Sensitization of Multidrug Resistant Cancer Cells to Doxorubicin Using Ebselen by Disturbing Cellular Redox Status.
Humans
Organoselenium Compounds
/ pharmacology
Isoindoles
/ pharmacology
Doxorubicin
/ pharmacology
Azoles
/ pharmacology
Drug Resistance, Neoplasm
/ drug effects
Oxidation-Reduction
Drug Resistance, Multiple
/ drug effects
Reactive Oxygen Species
/ metabolism
Cell Survival
/ drug effects
Apoptosis
/ drug effects
Cell Proliferation
/ drug effects
Cell Line, Tumor
antioxidants
apoptosis
chemosensitization
multidrug resistance
redox status
Journal
Cell biochemistry and function
ISSN: 1099-0844
Titre abrégé: Cell Biochem Funct
Pays: England
ID NLM: 8305874
Informations de publication
Date de publication:
Sep 2024
Sep 2024
Historique:
revised:
20
09
2024
received:
23
06
2024
accepted:
25
09
2024
medline:
9
10
2024
pubmed:
9
10
2024
entrez:
9
10
2024
Statut:
ppublish
Résumé
Multidrug resistance (MDR) poses a significant problem in cancer treatment, often causing adverse effects during chemotherapy. Ebselen (Ebs), a synthetic organoselenium compound, affects cellular redox status in cancer cells. In the study, we observed that Ebs disrupted cellular redox balance and sensitized drug-resistant cells to doxorubicin (DOX) treatment. The combination of Ebs and DOX led to increased intracellular reactive oxygen species (ROS) levels and lipid peroxidation while decreasing the activity of thioredoxin reductase (TrxR) and cellular antioxidants in drug-resistant cells. Furthermore, this combination treatment demonstrated notable chemosensitizing effects by reducing cell viability and proliferation in MDR cells compared to DOX treatment alone. Additionally, the combination of Ebs and DOX induced DNA fragmentation and exhibited G2/M phase cell cycle arrest. Immunofluorescent analysis revealed that the Ebs and DOX combination upregulated the expression of p53 and p21, which activated the mitochondrial-dependent apoptotic pathway. The combination treatment also enhanced the upregulation of proapoptotic markers such as Bax, Caspase-3, -9, and cytochrome C, while downregulating the expression of the antiapoptotic marker Bcl-2. Therefore, the current discoveries suggest that Ebs could be employed as a drug candidate for reversing MDR in cancer cells by regulating cellular redox homeostasis.
Substances chimiques
Organoselenium Compounds
0
Isoindoles
0
Doxorubicin
80168379AG
ebselen
40X2P7DPGH
Azoles
0
Reactive Oxygen Species
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e4134Informations de copyright
© 2024 John Wiley & Sons Ltd.
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