Peroxisome proliferator-activated receptor activation increases imatinib uptake and killing of chronic myeloid leukemia cells
| Autor: | Gemma Austin, Lihui Wang, Athina Giannoudis, Richard E. Clark |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
Cancer Research CD34 Peroxisome proliferator-activated receptor Antineoplastic Agents Biology Piperazines Mice Downregulation and upregulation hemic and lymphatic diseases Leukemia Myelogenous Chronic BCR-ABL Positive Genetics medicine Animals Humans PPAR alpha Receptor neoplasms Molecular Biology chemistry.chemical_classification Gene Expression Regulation Leukemic Myeloid leukemia Imatinib Cell Biology Hematology Up-Regulation PPAR gamma Hepatocyte nuclear factors Pyrimidines chemistry Liver Cell culture Benzamides Cancer research Hepatocytes Imatinib Mesylate Female K562 Cells medicine.drug Octamer Transcription Factor-1 |
| Zdroj: | Experimental hematology. 40(10) |
| ISSN: | 1873-2399 |
| Popis: | Low pretreatment expression of the imatinib uptake transporter human organic cation transporter 1 (hOCT1) is associated with inferior complete cytogenetic response rates, progression-free survival, and overall survival in imatinib-treated chronic myeloid leukemia (CML). Upregulation of hOCT1 can therefore increase the uptake of imatinib. The hOCT1 gene is transactivated by hepatocyte nuclear factor 4α in human liver, and peroxisome proliferator–activated receptors (PPAR) α and γ activation increases OCT1 expression in mouse hepatocytes. Here we report that no isoform of hepatocyte nuclear factor 4α is expressed in CML lines or in CML primary cells. In contrast, both PPARα and γ were expressed in all CML cell lines and primary cells studied. PPARα agonist treatment increased imatinib killing of CML KCL22 cells and primitive CD34 + cells, and also upregulates hOCT1 gene expression and increases imatinib uptake into KCL22 cells and primary cells. PPARα agonists might potentially be of clinical use in CML patients failing imatinib. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect