Metallothionein and its relation to anticancer treatment by platinum complexes
Authors:
I. Fabrik 1; J. Kukačka 2; V. Adam 1; R. Průša 2; T. Eckschlager 3; R. Kizek 1
Authors‘ workplace:
Laboratoř molekulární biochemie a bioelektrochemie
Ústav chemie a biochemie, Mendelova zemědělská
a lesnická univerzita Brno
Děkan: prof. Ing. Ladislav Zeman, CSc.
1; Ústav klinické biochemie a patobiochemie II. LF UK, Praha
Přednosta: prof. MUDr. Richard Průša, CSc.
2; Klinika dětské hematologie a onkologie II. LF UK, Praha
Přednosta: prof. MUDr. Jan Starý, DrSc.
3
Published in:
Prakt. Lék. 2008; 88(2): 90-93
Category:
Various Specialization
Overview
Metallothionein:
It is a small protein with high content of cysteine, whose sulfhydryl groups give metallothionein its unique properties. In organism metallothionein transports metal ions (Zn, Cu), but it can even bind and eliminate toxic metal ions (Cd, Pb, Hg, etc.). Metallothionein helps to cells handle oxidative stress and it regulates level of expression and enzymatic activity.
Cytostatics based on platinum:
This type of cytostatics belongs to the oldest and most used. They are based on platinum complexes with changing ligands. The oldest member of this group, cisplatine, has more effective analogues (platinum complexes of second and third generation, carboplatin and oxaliplatin, and new are under development). Nevertheless cisplatin is still widely used. At some patients it developed phenomena of resistance of tumour cells, which of course lower effectiveness of treatment.
Induction of resistance and its mechanisms:
Resistance of tumour cell to cytostatics is complex process which involves many mechanisms. Some of them are relatively known to us; first of all it is regulation of intracellular concentration of drug and its efflux, complexation by intracellular thiols (glutathione and metallothionein) and mechanisms for repairing of damaged DNA.
Conclusion:
Research of this problems progresses very quickly and new information wait ahead us not only about influence of metallothionein on induction of resistance. It is one of preconditions for more effective treatment and understanding of metabolism of tumour disease.
Key words:
Metallothionein, cisplatin, resistance, tumour disease.
Sources
1. Margoshes, M., Vallee, B.L. A cadmium protein from equine kidney cortex. J. Am. Chem. Soc. 1957, 79, 17, p. 4813-4814.
2. Coyle, P., Philcox, J.C., Carey, L.C., Rofe, A.M. Metallothionein: The multipurpose protein. Cell Mol. Life. Sci. 2002, 59, 4, p. 627-647.
3. Miles, A.T., Hawksworth, G.M., Beattie, J.H., Rodilla, V. Induction, regulation, degradation, and biological significance of mammalian metallothioneins. Critical Reviews in Biochemistry and Molecular Biology 2000, 35, 1, p. 35-70.
4. Masters, B.A., Quaife, C.J., Erickson, J.C. et al. Metallothionein-Iii is expressed in neurons that sequester zinc in synaptic vesicles. J. Neurosci. 1994, 14, 10, p. 5844-5857.
5. Quaife, C.J., Findley, S.D., Erickson, J.C. et al. Induction of a new metallothionein isoform (Mt-Iv) occurs during differentiation of stratified squamous epithelia. Biochemistry 1994, 33, 23, p. 7250-7259.
6. Trayhurn, P., Duncan, J.S., Wood, A.M., Beattie, J.H. Metallothionein gene expression and secretion in white adipose tissue. Am. J. Physiol-Regul. Integr. Comp. Physiol. 2000, 279, 6, p. R2329-R2335.
7. Thirumoorthy, N., Kumar, K.T.M., Sundar, A.S., Panayappan, L., Chatterjee, M. Metallothionein: An overview. World Journal of Gastroenterology 2007, 13, 7, p. 993-996.
8. Murray, R.K., Granner, D.K., Mayes, P.A., Rodwell, V.W. Harper’s Illustrated Biochemistry. New York: Lange Medical Books/McGraw-Hill Medical Publishing Division, 2003.
9. Peng, B., English, M.W., Boddy, A.V. et al. Cisplatin pharmacokinetics in children with cancer. Eur. J. Cancer 1997, 33, 11, p. 1823-1828.
10. Maret, W., Vallee, B.L. Thiolate ligands in metallothionein confer redox activity on zinc clusters. Proc. Natl. Acad. Sci. USA 1998, 95, 7, p. 3478-3482.
11. Hanada, K., Sawamura, D., Tamai, K. et al. Novel function of metallothionein in photoprotection: Metallothionein-null mouse exhibits reduced tolerance against ultraviolet B injury in the skin. J. Invest. Dermatol. 1998, 111, 4, p. 582-585.
12. Hansen, C., Ablett, E., Green, A. et al. Biphasic response of the metallothionein promoter to ultraviolet radiation in human melanoma cells. Photochem. Photobiol. 1997, 65, 3, p. 550-555.
13. Bataineh, Z.M., Nusier, M.K. Metallothionein expression in human prostate gland. Saudi Med. J. 2003, 24, 11, p. 1246-1249.
14. Ejnik, J., Munoz, A., Gan, T., Shaw, C.F., Petering, D.H. Interprotein metal ion exchange between cadmium-carbonic anhydrase and apo- or zinc-metallothionein. J. Biol. Inorg. Chem. 1999, 4, 6, p. 784-790.
15. Cherian, M.G., Apostolova, M.D. Nuclear localization of metallothionein during cell proliferation and differentiation. Cell Mol. Biol. 2000, 46, 2, p. 347-356.
16. Zeng, J., Heuchel, R., Schaffner, W., Kagi, J.H.R. Thionein (apometallothionein) can modulate DNA-binding and transcription activation by zinc finger containing factor-Sp1. FEBS Lett. 1991, 279, 2, p. 310-312.
17. Klassen, R.B., Crenshaw, K., Kozyraki, R. et al. Megalin mediates renal uptake of heavy metal metallothionein complexes. Am. J. Physiol-Renal Physiol. 2004, 287, 3, p. F393-F403.
18. Ghoshal, K., Jacob, S.T. Regulation of metallothionein gene expression. Progress in Nucleic Acid Research and Molecular Biology Vol 66. San Diego: Academic Press Inc, 2001: p. 357-384.
19. Gunes, C., Heuchel, R., Georgiev, O. et al. Embryonic lethality and liver degeneration in mice lacking the metal-responsive transcriptional activator MTF-1. Embo. J. 1998, 17, 10, p. 2846-2854.
20. Santon, A., Irato, P., Medici, V., D‘Inca, R., Albergoni, V., Sturniolo, G.C. Effect and possible role of Zn treatment in LEC rats, an animial model of Wilson‘s disease. Biochem. Biophys. Acta-Mol, Basis Dis. 2003, 1637, 1, p. 91-97.
21. Waalkes, M.P., Liu, J., Goyer, R.A., Diwan, B.A. Metallothionein-I/II double knockout mice are hypersensitive to lead-induced kidney carcinogenesis: Role of inclusion body formation. Cancer Res. 2004, 64, 21, p. 7766-7772.
22. Jasani, B., Schmid, K.W. Significance of metallothionein overexpression in human. Histopathology 1997, 31, 3, p. 211-214.
23. Rosenber.B, Vancamp, L., Krigas, T. Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode. Nature 1965, 205, 4972, p. 698-707.
24. Perez, R.P. Cellular and molecular determinants of cisplatin resistance. Eur. J. Cancer 1998, 34, 10, p. 1535-1542.
25. Chu, G. Cellular-responses to cisplatin - the roles of DNA-binding proteins and DNA-repair. J. Biol. Chem. 1994, 269, 2, p. 787-790.
26. Searle, J., Kerr, J.F.R., Bishop, C.J. Necrosis and apoptosis - distinct modes of cell-death with fundamentally different significance. Pathol. Annu. 1982, 17, p. 229-259.
27. Searle, P.F., Stuart, G.W., Palmiter, R.D. Building a metal-responsive promoter with synthetic regulatory elements. Mol. Cell Biol. 1985, 5, 6, p. 1480-1489.
28. Safaei, R., Howell, S.B. Copper transporters regulate the cellular pharmacology and sensitivity to Pt drugs. Crit. Rev. Oncol/Hematol. 2005, 53, 1, p. 13-23.
29. Stordal, B., Davey, M. Understanding cisplatin resistance using cellular models. IUBMB Life 2007, 59, 11, p. 696-9.
30. Wlodek, L. Beneficial and harmful effects of thiols. Pol. J. Pharmacol. 2002, 54, 3, p. 215-23.
31. Meister, A., Anderson, M.E. Glutathione. Annu. Rev. Biochem. 1983, 52, p. 711-760.
32. Mistry, P., Kelland, L.R., Abel, G., Sidhar, S., Harrap, K.R. The relationships between glutathione, glutathione-S-transferase and cytotoxicity of platinum drugs and melphalan in 8 human ovarian-carcinoma cell-lines. Br. J. Cancer 1991, 64, 2, p. 215-220.
33. Soriani, M., Hejmadi, V., Tyrrell, R.M. Modulation of c-jun and c-fos transcription by UVB and UVA radiations in human dermal fibroblasts and KB cells. Photochem. Photobiol. 2000, 71, 5, p. 551-558.
34. Kagi, J.H.R. Overview of Metallothionein. Method. Enzymol. 1991, 205, p. 613-626.
35. Cherian, M.G., Howell, S.B., Imura, N. et al. Contemporary-Issues in toxicology - role of metallothionein in carcinogenesis. Toxicol. Appl. Pharmacol. 1994, 126, 1, p. 1-5.
Labels
General practitioner for children and adolescents General practitioner for adultsArticle was published in
General Practitioner
2008 Issue 2
Most read in this issue
- Memory and its disturbances
- Current possibilities and problems of antiretroviral therapy
- The hoarding of possessions and animals
- Acute toxic hepatitis following consumption of a herbal preparation