[EPO mediated proliferation and differentiation of human erythroid progenitor inhibited by FK228].
OBJECTIVE
To investigate the function of histone deacetylases (HDACs) inhibitor FK228 in the EPO mediated proliferation and differentiation of human erythroid progenitor.


METHODS
CD34(+) cells were separated from the granulocyte colony-stimulating factor-mobilized peripheral blood of patients with cancer. They were cultured for 7 days with serum-free medium containing stem cell factor (SCF), erythropoietin (EPO) or SCF+IL-3 in the presence of escalated dosages of FK228. After immunofluorescent staining with anti-GPA-PE and anti-CD36-FITC, cell count and Flow cytometric analysis were performed; CD34(+) cells were cultured for 7 days with serum-free medium containing SCF+IL-3 and enriched for CD36(+) GPA(-) cells, which were cultured for 7 days with serum-free medium containing EPO+FK228. Then the cell count was conducted. CD36(+) GPA(-) cells were cultured for 7 days with serum-free medium containing EPO in the presence or absence of FK228 and then they were stained with annexin V and PI.


RESULTS
FK228 inhibited the generation of CD36(+) GPA(high), CD36(+) GPA(low) and CD36(+) GPA(-) cells in a dosage-dependent manner. FK228 induced the apoptosis of CD36(+) GPA(high) and CD36(+) GPA(low/-) cells in the presence of EPO.


CONCLUSIONS
FK228 can inhibit the EPO mediated proliferation and differentiation of human erythroid progenitor.
Yu
Zhao-cai
ZC
Department of Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. yzhaocai@fmmu.edu.cn
Liu
Wen-chao
WC
Fan
Li
L
Oishi
Koshi
K
Katayama
Naoyuki
N
D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D047630:Depsipeptides / Q000494:pharmacology*; D004921:Erythropoietin / Q000494:pharmacology*; D005434:Flow Cytometry; D006021:Glycophorins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D019089:Stem Cell Factor / Q000494:pharmacology
D018952:Antigens, CD34; D047630:Depsipeptides; C409972:GYPA protein, human; D006021:Glycophorins; D056572:Histone Deacetylase Inhibitors; D019089:Stem Cell Factor; D004921:Erythropoietin; C087123:romidepsin