In vitro inhibitory effects of imatinib mesylate on stromal cells and hematopoietic progenitors from bone marrow
| Autor: | M.C. Santos-Silva, Marcio Alvarez-Silva, Cidônia de Lourdes Vituri, M.A. Licínio, P.B. Soares, T.S. Jeremias |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Pathology medicine.medical_specialty Stromal cell Physiology Cell Survival Myelosuppression Immunology Biophysics Ocean Engineering Antineoplastic Agents Biology Biochemistry Piperazines Colony-Forming Units Assay Mice medicine Animals General Pharmacology Toxicology and Pharmaceutics Progenitor cell Clonogenic assay lcsh:QH301-705.5 Cells Cultured Bone marrow stromal cell Cell Proliferation lcsh:R5-920 Cell growth General Neuroscience Biomedical Sciences Mesenchymal Stem Cells Cell Biology General Medicine Fibroblasts Hematopoietic Stem Cells Immunohistochemistry Haematopoiesis Imatinib mesylate medicine.anatomical_structure Pyrimidines lcsh:Biology (General) Hematopoietic progenitors Benzamides Cancer research Bone marrow lcsh:Medicine (General) Tyrosine kinase |
| Zdroj: | Brazilian Journal of Medical and Biological Research, Volume: 46, Issue: 1, Pages: 39-51, Published: 25 SEP 2012 Brazilian Journal of Medical and Biological Research v.46 n.1 2013 Brazilian Journal of Medical and Biological Research Associação Brasileira de Divulgação Científica (ABDC) instacron:ABDC Brazilian Journal of Medical and Biological Research, Vol 46, Iss 1, Pp 39-51 (2013) |
| Popis: | Imatinib mesylate (IM) is used to treat chronic myeloid leukemia (CML) because it selectively inhibits tyrosine kinase, which is a hallmark of CML oncogenesis. Recent studies have shown that IM inhibits the growth of several non-malignant hematopoietic and fibroblast cells from bone marrow (BM). The aim of the present study was to evaluate the effects of IM on stromal and hematopoietic progenitor cells, specifically in the colony-forming units of granulocyte/macrophage (CFU-GM), using BM cultures from 108 1.5- to 2-month-old healthy Swiss mice. The results showed that low concentrations of IM (1.25 µM) reduced the growth of CFU-GM in clonogenic assays. In culture assays with stromal cells, fibroblast proliferation and α-SMA expression by immunocytochemistry analysis were also reduced in a concentration-dependent manner, with a survival rate of approximately 50% with a dose of 2.5 µM. Cell viability and morphology were analyzed using MTT and staining with acrydine orange/ethidium bromide. Most cells were found to be viable after treatment with 5 µM IM, although there was gradual growth inhibition of fibroblastic cells while the number of round cells (macrophage-like cells) increased. At higher concentrations (15 µM), the majority of cells were apoptotic and cell growth ceased completely. Oil red staining revealed the presence of adipocytes only in untreated cells (control). Cell cycle analysis of stromal cells by flow cytometry showed a blockade at the G0/G1 phases in groups treated with 5-15 µM. These results suggest that IM differentially inhibits the survival of different types of BM cells since toxic effects were achieved. |
| Databáze: | OpenAIRE |
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