Peroxisome proliferator-activated receptor gamma ligands induce growth inhibition and apoptosis of human B lymphocytic leukemia.
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.
Zang
Chuanbing
C
Division of Oncology/Hematology, School of Medicine (Charité), Humboldt University, Schumannstr. 20/21, 10117 Berlin, Germany.
Liu
Hongyu
H
Posch
Maximilian G
MG
Waechter
Maries
M
Facklam
Margit
M
Fenner
Martin H
MH
Ruthardt
Martin
M
Possinger
Kurt
K
Phillip Koeffler
H
H
Elstner
Elena
E
D000293:Adolescent; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002051:Burkitt Lymphoma / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008024:Ligands; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D018807:Polymorphism, Single-Stranded Conformational; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology*; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism*
C477819:15-deoxyprostaglandin J2; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D015230:Prostaglandin D2; D000077205:Pioglitazone