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
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
38574532
DOI
10.1016/j.talanta.2024.125920
PII: S0039-9140(24)00299-6
Knihovny.cz E-resources
- Keywords
- Dimers, Inductively coupled plasma, Laser ablation, Mass spectrometry, Metal ions,
- MeSH
- Cisplatin pharmacology MeSH
- Cytostatic Agents pharmacology chemistry MeSH
- Spectrometry, Fluorescence * methods MeSH
- Mass Spectrometry methods MeSH
- Carboplatin pharmacology MeSH
- Humans MeSH
- Metallothionein 3 MeSH
- Metallothionein * metabolism chemistry MeSH
- Organoplatinum Compounds pharmacology chemistry MeSH
- Oxaliplatin pharmacology MeSH
- Platinum chemistry MeSH
- Antineoplastic Agents pharmacology chemistry MeSH
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization * methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Cisplatin MeSH
- Cytostatic Agents MeSH
- Carboplatin MeSH
- Metallothionein 3 MeSH
- Metallothionein * MeSH
- Organoplatinum Compounds MeSH
- Oxaliplatin MeSH
- Platinum MeSH
- Antineoplastic Agents MeSH
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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