Evaluation of the accumulation of disulfiram and its copper complex in A549 cells using mass spectrometry.
Talanta
; 211: 120732, 2020 May 01.
Article
em En
| MEDLINE
| ID: mdl-32070566
ABSTRACT
The famous alcohol-aversion drug disulfiram (DSF) is a promising candidate for repurposing in cancer therapy, as indicated by many ongoing and completed clinical trials. Existing researches focus on demonstrating that the anti-cancer activity of DSF is enhanced by copper ions, or solving the problem that DSF is easily decomposed in the body to lose its activity. However, the metabolic kinetics of its ultimate anti-cancer metabolite DDC-Cu (bis-diethyldithiocarbamate-copper) in cells and how it exerts anti-cancer mechanisms remain unclear. In this work, mass spectrometric evaluation of the intracellular and extracellular accumulation of DSF and its copper complex DDC-Cu was performed. Combined with cytotoxicity assay, staining analysis and flow cytometry, we found that DDC-Cu could easily pass through the cell membrane of A549 cells, and accumulate intracellularly for a long time. This process can lead to cellular morphological changes, an increase in ROS content, cell cycle arrest in the G0/G1 phase and apoptosis. Besides, molecular cancer-relevant targets of DDC-Cu in cancer cells were further discussed. This work investigated the cytotoxic mechanism of DDC-Cu, which has important clinical significance for its application in cancer therapy.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Compostos Organometálicos
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Espectrometria de Massas
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Ditiocarb
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Cobre
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Dissulfiram
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Neoplasias Pulmonares
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Antineoplásicos
Tipo de estudo:
Evaluation_studies
Limite:
Humans
Idioma:
En
Revista:
Talanta
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China