Bosutinib, dasatinib, imatinib, nilotinib, and ponatinib differentially affect the vascular molecular pathways and functionality of human endothelial cells
| Autor: | Oren Pasvolsky, Avi Leader, Galit Granot, Ayala Gover-Proaktor, Oshrat Raz, Saar Shapira, Pia Raanani, Metsada Pasmanik-Chor |
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| Rok vydání: | 2018 |
| Předmět: |
Cancer Research
Transcription Genetic Cell Survival Angiogenesis Cell Culture Techniques Dasatinib Neovascularization Physiologic Antineoplastic Agents 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Leukemia Myelogenous Chronic BCR-ABL Positive hemic and lymphatic diseases Nitriles Toxicity Tests Human Umbilical Vein Endothelial Cells medicine Humans RNA-Seq Protein Kinase Inhibitors Tube formation Aniline Compounds business.industry Ponatinib Imidazoles Imatinib Hematology Pyridazines Pyrimidines Oncology chemistry Nilotinib 030220 oncology & carcinogenesis Imatinib Mesylate Quinolines Cancer research Endothelium Vascular business Tyrosine kinase Bosutinib Signal Transduction 030215 immunology medicine.drug |
| Zdroj: | Leukemia & Lymphoma. 60:189-199 |
| ISSN: | 1029-2403 1042-8194 |
| DOI: | 10.1080/10428194.2018.1466294 |
| Popis: | The tyrosine kinase inhibitors (TKIs), nilotinib, ponatinib, and dasatinib (but not bosutinib or imatinib), are associated with vascular adverse events (VAEs) in chronic myeloid leukemia (CML). Though the mechanism is inadequately understood, an effect on vascular cells has been suggested. We investigated the effect of imatinib, nilotinib, dasatinib, bosutinib, and ponatinib on tube formation, cell viability, and gene expression of human vascular endothelial cells (HUVECs). We found a distinct genetic profile in HUVECs treated with dasatinib, ponatinib, and nilotinib compared to bosutinib and imatinib, who resembled untreated samples. However, unique gene expression and molecular pathway alterations were detected between dasatinib, ponatinib, and nilotinib. Angiogenesis/blood vessel-related pathways and HUVEC function (tube formation/viability) were adversely affected by dasatinib, ponatinib, and nilotinib but not by imatinib or bosutinib. These results correspond to the differences in VAE profiles of these TKIs, support a direct effect on vascular cells, and provide direction for future research. |
| Databáze: | OpenAIRE |
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