title: BMS-777607 promotes megakaryocytic differentiation and induces polyploidization in the CHRF-288-11 cells.
abstract: Introduction of a polyploidy inducer is a promising strategy to achieve a high level of polyploidization during megakaryocytic (MK) differentiation. Here, we report that a multi-kinase inhibitor, BMS-777607, is a potent polyploidy inducer for elevating high ploidy cell formation in the MK-differentiated CHRF-288-11 (CHRF) cells. Our result showed that BMS-777607 strongly inhibited cell division without affecting cell viability when detected at day 1 after treatment. As a consequence, the high ploidy (≥8N) cells were accumulated in culture for 8 days, with an increase from 16.2 to 75.2 % of the total cell population. The elevated polyploidization was accompanied by the increased expression level of MK marker, CD41 (platelet glycoprotein IIb/IIIa, GPIIb/IIIa), suggesting that BMS-777607 promoted both polyploidization and commitment of MK-differentiated CHRF cells. Platelet-like fragments (PFs) were released by mature CHRF cells. Based on a flow cytometry assay, it was found that the PFs produced from BMS-777607-treated cells tended to have larger size and higher expression of GPIIb/IIIa, a receptor for platelet adhesion. Taken together, these results suggested that BMS-777607 promoted MK differentiation of CHRF cells and increased the functional property of platelet-like fragments.
authors.affiliation: Division of Chemical Engineering, Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama-cho, Toyonaka, Osaka, 560-8531, Japan.
authors.forename: Retno Wahyu
authors.initials: RW
authors.lastname: Nurhayati
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ojima
authors.forename: Masahito
authors.initials: M
authors.lastname: Taya
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics*; D002478:Cells, Cultured; D006801:Humans; D020014:K562 Cells; D040201:Platelet Membrane Glycoprotein IIb; D011123:Polyploidy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D013268:Stimulation, Chemical
chemical_list: D000631:Aminopyridines; C550356:N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; D040201:Platelet Membrane Glycoprotein IIb; D047428:Protein Kinase Inhibitors; D011728:Pyridones