نوع مقاله : مقاله مروری
نویسندگان
1 دانشیار بیوشیمی بالینی، دانشکده پزشکی، دانشگاه علوم پزشکی شیراز، شیراز، ایران
2 دانشجوی دکترا بیوشیمی بالینی، دانشکده پزشکی، دانشگاه علوم پزشکی شیراز، شیراز، ایران
3 دانشجوی فوق لیسانس بیوشیمی بالینی، دانشکده پزشکی، دانشگاه علوم پزشکی شیراز، شیراز، ایران
چکیده
پروتئین شیر، آلفا لاکتالبومین، یکی از پروتئینهایی است که مطالعات زیادی روی ساختار و عملکرد آن انجامشده است. در اواخر دهه 1990 فعالیت کاملاً متفاوتی از آن کشف شد. وقتی که آلفا لاکتالبومین درکانفورماسیونی قرار دارد که بهطور نسبی تانخورده است میتواند با اولئیک اسید تشکیل مجموعهای را دهد که بهطور اختصاصی فعالیت ضد سرطانی دارد. مجموعه حاصل از آلفا لاکتالبومین انسانی و اسید اولئیک، HAMLET نامیده میشود. مکانیسم مرگ سلولی توسط HAMLET هنوز بهطور دقیق مشخص نشده است، ولی نشان دادهشده است که HAMLET با اندامکهای مختلف سلولی ازجمله هسته، لیزوزم ها، میتوکندری، پروتئازوم ها وریبوزوم ها برهمکنش دارد. آپوپتوز، اتوفاژی و اختلال در ساختار کروماتین سه مسیر مختلف مسمومکنندهی سلولی هستند که در پاسخ به HAMLET فعال میشوند. در این مطالعه خلاصه ای از ساختار، مکانیسمهای ضد سرطانی و کاربردهای بالینی این مجموعه ارائه میشود.
کلیدواژهها
- HÅKANssoN A, Zhivotovsky B, Orrenius S, Sabharwal H, Svanborg C. Apoptosis induced by a human milk protein. Proceedings of the National Academy of Sciences. 1995; 92(17):8064-8.
- Svensson M, Sabharwal H, Hهkansson A, Mossberg A-K, Lipniunas P, Leffler H, et al. Molecular characterization of α–lactalbumin folding variants that induce apoptosis in tumor cells. Journal of Biological Chemistry. 1999; 274(10): 6388-96.
- Svanborg C, إgerstam H, Aronson A, Bjerkvig R, Düringer C, Fischer W, et al. HAMLET kills tumor cells by an apoptosis-like mechanism—cellular, molecular, and therapeutic aspects. Advances in cancer research. 2003; 88: 1-29.
- Gustafsson L, Hallgren O, Mossberg A-K, Pettersson J, Fischer W, Aronsson A, et al. HAMLET kills tumor cells by apoptosis: structure, cellular mechanisms, and therapy. The Journal of nutrition. 2005; 135(5): 1299-303.
- Svensson M, Hهkansson A, Mossberg A-K, Linse S, Svanborg C. Conversion of α-lactalbumin to a protein inducing apoptosis. Proceedings of the National Academy of Sciences. 2000; 97(8): 4221-6.
- Svensson M, Mossberg AK, Pettersson J, Linse S, Svanborg C. Lipids as cofactors in protein folding: Stereo‐specific lipid–protein interactions are required to form HAMLET (h uman α‐lactalbumin m ade le thal to t umor cells). Protein Science. 2003; 12(12):2805-14.
- Hill RL, Brew K. Lactose synthetase. Adv Enzymol Relat Areas Mol Biol. 1975; 43: 411-90.
- Pettersson J, Mossberg A-K, Svanborg C. α-Lactalbumin species variation, HAMLET formation, and tumor cell death. Biochemical and biophysical research communications. 2006;345(1):260-70.
- Iyer LK, Qasba PK. Molecular dynamics simulation of α-lactalbumin and calcium binding c-type lysozyme. Protein engineering. 1999; 12(2): 129-39.
- Permyakov EA, Berliner LJ. α‐Lactalbumin: structure and function. FEBS letters. 2000; 473(3): 269-74.
- Svensson M, HAKANSSON A, Mossberg A, LINSE C, Svanborg C. Conversion of-lactoglobulin to a protein inducing apoptosis. Proc Nat Acad Sci USA. 2000; 97: 42214226.
- Mossberg AK, Mok KH, Morozova‐Roche LA, Svanborg C. Structure and function of human α‐lactalbumin made lethal to tumor cells (HAMLET)‐type complexes. The FEBS journal. 2010; 277(22): 4614-25.
- Lin Y, Sun X, Hou X, Qu B, Gao X, Li Q. Effects of glucose on lactose synthesis in mammary epithelial cells from dairy cow. BMC veterinary research. 2016 Dec; 12 (1):81.
- Pettersson-Kastberg J, Mossberg A-K, Trulsson M, Yong YJ, Min S, Lim Y, et al. 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. Journal of molecular biology. 2009; 394(5): 994-1010.
- Kuwajima K. The molten globule state of alpha-lactalbumin. The FASEB Journal. 1996; 10(1): 102-9.
- Svensson M, Fast J, Mossberg AK, Düringer C, Gustafsson L, Hallgren O, et al. α‐Lactalbumin unfolding is not sufficient to cause apoptosis, but is required for the conversion to HAMLET (h uman α‐lactalbumin m ade le thal to t umor cells). Protein Science. 2003; 12(12): 2794-804.
- Fast J, Mossberg AK, Svanborg C, Linse S. Stability of HAMLET—A kinetically trapped α‐lactalbumin oleic acid complex. Protein Science. 2005; 14(2): 329-40.
- Mok KH, Pettersson J, Orrenius S, Svanborg C. HAMLET, protein folding, and tumor cell death. Biochemical and biophysical research communications. 2007; 354(1): 1-7.
- Casbarra A, Birolo L, Infusini G, Dal Piaz F, Svensson M, Pucci P, et al. Conformational analysis of HAMLET, the folding variant of human α‐lactalbumin associated with apoptosis. Protein science. 2004; 13(5): 1322-30.
- Tolin S, De Franceschi G, Spolaore B, Frare E, Canton M, de Laureto PP, et al. The oleic acid complexes of proteolytic fragments of α‐lactalbumin display apoptotic activity. The FEBS journal. 2010; 277(1): 163-73.
- Brinkmann C, Thiel S, Larsen M, Petersen T, Jensenius JC, Heegaard C. Preparation and comparison of cytotoxic complexes formed between oleic acid and either bovine or human α-lactalbumin. Journal of dairy science. 2011;94(5):2159-70.
- Knyazeva EL, Grishchenko VM, Fadeev RS, Akatov VS, Permyakov SE, Permyakov EA. Who is Mr. HAMLET? Interaction of human α-lactalbumin with monomeric oleic acid. Biochemistry. 2008;47(49):13127-37.
- Kamijima T, Ohmura A, Sato T, Akimoto K, Itabashi M, Mizuguchi M, et al. Heat-treatment method for producing fatty acid-bound alpha-lactalbumin that induces tumor cell death. Biochemical and biophysical research communications. 2008; 376(1): 211-4.
- Hkansson A, Andréasson J, Zhivotovsky B, Karpman D, Orrenius S, Svanborg C. Multimeric α-lactalbumin from human milk induces apoptosis through a direct effect on cell nuclei. Experimental cell research. 1999; 246(2): 451-60.
- Düringer C, Hamiche A, Gustafsson L, Kimura H, Svanborg C. HAMLET interacts with histones and chromatin in tumor cell nuclei. Journal of Biological Chemistry. 2003; 278(43): 42131-5.
- Hallgren O, Aits S, Brest P, Gustafsson L, Mossberg A-K, Wullt B, et al. Apoptosis and tumor cell death in response to HAMLET (human α-lactalbumin made lethal to tumor cells). Bioactive Components of Milk: Springer; 2008. p. 217-40.
- Gustafsson L, Aits S, ضnnerfjord P, Trulsson M, Storm P, Svanborg C. Changes in proteasome structure and function caused by HAMLET in tumor cells. PLoS One. 2009; 4(4): e5229.
- Brest P, Gustafsson M, Mossberg A-K, Gustafsson L, Duringer C, Hamiche A, et al. Histone deacetylase inhibitors promote the tumoricidal effect of HAMLET. Cancer research. 2007; 67(23): 11327-34.
- Kِhler C, Gogvadze V, Hهkansson A, Svanborg C, Orrenius S, Zhivotovsky B. A folding variant of human α‐lactalbumin induces mitochondrial permeability transition in isolated mitochondria. European journal of biochemistry. 2001; 268(1): 186-91.
- Kِhler C, Hهkansson A, Svanborg C, Orrenius S, Zhivotovsky B. Protease activation in apoptosis induced by MAL. Experimental cell research. 1999; 249(2): 260-8.
- Hallgren O, Gustafsson L, Irjala H, Selivanova G, Orrenius S, Svanborg C. HAMLET triggers apoptosis but tumor cell death is independent of caspases, Bcl-2 and p53. Apoptosis. 2006; 11(2): 221-33.
- Yorimitsu T, Klionsky DJ. Autophagy: molecular machinery for self-eating. Cell death and differentiation. 2005; 12(S2): 1542.
- Gozuacik D, Kimchi A. Autophagy and cell death. Current topics in developmental biology. 2007; 78: 217-45.
- Fischer W, Gustafsson L, Mossberg A-K, Gronli J, Mork S, Bjerkvig R, et al. 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 research. 2004; 64(6): 2105-12.
- Mossberg AK, Wullt B, Gustafsson L, Mهnsson W, Ljunggren E, Svanborg C. Bladder cancers respond to intravesical instillation of (HAMLET human α‐lactalbumin made lethal to tumor cells). International journal of cancer. 2007; 121(6): 1352-9.
- 36. Mossberg A-K, Hou Y, Svensson M, Holmqvist B, Svanborg C. HAMLET treatment delays bladder cancer development. The Journal of urology. 2010; 183(4): 1590-7.
- Gustafsson L, Leijonhufvud I, Aronsson A, Mossberg A-K, Svanborg C. Treatment of skin papillomas with topical α-lactalbumin–oleic acid. New England Journal of Medicine. 2004; 350(26): 2663-72.
- Gibbs S, Altman DG, Harvey I, Sterling J, Stark R. PapersLocal treatments for cutaneous warts: systematic reviewCommentary: Systematic reviewers face challenges from varied study designs. Bmj. 2002; 325(7362): 461.
- Gundersen S, Lote K, Hannisdal E. Prognostic factors for glioblastoma multiforme: development of a prognostic index. Acta Oncologica. 1996; 35(sup8): 123-7.
- 40. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta neuropathologica. 2007; 114(2): 97-109.
- Wen PY, Schiff D, Kesari S, Drappatz J, Gigas DC, Doherty L. Medical management of patients with brain tumors. Journal of neuro-oncology. 2006; 80(3): 313-32.
- Engebraaten O, Hjortland GO, Hirschberg H, Fodstad X. Growth of precultured human glioma biopsy specimens in nude rat brain. Journal of neurosurgery. 1999; 90(1): 125-32.
- Sengupta N, Siddiqui E, Mumtaz FH. Cancers of the bladder. The journal of the Royal Society for the Promotion of Health. 2004; 124(5): 228-9.
- Schenkman E, Lamm DL. Superficial bladder cancer therapy. The Scientific World Journal. 2004; 4: 387-99.