Joint forces of mass spectrometric techniques (ICP-MS and MALDI-TOF-MS) and fluorescence spectrometry in the study of platinum-based cytostatic drugs interactions with metallothionein MT2 and MT3

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Authors

PAVELICOVA Kristyna DO Tomas VEJVODOVÁ Markéta VACULOVIČ Tomáš NOWAK Kinga MATCZUK Magdalena WU Sylwia KREZEL Artur ADAM Vojtech VACULOVICOVA Marketa

Year of publication 2024
Type Article in Periodical
Magazine / Source Talanta
MU Faculty or unit

Faculty of Science

Citation
web https://www.sciencedirect.com/science/article/pii/S0039914024002996?via%3Dihub
Doi http://dx.doi.org/10.1016/j.talanta.2024.125920
Keywords Metal ions; Dimers; Laser ablation; Inductively coupled plasma; Mass spectrometry
Description Herby, the interaction of metallothioneins with commonly used Pt-based anticancer drugs - cisplatin, carboplatin, and oxaliplatin - was investigated using the combined power of elemental (i.e. LA-ICP-MS, CE-ICP-MS) and molecular (i.e. MALDI-TOF-MS) analytical techniques providing not only required information about the interaction, but also the benefit of low sample consumption. The amount of Cd and Pt incorporated within the protein was determined for protein monomers and dimer/oligomers formed by non-oxidative dimerization. Moreover, fluorescence spectrometry using Zn2+-selective fluorescent indicator - FluoZin3 - was employed to monitor the ability of Pt drugs to release natively occurring Zn from the protein molecule. The investigation was carried out using two protein isoforms (i.e. MT2, MT3), and significant differences in behaviour of these two isoforms were observed. The main attention was paid to elucidating whether the protein dimerization/oligomerization may be the reason for the potential failure of the anticancer therapy based on these drugs. Based on the results, it was demonstrated that the interaction of MT2 (both monomers and dimers) interacted with Pt drugs significantly less compared to MT3 (both monomers and dimers). Also, a significant difference between monomeric and dimeric forms (both MT2 and MT3) was not observed. This may suggest that dimer formation is not the key factor leading to the inactivation of Pt drugs.
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