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Combination of ERK2 inhibitor VX-11e and voreloxin synergistically enhances anti-proliferative and pro-apoptotic effects in leukemia cells
- Source :
- Apoptosis
- Publication Year :
- 2019
-
Abstract
- ERK1/2 inhibitors are new promising anticancer drugs. The aim of this study was to investigate the effect of the combination of ERK2 inhibitor VX-11e and voreloxin on MOLM-14, K562, REH and MOLT-4 leukemia cell lines. We found that VX-11e alone and in combination with voreloxin significantly decreased ERK activation in all cell lines tested. To evaluate the interactions of the drugs, cells were treated for 24 h with VX-11e or voreloxin alone and in combination at fixed ratios based on IC50 values. The combinatorial effects of both drugs were synergistic over a wide range of concentrations in MOLM-14, REH and MOLT-4 cell lines. In K562 cells, three effects were found to be additive, one antagonistic and only one synergistic. The results showed that incubation with both VX-11e and voreloxin inhibited the growth of leukemia cells, affected cell cycle and induced apoptosis. Furthermore, the molecular mechanism of these effects might be attributed to an increased expression of p21 and a decreased expression of survivin and NF-κB in all cell lines tested except from K562 cells. In conclusion, combination of VX-11e and voreloxin can exert a synergistic anticancer effect in leukemia cells.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Cyclin-Dependent Kinase Inhibitor p21
Cancer Research
voreloxin
MAP Kinase Signaling System
Clinical Biochemistry
VX-11e
Pharmaceutical Science
Apoptosis
Cell cycle
Article
03 medical and health sciences
0302 clinical medicine
Survivin
Antineoplastic Combined Chemotherapy Protocols
medicine
Humans
leukemia cell lines
Naphthyridines
Voreloxin
Incubation
Cell Proliferation
Pharmacology
Mitogen-Activated Protein Kinase 1
Leukemia
Mitogen-Activated Protein Kinase 3
Dose-Response Relationship, Drug
Chemistry
Biochemistry (medical)
NF-kappa B
apoptosis
Drug Synergism
Cell Biology
Cell Cycle Checkpoints
medicine.disease
Leukemia cell lines
Thiazoles
030104 developmental biology
Cell culture
030220 oncology & carcinogenesis
Cancer research
cell cycle
K562 Cells
K562 cells
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Apoptosis
- Accession number :
- edsair.doi.dedup.....73b1e03d2c42c4d1c9d1979207f4ad02