Interaction of platinum-based cytostatics and platinum nanoparticles with metallothionein - potencial source of the antitumor drug resistence

Abstract

Platinum-based cytostatic represent a unique class of DNA-damaging antitumor agents and they are one the most frequently used drugs in oncology. Problem is that some kind of cancer is resistant against this type of cytostatics. This resistance can be potentially caused by metalloproteins such as metallothioneins. MTs belong to the group of intracellular cystine-rich, metal-binding proteins and hold a number of functions in body. One of them is detoxification of heavy metals. This ability of MTs can cause a decreased therapeutic effect of platinum-based cytostatics. In this work, the interaction between two isoforms of MTs (MT3 and MT2a) and several types of platinum cytostatics (oxaliplatin, carboplatin and cisplatin) as well as platinum nanoparticles (size of 10 and 40 nm) was examined by fluorimetric analysis using a fluorescence zinc indicator (Fluozin-3). Both, stationary fluorescence spectrometry and capillary electrophoresis with laser-induced fluorescence detection (ex - 488 nm, em - 530 nm) was used in the study.Platinum-based cytostatic represent a unique class of DNA-damaging antitumor agents and they are one the most frequently used drugs in oncology. Problem is that some kind of cancer is resistant against this type of cytostatics. This resistance can be potentially caused by metalloproteins such as metallothioneins. MTs belong to the group of intracellular cystine-rich, metal-binding proteins and hold a number of functions in body. One of them is detoxification of heavy metals. This ability of MTs can cause a decreased therapeutic effect of platinum-based cytostatics. In this work, the interaction between two isoforms of MTs (MT3 and MT2a) and several types of platinum cytostatics (oxaliplatin, carboplatin and cisplatin) as well as platinum nanoparticles (size of 10 and 40 nm) was examined by fluorimetric analysis using a fluorescence zinc indicator (Fluozin-3). Both, stationary fluorescence spectrometry and capillary electrophoresis with laser-induced fluorescence detection (ex - 488 nm, em - 530 nm) was used in the study.