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Enhanced Antitumor Activity by the Combination of Dasatinib and Selinexor in Chronic Myeloid Leukemia.
- Source :
-
Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2024 Jul 05; Vol. 17 (7). Date of Electronic Publication: 2024 Jul 05. - Publication Year :
- 2024
-
Abstract
- Background: Chronic myeloid leukemia is a hematological malignancy characterized by the abnormal proliferation of leukemic cells. Despite significant progress with tyrosine kinase inhibitors, such as Dasatinib, resistance remains a challenge. The aim of the present study was to investigate the potential of Selinexor, an Exportin-1 inhibitor, to improve TKI effectiveness on CML.<br />Methods: Human CML cell lines (LAMA84 and K562) were treated with Selinexor, Dasatinib, or their combination. Apoptosis, mitochondrial membrane potential, and mitochondrial mass were assessed using flow cytometry. Real-time RT-PCR was used to evaluate the expression of genes related to mitochondrial function. Western blot and confocal microscopy examined PINK and heme oxygenase-1 (HO-1) protein levels.<br />Results: Selinexor induced apoptosis and mitochondrial depolarization in CML cell lines, reducing cell viability. The Dasatinib/Selinexor combination further enhanced cytotoxicity, modified mitochondrial fitness, and downregulated HO-1 nuclear translocation, which has been associated with drug resistance in different models.<br />Conclusions: In conclusion, this study suggests that Dasatinib/Selinexor could be a promising therapeutic strategy for CML, providing new insights for new targeted therapies.
Details
- Language :
- English
- ISSN :
- 1424-8247
- Volume :
- 17
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Pharmaceuticals (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 39065744
- Full Text :
- https://doi.org/10.3390/ph17070894