Troglitazone Inhibits Cell Growth and Induces Apoptosis of B-Cell Acute Lymphoblastic Leukemia Cells with t(14;18)
| Autor: | Shunichi Kumagai, Katsuyasu Saigo, Makoto Hashimoto, Mariko Takenokuchi, S. Kawano, Tamio Koizumi, Y. Nakamachi, T Fujioka, E Tatsumi |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Cell cycle checkpoint Adolescent Blotting Western Down-Regulation Antineoplastic Agents Apoptosis Biology Ligands Translocation Genetic Proto-Oncogene Proteins c-myc Troglitazone Downregulation and upregulation Cell Line Tumor medicine Humans Chromans Aged Chromosomes Human Pair 14 Regulation of gene expression Dose-Response Relationship Drug Gene Expression Regulation Leukemic Reverse Transcriptase Polymerase Chain Reaction Cell growth G1 Phase Hematology General Medicine Prognosis Burkitt Lymphoma Molecular biology PPAR gamma Nuclear receptor Cell culture Female Thiazolidinediones Chromosomes Human Pair 18 medicine.drug |
| Zdroj: | Acta Haematologica. 116:30-40 |
| ISSN: | 1421-9662 0001-5792 |
| DOI: | 10.1159/000092345 |
| Popis: | Peroxisome proliferator-activated receptor-γ (PPARγ), a member of the nuclear receptor superfamily, has been detected in several human leukemia cells. Recent studies reported that PPARγ ligands inhibit cell proliferation and induce apoptosis in both normal and malignant B-lineage cells. We investigated the expression of PPARγ and the effects of PPARγ ligands on UTree-O2, Bay91 and 380, three B-cell acute lymphoblastic leukemia (B-ALL) cell lines with t(14;18), which show a poor prognosis, accompanying c-myc abnormality. Western blot analysis identified expression of PPARγ protein and real-time PCR that of PPARγ mRNA on the three cell lines. Troglitazone (TGZ), a synthetic PPARγ ligand, inhibited cell growth in these cell lines in a dose-dependent manner, which was associated with G1 cell cycle arrest and apoptosis. We also found this effect PPARγ independent since PPARγ antagonists failed to reverse this effect. We assessed the expression of c-myc, an apoptosis-regulatory gene, since c-myc abnormality was detected in most B-ALL cells with t(14;18). TGZ was found to dose-dependently downregulate the expression of c-myc mRNA and c-myc protein in the three cell lines. These results suggest that TGZ inhibits cell growth via induction of G1 cell cycle arrest and apoptosis in these cell lines and that TGZ-induced apoptosis, at least in part, may be related to the downregulation of c-myc expression. Moreover, the downregulation of c-myc expression by TGZ may depend on a PPARγ-independent mechanism. Further studies indicate that PPARγ ligands may serve as a therapeutic agent in B-ALL with t(14;18). |
| Databáze: | OpenAIRE |
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