An Adsorptive Transfer Technique Coupled with Brdicka Reaction to Reveal the Importance of Metallothionein in Chemotherapy with Platinum Based Cytostatics

Sona Krizkova,Pavel Pochop,Pavel Pochop,Jiri Kukacka,Vojtech Adam,Dalibor Huska,Tomas Eckschlager,Jan Hrabeta,Rene Kizek,Libuse Trnkova,Richard Prusa,Petr Babula,Ivo Fabrik,Denisa Darsova,Denisa Darsova

doi:10.3390/ijms11124826

Abstract

The drugs based on platinum metals represent one of the oldest, but also one of the most effective groups of chemotherapeutic agents. Thanks to many clinical studies it is known that resistance of tumor cells to drugs is a frequent cause of chemotherapy failure. With regard to platinum based drugs, multidrug resistance can also be connected with increased expression of low-molecular weight protein metallothionein (MT). This study aimed at investigating the interactions of MT with cisplatin or carboplatin, using the adsorptive transfer technique coupled with differential pulse voltammetry Brdicka reaction (AdTS DPV Brdicka reaction), and a comparison of in vitro results with results obtained in vivo. The results obtained from the in vitro study show a strong affinity between platinum based drugs and MT. Further, we analyzed extracts of neuroblastoma cell lines treated with cisplatin or carboplatin. It is clear that neuroblastoma UKF-NB-4 cisplatin-resistant and cisplatin-sensitive cell lines unlikely respond to the presence of the platinum-based cytostatics cisplatin and carboplatin. Finally, we determined the level of MT in samples from rabbits treated with carboplatin and patients with retinoblastoma treated with the same drug.

Highlights

From a contemporary point of view, the process of the origin of malignant tumors is complex and multifactorial, comprising changes in expression of individual genes, physical factors and exposure to different chemical and biological impulses
It is known that thiol compounds play a very important role in the processes linked to the formation of tumor cell resistance to platinum-based cytostatics [35,54,55]
In the first in vitro experiment, we targeted the monitoring of cisplatin and carboplatin interactions with MT

Summary

Introduction

From a contemporary point of view, the process of the origin of malignant tumors is complex and multifactorial, comprising changes in expression of individual genes, physical factors and exposure to different chemical and biological impulses. Individual tumor treatment strategies result from a number of treatment protocols combining an economic point of view and maximum benefit for the patient. Drugs based on platinum metals represent one of the oldest, and one of the most effective groups of chemotherapeutic agents [11,12,13,14,15,16,17,18,19,20,21]. Platinum-complex based chemotherapeutics are presently used in the therapy of a broad-spectrum of malignancies. The therapeutic effect of platinum-based therapeutics is permanently irreplaceable and brings considerable benefits to patients [23,24,25,26,27,28,29,30]

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Conclusion