COMPARISON OF INTERACTION OF TWO ISOFORMS OF METALLOTHIONEIN (POTENTIAL SOURCE OF THE ANTITUMOR DRUG RESISTANCE) WITH PLATINUM-BASED CYTOSTATICS AND PLATINUM NANOPARTICLES

Platinum-based cytostatics are the metal-containing anticancer cytostatic drugs that have found application in clinical practice. Antitumor activity of platinum-based drugs is caused by the crosslinking of DNA and formation of DNA adducts with subsequent triggering the apoptosis leading to cell death. Disadvantage of this type of cytostatics is that some kind of cancer is resistant against them. This resistance can be potentially caused by metalloproteins such as metallothioneins (MTs) that bind platinum to their structure and make the interaction with DNA of cell impossible. MTs are low molecular mass, intracellular cysteine-rich, metal-binding proteins and ensure a number of functions in body for example detoxification of heavy metals or maintenance cellular zinc homeostasis. In this work, the interaction between two isoforms of MTs (MT3 and MT2) and several types of platinum cytostatics (oxaliplatin, carboplatin and cisplatin) as well as platinum nanoparticles (size of 10 and 40 nm) were examined by fluorimetric analysis using a fluorescence zinc indicator (Fluozin-3). Fluorescence spectrometry with laser-induced fluorescence detection (ex-488 nm, em-520 nm) was used in the study.