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.
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