Thiazolidinedione suppresses the expression of erythroid phenotype in erythroleukemia cell line K562.
The activation of PPARgamma:RXR nuclear system induces monocytic differentiation of some myelogeneous leukemia cell lines. The present study was undertaken to examine the effect of PPARgamma ligand, TZD (troglitazone or pioglitazone) and/or RXR selective ligand, LG100268 on the erythroleukaemia cell line K562 which has both an erythroid character and a potential for differentiation into megakaryocytes. TZD suppressed cell proliferation and the erythroid phenotype of K562 cells. The suppression of erythroid phenotype of K562 cells by TZD was synergistically enhanced by the combined treatment with LG100268. Moreover, the marked suppression of erythroid phenotype in K562 cells was also accompanied by the downregulation of the erythroid lineage-transcription factor, GATA-1. These novel actions of troglitazone may provide a biochemical basis for anemia occasionally which is observed after the in vivo administration of TZD.
Hirase
N
N
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, Japan. nh6@alles.or.jp
Yanase
T
T
Mu
Y
Y
Muta
K
K
Umemura
T
T
Takayanagi
R
R
Nawata
H
H
D002454:Cell Differentiation / Q000187:drug effects; D004912:Erythrocytes / Q000473:pathology*; D006801:Humans; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008024:Ligands; D009687:Nuclear Proteins / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D047488:Retinoid X Receptors; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism
D008024:Ligands; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; C089946:2,4-thiazolidinedione