Ponatinib reduces viability, migration, and functionality of human endothelial cells
| Autor: | Galit Granot, Saar Shapira, Ayala Gover-Proaktor, Pia Raanani, Aida Inbal, Oren Pasvolsky, Arnon Nagler, Ido Lubin, Oshrat Raz, Avi Leader, Dorit L. Lev |
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| Rok vydání: | 2016 |
| Předmět: |
Cancer Research
Cell Survival Gene Expression Antineoplastic Agents Apoptosis 030204 cardiovascular system & hematology Biology Endothelial progenitor cell Immunophenotyping Colony-Forming Units Assay 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Movement Leukemia Myelogenous Chronic BCR-ABL Positive Human Umbilical Vein Endothelial Cells medicine Humans Protein Kinase Inhibitors Tube formation Macrophages Ponatinib Imidazoles Endothelial Cells Myeloid leukemia Imatinib Hematology Vascular Endothelial Growth Factor Receptor-2 Pyridazines Endothelial stem cell Phenotype Oncology chemistry Nilotinib 030220 oncology & carcinogenesis Immunology cardiovascular system Cancer research Tyrosine kinase Biomarkers medicine.drug |
| Zdroj: | Leukemia & Lymphoma. 58:1455-1467 |
| ISSN: | 1029-2403 1042-8194 |
| DOI: | 10.1080/10428194.2016.1239258 |
| Popis: | Tyrosine kinase inhibitors (TKIs) have revolutionized the prognosis of chronic myeloid leukemia. With the advent of highly efficacious therapy, the focus has shifted toward managing TKI adverse effects, such as vascular adverse events (VAEs). We used an in vitro angiogenesis model to investigate the TKI-associated VAEs. Our data show that imatinib, nilotinib, and ponatinib reduce human umbilical vein endothelial cells (HUVECs) viability. Pharmacological concentrations of ponatinib induced apoptosis, reduced migration, inhibited tube formation of HUVECs, and had a negative effect on endothelial progenitor cell (EPC) function. Furthermore, in HUVECs transfected with VEGF receptor 2 (VEGFR2), the effect of ponatinib on tube formation and on all parameters representing normal endothelial cell function was less prominent than in control cells. This is the first report regarding the pathogenesis of ponatinib-associated VAEs. The antiangiogenic effect of ponatinib, possibly mediated by VEGFR2 inhibition, as shown in our study, is another piece in the intricate puzzle of TKI-associated VAEs. |
| Databáze: | OpenAIRE |
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