Peroxisome proliferator-activated receptor γ ligands induce growth inhibition and apoptosis of human B lymphocytic leukemia

被引：39

作者：

Zang, CB

Liu, HY

Posch, MG

Waechter, M

Facklam, M

Fenner, MH

Ruthardt, M

Possinger, K

Koeffler, HP

Elstner, E

机构：

[1] Humboldt Univ, Sch Med, Div Hematol Oncol, Charite, D-10117 Berlin, Germany

[2] Goethe Univ Frankfurt, Sch Med, Lab Expt Hematol, Mainz, Germany

[3] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Div Hematol Oncol, Los Angeles, CA 90048 USA

来源：

LEUKEMIA RESEARCH | 2004年 / 28卷 / 04期

基金：

美国国家卫生研究院;

关键词：

acute lymphocytic leukemia; peroxisome proliferator-activated receptor gamma; pioglitazone; proliferation; apoptosis;

D O I：

10.1016/j.leukres.2003.07.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

This study examined the expression and structural intactness of peroxisome proliferator-activated receptor gamma (PPARgamma) in human acute lymphocytic leukemia (ALL) cells and determined the effect of PPARgamma ligands on growth and apoptosis of these cells. We noted that all lymphocytic leukemia cell lines expressed PPARgamma and no PPARgamma mutations were found in these cell lines as indicated by SSCP analysis. Effect of the PPARgamma ligands on the proliferation, differentiation and apoptosis of B type ALL cells was further examined. Treatment of these cells with the PPARgamma ligands Pioglitazone (PGZ) and 15-deoxy-delta (12,14)-prostaglandin J2 (15d-PGJ2) resulted in growth inhibition in a dose-dependent manner which was associated with a G1 to S cell cycle arrest. However, this effect appeared to be PPARgamma-independent. since several PPARgamma antagonists could not reverse this effect. No differentiation was induced by this treatment. Four out of five cell lines underwent apoptosis after culture with the PPARgamma ligands. This effect was partially caspase-dependent because a pan-caspase inhibitor partially reversed this effect. In conclusion, our results suggest that PPARgamma ligands may offer a new therapeutic approach to aid in the treatment of ALL. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：387 / 397

页数：11

共 54 条

[1]

Asou H, 1999, INT J ONCOL, V15, P1027

[2] Thiazolidinediones produce a conformational change in peroxisomal proliferator-activated receptor-gamma: Binding and activation correlate with antidiabetic actions in db/db mice [J].