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Metallothionein and its relation to anticancer treatment by platinum complexes

Publication at Second Faculty of Medicine |
2008

Abstract

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 ušed.

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 ušed. 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.