbumin. Adv Exp Med Biol 501, 115-120. (Pubitemid 34102186)
20. Xu M, Sugiura Y, Nagaoka S, &, Kanamaru Y, (2005) IEC-6 intestinal cell death induced by bovine milk alpha-lactalbumin. Biosci Biotechnol Biochem 69, 1082-1089. (Pubitemid 41006936)
21. Xu M, Sugiura Y, Nagaoka S, &, Kanamaru Y, (2005) Involvement of SDS-stable higher M(r) forms of bovine normal milk alpha-lactalbumin in inducing intestinal IEC-6 cell death. Biosci Biotechnol Biochem 69, 1189-1192. (Pubitemid 41006949)
22. Kamijima T, Ohmura A, Sato T, Akimoto K, Itabashi M, Mizuguchi M, Kamiya M, Kikukawa T, Aizawa T, Takahashi M, et al., (2008) Heat-treatment method for producing fatty acid-bound alpha-lactalbumin that induces tumor cell death. Biochem Biophys Res Commun 376, 211-214.
23. Lin IC, Su SL, &, Kuo CD, (2008) Induction of cell death in RAW 264.7 cells by alpha-lactalbumin. Food Chem Toxicol 46, 842-853.
24. Riley LG, Wynn PC, Williamson P, &, Sheehy PA, (2008) The role of native bovine alpha-lactalbumin in bovine mammary epithelial cell apoptosis and casein expression. J Dairy Res 75, 319-325.
25. van Engeland M, Nieland LJ, Ramaekers FC, Schutte B, &, Reutelingsperger CP, (1998) Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry 31, 1-9. (Pubitemid 28050057)
26. Falzone N, Huyser C, &, Franken DR, (2010) Comparison between propidium iodide and 7-amino-actinomycin-D for viability assessment during flow cytometric analyses of the human sperm acrosome. Andrologia 42, 20-26.
27. Casbarra A, Birolo L, Infusini G, Dal Piaz F, Svensson M, Pucci P, Svanborg C, &, Marino G, (2004) Conformational analysis of HAMLET, the folding variant of human alpha-lactalbumin associated with apoptosis. Protein Sci 13, 1322-1330. (Pubitemid 38526097)
28. Hallgren O, Gustafsson L, Irjala H, Selivanova G, Orrenius S, &, Svanborg C, (2006) HAMLET triggers apoptosis but tumor cell death is independent of caspases, Bcl-2 and p53. Apoptosis 11, 221-233. (Pubitemid 43291022)
29. Düringer C, Hamiche A, Gustafsson L, Kimura H, &, Svanborg C, (2003) HAMLET interacts with histones and chromatin in tumor cell nuclei. J Biol Chem 278, 42131-42135. (Pubitemid 37310480)
30. Baltzer A, Svanborg C, &, Jaggi R, (2004) Apoptotic cell death in the lactating mammary gland is enhanced by a folding variant of alpha-lactalbumin. Cell Mol Life Sci 61, 1221-1228. (Pubitemid 38703751)
31. Gustafsson L, Hallgren O, Mossberg AK, Pettersson J, Fischer W, Aronsson A, &, Svanborg C, (2005) HAMLET kills tumor cells by apoptosis: structure, cellular mechanisms, and therapy. J Nutr 135, 1299-1303. (Pubitemid 40638352)
32. Fast J, Mossberg AK, Svanborg C, &, Linse S, (2005) Stability of HAMLET-a kinetically trapped alpha-lactalbumin oleic acid complex. Protein Sci 14, 329-340. (Pubitemid 40194584)
33. HÃkansson A, Zhivotovsky B, Orrenius S, Sabharwal H, &, Svanborg C, (1995) Apoptosis induced by a human milk protein. Proc Natl Acad Sci USA 92, 8064-8068.
34. Knyazeva EL, Grishchenko VM, Fadeev RS, Akatov VS, Permyakov SE, &, Permyakov EA, (2008) Who Is Mr HAMLET? Interaction of human alpha-lactalbumin with monomeric oleic acid Biochemistry 47, 13127-13137.
35. Mossberg AK, Puchades M, Halskau O, Baumann A, Lanekoff I, Chao Y, Martinez A, Svanborg C, &, Karlsson R, (2010) HAMLET interacts with lipid membranes and perturbs their structure and integrity. PLoS ONE 5, e9384.
36. Martins de Lima T, Cury-Boaventura MF, Giannocco G, Nunes MT, &, Curi R, (2006) Comparative toxicity of fatty acids on a macrophage cell line (J774). Clin Sci 111, 307-317. (Pubitemid 44690189)
37. Andrade LN, de Lima TM, Curi R, &, Castrucci AM, (2005) Toxicity of fatty acids on murine and human melanoma cell lines. Toxicol In Vitro 19, 553-560.
38. Cury-Boaventura MF, Gorjao R, de Lima TM, Newsholme P, &, Curi R, (2006) Comparative toxicity of oleic and linoleic acid on human lymphocytes. Life Sci 78, 1448-1456. (Pubitemid 43233812)
39. Aits S, Gustafsson L, Hallgren O, Brest P, Gustafsson M, Trulsson M, Mossberg AK, Simon HU, Mograbi B, &, Svanborg C, (2009) HAMLET (human alpha-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death. Int J Cancer 124, 1008-1019.
40. Köhler C, Gogvadze V, HÃkansson A, Svanborg C, Orrenius S, &, Zhivotovsky B, (2001) A folding variant of human alpha-lactalbumin induces mitochondrial permeability transition in isolated mitochondria. Eur J Biochem 268, 186-191. (Pubitemid 32052263)
41. Gustafsson L, Aits S, Onnerfjord P, Trulsson M, Storm P, &, Svanborg C, (2009) Changes in proteasome structure and function caused by HAMLET in tumor cells. PLoS ONE 4, e5229.
42. Rammer P, Groth-Pedersen L, Kirkegaard T, Daugaard M, Rytter A, Szyniarowski P, Hoyer-Hansen M, Povlsen LK, Nylandsted J, Larsen JE, et al., (2010) BAMLET activates a lysosomal cell death program in cancer cells. Mol Cancer Ther 9, 24-32.
43. Galluzzi L, Aaronson SA, Abrams J, Alnemri ES, Andrews DW, Baehrecke EH, Bazan NG, Blagosklonny MV, Blomgren K, Borner C, et al., (2009) Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes. Cell Death Differ 16, 1093-1107.
44. Erikstrup C, Pedersen LM, Heickendorff L, Ledet T, &, Rasmussen LM, (2001) Production of hyaluronan and chondroitin sulphate proteoglycans from human arterial smooth muscle-the effect of glucose, insulin, IGF-I or growth hormone. Eur J Endocrinol 145, 193-198. (Pubitemid 32707606)
45. Ostergaard L, Stankevicius E, Andersen MR, Eskildsen-Helmond Y, Ledet T, Mulvany MJ, &, Simonsen U, (2007) Diminished NO release in chronic hypoxic human endothelial cells. Am J Physiol Heart Circ Physiol 293, H2894-H2903. (Pubitemid 350106513)
46. Kragballe K, Desjarlais L, &, Voorhees JJ, (1985) Leukotrienes B4, C4 and D4 stimulate DNA synthesis in cultured human epidermal keratinocytes. Br J Dermatol 113, 43-52. (Pubitemid 15006910)
47. Kronman MJ, &, Andreotti RE, (1964) Inter- and intramolecular interactions of alpha-lactalbumin. I. The apparent heterogeneity at acid pH. Biochemistry 3, 1145-1151.