Sodium diethyldithiocarbamate trihydrate: an effective and selective compound for hematological malignancies.
Apoptosis
Leukemia
Lymphoma
Selectivity
Sodium diethyldithiocarbamate
Journal
Naunyn-Schmiedeberg's archives of pharmacology
ISSN: 1432-1912
Titre abrégé: Naunyn Schmiedebergs Arch Pharmacol
Pays: Germany
ID NLM: 0326264
Informations de publication
Date de publication:
26 Aug 2024
26 Aug 2024
Historique:
received:
04
07
2024
accepted:
18
08
2024
medline:
26
8
2024
pubmed:
26
8
2024
entrez:
26
8
2024
Statut:
aheadofprint
Résumé
Myeloid leukemias and lymphomas are among the most common and well-studied hematological malignancies. However, due to the aggressiveness and rapid progression of certain subtypes, treating these diseases remains a challenge. Considering the promising results of diethyldithiocarbamates in preclinical and clinical oncology trials, this study aimed to investigate the potential of sodium diethyldithiocarbamate trihydrate (DETC) as a prototype for developing new drugs to treat hematological malignancies. In silico analysis using SwissADME was conducted to evaluate the physicochemical characteristics and pharmacokinetic properties of DETC. An in vitro investigation utilizing the MTT assay assessed the cytotoxic effects of DETC on neoplastic and non-neoplastic cell lines. Selectivity was determined using a selectivity index and a hemolysis assay, while the mechanism of cell death in neoplastic cell lines was examined through flow cytometry analysis of pro-apoptotic and anti-apoptotic protein levels. The results demonstrated that the physicochemical characteristics of DETC are suitable for oral administration. Furthermore, the compound showed promising cytotoxic activity against human myeloid leukemia (K562) and Burkitt's lymphoma (Daudi) cell lines, with high selectivity for neoplastic cells over non-neoplastic cells of the bone marrow microenvironment (HS-5 cell line). Moreover, hemolysis was observed only at very high concentrations. The cytotoxicity mechanism of DETC against both neoplastic cell lines involved cell cycle arrest and the production of reactive oxygen species. In K562 cells, cell death was induced via apoptosis. Additional experiments are needed to confirm the exact mechanism of cell death in Daudi Burkitt's lymphoma cells.
Identifiants
pubmed: 39186189
doi: 10.1007/s00210-024-03399-8
pii: 10.1007/s00210-024-03399-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
ID : There is no Grant ID
Organisme : Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
ID : There is no Grant ID
Organisme : Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
ID : There is no Grant ID
Organisme : Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
ID : There is no Grant ID
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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