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Study of Interactions between Metallothionein and Cisplatin by using Differential Pulse Voltammetry Brdickás reaction

Dalibor Huska1, Ivo Fabrik, Jiri Baloun

  • 1Department of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University of Agriculture and Forestry, Zemedelska 1, CZ-613 00 Brno, Czech Republic.

Sensors (Basel, Switzerland)
|May 11, 2012
PubMed

Insights

Metallothionein (MT) interacts with cisplatin, forming a complex that may cause anti-cancer drug resistance. This MT-cisplatin complex was detected rapidly and even in vivo, offering insights into platinum-cytostatic resistance mechanisms.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Analytical Chemistry

Background:

  • Personalized medicine for tumour diseases necessitates understanding drug resistance mechanisms.
  • Metallothionein (MT), a low molecular mass protein, is implicated in resistance to platinum-cytostatic drugs.
  • Early detection of resistance mechanisms is crucial for effective cancer treatment strategies.

Purpose of the Study:

  • To investigate the interaction between metallothionein (MT) and cisplatin.
  • To determine the kinetics of MT-cisplatin complex formation.
  • To confirm the presence of the MT-cisplatin complex in a biological system.

Main Methods:

  • Adsorptive transfer stripping technique.
  • Differential pulse voltammetry (DPV) using Brdickás reaction.
  • Quartz crystal microbalance (QCM) analyses.
  • Detection in blood samples from male rats.

Main Results:

  • A distinct MT-cisplatin complex signal was observed at -0.9 V using DPV.
  • Complex formation was time-dependent, detectable within 20 seconds of interaction.
  • QCM analysis confirmed the formation of the MT-cisplatin complex.
  • The MT-cisplatin complex was detected in the blood of rats treated with cisplatin.

Conclusions:

  • Metallothionein directly interacts with cisplatin, forming a detectable complex.
  • The rapid formation of this complex suggests a potential mechanism for acquired resistance to platinum-cytostatics.
  • In vivo detection of the MT-cisplatin complex in rat blood warrants further investigation into its role in clinical resistance.
Keywords:
Brdickás reactionCancerCisplatinMetallothioneinProtein-Drug InteractionQuartz Crystal MicrobalanceVoltammetry

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