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

• Published in: Leukemia research Vol. 28; no. 4; pp. 387 - 397
• Main Authors: Zang, Chuanbing, Liu, Hongyu, Posch, Maximilian G, Waechter, Maries, Facklam, Margit, Fenner, Martin H, Ruthardt, Martin, Possinger, Kurt, Phillip Koeffler, H, Elstner, Elena
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2004
• Subjects: Acute lymphocytic leukemia; Adolescent; Apoptosis; Apoptosis - drug effects; Blotting, Western; Burkitt Lymphoma - metabolism; Burkitt Lymphoma - pathology; Cell Cycle - drug effects; Cell Division - drug effects; Cell Line, Tumor; Child; Child, Preschool; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Female; Humans; In Situ Nick-End Labeling; Ligands; Male; Middle Aged; Peroxisome proliferator-activated receptor γ; Pioglitazone; Polymorphism, Single-Stranded Conformational; Proliferation; Prostaglandin D2 - analogs & derivatives; Prostaglandin D2 - pharmacology; Receptors, Cytoplasmic and Nuclear - drug effects; Receptors, Cytoplasmic and Nuclear - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Thiazolidinediones - pharmacology; Transcription Factors - drug effects; Transcription Factors - metabolism; ALL; PGZ; BADGE; CDKIs; 15d-PGJ2; TGZ; Pioglitazone; SSCP; Proliferation; PPARγ; (Ph +) ALL; Peroxisome proliferator-activated receptor γ; TUNEL; CDKs; C T; LFS; Acute lymphocytic leukemia; NHRs; TZD; Apoptosis
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2003.07.005

This study examined the expression and structural intactness of peroxisome proliferator-activated receptor γ (PPARγ) in human acute lymphocytic leukemia (ALL) cells and determined the effect of PPARγ ligands on growth and apoptosis of these cells. We noted that all lymphocytic leukemia cell lines expressed PPARγ and no PPARγ mutations were found in these cell lines as indicated by SSCP analysis. Effect of the PPARγ ligands on the proliferation, differentiation and apoptosis of B type ALL cells was further examined. Treatment of these cells with the PPARγ 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 PPARγ-independent since several PPARγ 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 PPARγ ligands. This effect was partially caspase-dependent because a pan-caspase inhibitor partially reversed this effect. In conclusion, our results suggest that PPARγ ligands may offer a new therapeutic approach to aid in the treatment of ALL.