Lipids as tumoricidal components of human α-lactalbumin made lethal to tumor cells (HAMLET): Unique and shared effects on signaling and death

Journal of Biological Chemistry

Volumn 288, Issue 24, 2013, Pages 17460-17471

  Ho, James C S ^a   Storm, Petter ^a   Rydström, Anna ^a   Bowen, Ben ^b   Alsin, Fredrik ^a,b   Sullivan, Louise ^c   Ambite, Inès ^a   Mok, K H ^c   Northen, Trent ^b   Svanborg, Catharina ^a  

^a LUND UNIVERSITY   (Sweden)

^b LAWRENCE BERKELEY NATIONAL LABORATORY   (United States)

^c TRINITY COLLEGE DUBLIN   (Ireland)

Author keywords

[No Author keywords available]

Indexed keywords

CELL MEMBRANES; CELL PROLIFERATION; CYTOLOGY; GENE EXPRESSION; METABOLITES; OLEIC ACID; PROTEINS; TUMORS;

ALPHA-LACTALBUMIN; CELLULAR INTERACTION; CELLULAR RESPONSE; CYTOPLASMIC MEMBRANE; EXTRACELLULAR PROTEINS; LONG CHAIN FATTY ACID; NATURAL ABUNDANCE; UNFOLDED PROTEINS;

CELL SIGNALING;

ANTINEOPLASTIC AGENT; HUMAN ALPHA LACTALBUMIN MADE LETHAL TO TUMOR CELL; OLEIC ACID; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CELL DEATH; CELL INTERACTION; CELL VIABILITY; COMPLEX FORMATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG EFFECT; GENE EXPRESSION REGULATION; GENETIC ASSOCIATION; HOST CELL; ION CURRENT; LIPID ANALYSIS; PRIORITY JOURNAL; PROTEIN UNFOLDING; PROTON TRANSPORT; SIGNAL TRANSDUCTION; UPREGULATION;

EID: 84879064652     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.468405     Document Type: Article

References (58)

1. Larsson, S. C., Kumlin, M., Ingelman-Sundberg, M., and 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, 935-945 (Pubitemid 41095944)
2. Amri, E. Z., Bertrand, B., Ailhaud, G., and Grimaldi, P. (1991) Regulation of adipose cell differentiation. I. Fatty acids are inducers of the aP2 gene expression. J. Lipid Res. 32, 1449-1456
3. Anderson, M. P., and Welsh, M. J. (1990) Fatty acids inhibit apical membrane chloride channels in airway epithelia. Proc. Natl. Acad. Sci. U.S.A. 87, 7334-7338
4. Grimaldi, P. A., Knobel, S. M., Whitesell, R. R., and Abumrad, N. A. (1992) Induction of aP2 gene expression by nonmetabolized long-chain fatty acids. Proc. Natl. Acad. Sci. U.S.A. 89, 10930-10934
5. Distel, R. J., Robinson, G. S., and Spiegelman, B. M. (1992) Fatty acid regulation of gene expression. Transcriptional and post-transcriptional mechanisms. J. Biol. Chem. 267, 5937-5941
6. Bhatt, A. P., Jacobs, S. R., Freemerman, A. J., Makowski, L., Rathmell, J. C., Dittmer, D. P., and Damania, B. (2012) Dysregulation of fatty acid synthesis and glycolysis in non-Hodgkin lymphoma. Proc. Natl. Acad. Sci. U.S.A. 109, 11818-11823
7. Hotamisligil, G. S. (2006) Inflammation and metabolic disorders. Nature 444, 860-867
8. Das, U. N. (2005) Long-chain polyunsaturated fatty acids, endothelial lipase, and atherosclerosis. Prostaglandins Leukot. Essent. Fatty Acids 72, 173-179
9. Calder, P. C. (1997) n-3 polyunsaturated fatty acids and cytokine production in health and disease. Ann. Nutr. Metab. 41, 203-234
10. Pohl, J., Ring, A., Ehehalt, R., Schulze-Bergkamen, H., Schad, A., Verkade, P., and Stremmel, W. (2004) Long-chain fatty acid uptake into adipocytes depends on lipid raft function. Biochemistry 43, 4179-4187 (Pubitemid 38445638)
11. Covey, S. D., Brunet, R. H., Gandhi, S. G., McFarlane, N., Boreham, D. R., Gerber, G. E., and Trigatti, B. L. (2007) Cholesterol depletion inhibits fatty acid uptake without affecting CD36 or caveolin-1 distribution in adipocytes. Biochem. Biophys. Res. Commun. 355, 67-71 (Pubitemid 46273367)
12. Hajri, T., and Abumrad, N. A. (2002) Fatty acid transport across membranes. Relevance to nutrition and metabolic pathology. Annu. Rev. Nutr. 22, 383-415 (Pubitemid 35221466)
13. Håkansson, A., Zhivotovsky, B., Orrenius, S., Sabharwal, H., and Svanborg, C. (1995) Apoptosis induced by a human milk protein. Proc. Natl. Acad. Sci. U.S.A. 92, 8064-8068
14. Svensson, M., Håkansson, A., Mossberg, A. K., Linse, S., and Svanborg, C. (2000) Conversion of α-lactalbumin to a protein inducing apoptosis. Proc. Natl. Acad. Sci. U.S.A. 97, 4221-4226 (Pubitemid 30226114)
15. Svanborg, C., Agerstam, H., Aronson, A., Bjerkvig, R., Düringer, C., Fischer, W., Gustafsson, L., Hallgren, O., Leijonhuvud, I., Linse, S., Mossberg, A.-K., Nilsson, H., Pettersson, J., and Svensson, M. (2003) HAMLET kills tumor cells by an apoptosis-like mechanism. Cellular, molecular, and therapeutic aspects. Adv. Cancer Res. 88, 1-29 (Pubitemid 36343277)
16. Fischer, W., Gustafsson, L., Mossberg, A.-K., Gronli, J., Mork, S., Bjerkvig, R., and Svanborg, C. (2004) Human α-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)
17. Gustafsson, L., Leijonhufvud, I., Aronsson, A., Mossberg, A.-K., and Svanborg, C. (2004) Treatment of Skin Papillomas with Topical α-Lactalbumin-Oleic Acid. N. Engl. J. Med. 350, 2663-2672
18. Mossberg, A.-K., Hou, Y., Svensson, M., Holmqvist, B., and Svanborg, C. (2010) HAMLET treatment delays bladder cancer development. J. Urol. 183, 1590-1597
19. Mossberg, A.-K., Wullt, B., Gustafsson, L., Månsson, W., Ljunggren, E., and Svanborg, C. (2007) Bladder cancers respond to intravesical instillation of HAMLET (human α-lactalbumin made lethal to tumor cells). Int. J. Cancer 121, 1352-1359 (Pubitemid 47293805)
20. Puthia, M., Storm, P., Nadeem, A., Hsiung, S., and Svanborg, C. (2013) Prevention and treatment of colon cancer by peroral administration of HAMLET (human α-lactalbumin made lethal to tumour cells). Gut 0, 1-12
21. Aits, S., Gustafsson, L., Hallgren, O., Brest, P., Gustafsson, M., Trulsson, M., Mossberg, A.-K., Simon, H.-U., Mograbi, B., and Svanborg, C. (2009) HAMLET (human α-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death. Int. J. Cancer 124, 1008-1019
22. Storm, P., Aits, S., Puthia, M. K., Urbano, A., Northen, T., Powers, S., Bowen, B., Chao, Y., Reindl, W., Lee, D. Y., Sullivan, N. L., Zhang, J., Trulsson, M., Yang, H., Watson, J. D., and Svanborg, C. (2011) Conserved features of cancer cells define their sensitivity to HAMLET-induced death. c-Myc and glycolysis. Oncogene 30, 4765-4779
23. Storm, P., Klausen, T. K., Trulsson, M., Ho CS, J., Dosnon, M., Westergren, T., Chao, Y., Rydström, A., Yang, H., Pedersen, S. F., and Svanborg, C. (2013) A unifying mechanism for tumor cell death by ion channel activation. Plos ONE 8, e58578
24. Gustafsson, L., Aits, S., Onnerfjord, P., Trulsson, M., Storm, P., and Svanborg, C. (2009) Changes in proteasome structure and function caused by HAMLET in tumor cells. PLoS One 4, e5229
25. Düringer, C., Hamiche, A., Gustafsson, L., Kimura, H., and Svanborg, C. (2003) HAMLET interacts with histones and chromatin in tumor cell nuclei. J. Biol. Chem. 278, 42131-42135 (Pubitemid 37310480)
26. Svensson, M., Mossberg, A.-K., Pettersson, J., Linse, S., and Svanborg, C. (2003) Lipids as cofactors in protein folding. Stereo-specific lipid-protein interactions are required to form HAMLET (human α-lactalbumin made lethal to tumor cells). Protein Sci. 12, 2805-2814 (Pubitemid 37445104)
27. Lisková, K., Kelly, A. L., O'Brien, N., and Brodkorb, A. (2010) Effect of denaturation of α-lactalbumin on the formation of BAMLET (bovine α-lactalbumin made lethal to tumor cells). J. Agric. Food Chem. 58, 4421-4427
28. Permyakov, S. E., Knyazeva, E. L., Khasanova, L. M., Fadeev, R. S., Zhadan, A. P., Roche-Hakansson, H., Håkansson, A. P., Akatov, V. S., and Permyakov, E. A. (2012) Oleic acid is a key cytotoxic component of HAMLET-like complexes. Biol. Chem. 393, 85-92
29. Vukojević, V., Bowen, A. M., Wilhelm, K., Ming, Y., Ce, Z., Schleucher, J., Hore, P. J., Terenius, L., and Morozova-Roche, L. A. (2010) Lipoprotein complex of equine lysozyme with oleic acid (ELOA) interactions with the plasma membrane of live cells. Langmuir 26, 14782-14787
30. Tolin, S., De Franceschi, G., Spolaore, B., Frare, E., Canton, M., Polverino de Laureto, P., and Fontana, A. (2010) The oleic acid complexes of proteolytic fragments of α-lactalbumin display apoptotic activity. FEBS J. 277, 163-173
31. Cistola, D. P., Hamilton, J. A., Jackson, D., and Small, D. M. (1988) Ionization and phase behavior of fatty acids in water. Application of the Gibbs phase rule. Biochemistry 27, 1881-1888
32. Kanicky, J. R., and Shah, D. O. (2002) Effect of degree, type, and position of unsaturation on the pKa of long-chain fatty acids. J. Colloid Interface Sci. 256, 201-207 (Pubitemid 36164593)
33. Lišková, K., Auty, M. A. E., Chaurin, V., Min, S., Mok, K. H., O'Brien, N., Kelly, A. L., and Brodkorb, A. (2011) Cytotoxic complexes of sodium oleate with β-lactoglobulin. Eur. J. Lipid Sci. Technol. 113, 1207-1218
34. Louis-Jeune, C., Andrade-Navarro, M. A., and Perez-Iratxeta, C. (2011) Prediction of protein secondary structure from circular dichroism using theoretically derived spectra. Proteins 80, 374-381
35. Schnars, U., and Jüptner, W. (2005) Digital Holography: Digital Hologram Recording, Numerical Reconstruction, and Related Techniques, Springer, Berlin
36. Gustafsson, M., Sebesta, M., Bengtsson, B., Pettersson, S. G., Egelberg, P., and Lenart, T. (2004) High-resolution digital transmission microscopy. A Fourier holography approach. Opt. Lasers Eng. 41, 553-563
37. Cuche, E., Bevilacqua, F., and Depeursinge, C. (1999) Digital holography for quantitative phase-contrast imaging. Opt. Lett. 24, 291-293 (Pubitemid 129571880)
38. Sebesta, M., and Gustafsson, M. (2005) Object characterization with refractometric digital Fourier holography. Opt. Lett. 30, 471-473 (Pubitemid 40339484)
39. Dubois, F., Yourassowsky, C., Monnom, O., Legros, J. C., Debeir, O., Van Ham, P., Kiss, R., and Decaestecker, C. (2006) Digital holographic microscopy for the three-dimensional dynamic analysis of in vitro cancer cell migration. J. Biomed. Opt. 11, 054032
40. Irizarry, R. A., Bolstad, B. M., Collin, F., Cope, L. M., Hobbs, B., and Speed, T. P. (2003) Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res. 31, e15
41. Dennis, G., Jr., Sherman, B. T., Hosack, D. A., Yang, J., Gao, W., Lane, H. C., and Lempicki, R. A. (2003) DAVID. Database for annotation, visualization, and integrated discovery. Genome Biol. 4, P3
42. Nozaka, M., Kuwajima, K., Nitta, K., and Sugai, S. (1978) Detection and characterization of the intermediate on the folding pathway of human α-lactalbumin. Biochemistry 17, 3753-3758 (Pubitemid 9022585)
43. Permyakov, E. A., Morozova, L. A., and Burstein, E. A. (1985) Cation binding effects on the pH, thermal, and urea denaturation transitions in α-lactalbumin. Biophys. Chem. 21, 21-31
44. Brest, P., Gustafsson, M., Mossberg, A.-K., Gustafsson, L., Duringer, C., Hamiche, A., and Svanborg, C. (2007) Histone deacetylase inhibitors promote the tumoricidal effect of HAMLET. Cancer Research 67, 11327-11334 (Pubitemid 350248559)
45. Pettersson, J., Mossberg, A. K., and Svanborg, C. (2006) α-Lactalbumin species variation, HAMLET formation, and tumor cell death. Biochem. Biophys. Res. Commun. 345, 260-270
46. Pettersson-Kastberg, J., Aits, S., Gustafsson, L., Mossberg, A., Storm, P., Trulsson, M., Persson, F., Mok, K. H., and Svanborg, C. (2009) Can misfolded proteins be beneficial? The HAMLET case. Ann. Med. 41, 162-176
47. Wilhelm, K., Darinskas, A., Noppe, W., Duchardt, E., Mok, K. H., Vukojević, V., Schleucher, J., and Morozova-Roche, L. A. (2009) Protein oligomerization induced by oleic acid at the solid-liquid interface. Equine lysozyme cytotoxic complexes. FEBS J. 276, 3975-3989
48. Baumann, A., Gjerde, A. U., Ying, M., Svanborg, C., Holmsen, H., Glomm, W. R., Martinez, A., and Halskau, O. (2012) HAMLET forms annular oligomers when deposited with phospholipid monolayers. J. Mol. Biol. 418, 90-102
49. Mossberg, A.-K., Puchades, M., Halskau, Ø., Baumann, A., Lanekoff, I., Chao, Y., Martinez, A., Svanborg, C., and Karlsson, R. (2010) HAMLET interacts with lipid membranes and perturbs their structure and integrity. PLoS One 5, e9384
50. Zherelova, O. M., Kataev, A. A., Grishchenko, V. M., Knyazeva, E. L., Permyakov, S. E., and Permyakov, E. A. (2009) Interaction of antitumor α-lactalbumin-oleic acid complexes with artificial and natural membranes. J. Bioenerg. Biomembr. 41, 229-237
51. Hsu, P. P., and Sabatini, D. M. (2008) Cancer cell metabolism. Warburg and beyond. Cell 134, 703-707
52. Menendez, J. A., and Lupu, R. (2007) Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat. Rev. Cancer 7, 763-777 (Pubitemid 47469806)
53. Nomura, D. K., Long, J. Z., Niessen, S., Hoover, H. S., Ng, S. W., and Cravatt, B. F. (2010) Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis. Cell 140, 49-61
54. Mashek, D. G., and Coleman, R. A. (2006) Cellular fatty acid uptake. The contribution of metabolism. Curr. Opin. Lipidol. 17, 274-278 (Pubitemid 43786061)
55. Le, A., Lane, A. N., Hamaker, M., Bose, S., Gouw, A., Barbi, J., Tsukamoto, T., Rojas, C. J., Slusher, B. S., Zhang, H., Zimmerman, L. J., Liebler, D. C., Slebos, R. J., Lorkiewicz, P. K., Higashi, R. M., Fan, T. W., and Dang, C. V. (2012) Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. Cell Metab. 15, 110-121
56. Zhang, W. C., Shyh-Chang, N., Yang, H., Rai, A., Umashankar, S., Ma, S., Soh, B. S., Sun, L. L., Tai, B. C., Nga, M. E., Bhakoo, K. K., Jayapal, S. R., Nichane, M., Yu, Q., Ahmed, D. A., Tan, C., Sing, W. P., Tam, J., Thirugananam, A., Noghabi, M. S., Pang, Y. H., Ang, H. S., Mitchell, W., Robson, P., Kaldis, P., Soo, R. A., Swarup, S., Lim, E. H., and Lim, B. (2012) Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell 148, 259-272
57. Svensson, M., Fast, J., Mossberg, A.-K., Düringer, C., Gustafsson, L., Hallgren, O., Brooks, C. L., Berliner, L., Linse, S., and Svanborg, C. (2003) α-Lactalbumin unfolding is not sufficient to cause apoptosis, but is required for the conversion to HAMLET (human α-lactalbumin made lethal to tumor cells). Protein Sci. 12, 2794-2804 (Pubitemid 37445103)
58. Pettersson-Kastberg, J., Mossberg, A. K., Trulsson, M., Yong, Y. J., Min, S., Lim, Y., O'Brien, J. E., Svanborg, C., and Mok, K. H. (2009) α-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