| Centrosome aberrations and G1 phase arrest after in vitro and in vivo treatment with the SRC/ABL inhibitor dasatinib. | |
| | |
MedLine Citation:
|
PMID: 18519516 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: Dasatinib is a multitargeted inhibitor of ABL, the SRC family, and other tyrosine kinases. We sought to evaluate the effects of this drug on cell proliferation, centrosomes, mitotic spindles, and cell cycle progression in vitro and in vivo. DESIGN AND METHODS: Human dermal fibroblasts, Chinese hamster cells, human osteosarcoma cells, and blood and bone marrow mononuclear cells from 32 patients with chronic myeloid leukemia, gastrointestinal stromal tumor, and systemic mastocytosis as well as from six healthy individuals were investigated. The effects of dasatinib were compared with those of the ABL inhibitors imatinib and nilotinib, the SRC inhibitor PP2, and the ABL/LYN inhibitor INNO-406. RESULTS: Dasatinib induced G(1) phase arrest in all cell lines and this was associated with a decline in cyclin D1 levels. In vitro, centrosomal aberrations, a decrease of mitotic spindles, and G(1) phase arrest were observed. In patients, centrosome alterations were found in a median of 17% (range, 10-22%) of cells with a decrease of spindles in 8/18 patients. In comparison, imatinib, nilotinib and PP2 led to centrosome aberrations without G(1) phase arrest. INNO-406 was associated with centrosome aberrations and cell cycle arrest in G(1) phase. CONCLUSIONS: Dasatinib blocks the G(1)/S transition and inhibits cell growth. It induces centrosomal aberrations and a decrease of mitotic spindles. The effects suggest an involvement of SRC and ABL inhibition. |
| | |
Authors:
|
Alice Fabarius; Michelle Giehl; Blanka Rebacz; Alwin Krämer; Oliver Frank; Claudia Haferlach; Peter Duesberg; Rüdiger Hehlmann; Wolfgang Seifarth; Andreas Hochhaus |
Related Documents
:
|
1353706 - Combined antimicrotubule activity of estramustine and taxol in human prostatic carcinom... 10679396 - Cell-cycle checkpoints that ensure coordination between nuclear and cytoplasmic events ... 17267256 - Localization of a drosophila drip-like aquaporin in the malpighian tubules of the house... 9248996 - Process of dispersion and fragmentation of golgi complex by microtubule bundles formed ... 2833576 - Generation of human myogenic cell lines by the transformation of primary culture with o... 3279056 - Joint oxygen-glucose deprivation as the cause of necrosis in a tumor analog. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-06-02 |
Journal Detail:
|
Title: Haematologica Volume: 93 ISSN: 1592-8721 ISO Abbreviation: Haematologica Publication Date: 2008 Aug |
Date Detail:
|
Created Date: 2008-08-01 Completed Date: 2008-10-09 Revised Date: 2008-11-21 |
Medline Journal Info:
|
Nlm Unique ID: 0417435 Medline TA: Haematologica Country: Italy |
Other Details:
|
Languages: eng Pagination: 1145-54 Citation Subset: IM |
Affiliation:
|
III. Medizinische Klinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Wiesbadener Strasse 7-11, 68305 Mannheim, Germany. alice.fabarius@med3.ma.uni-heidelberg.de |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Antineoplastic Agents / pharmacology* Bone Marrow Cells / drug effects, pathology CHO Cells Cell Division / drug effects Cell Line, Tumor Centrosome / drug effects* Cricetinae Cricetulus Fibroblasts / physiology* G1 Phase / drug effects, genetics* Genes, abl / drug effects* Genes, src / drug effects* Humans Leukemia, Myelogenous, Chronic, BCR-ABL Positive / blood, drug therapy, pathology Osteosarcoma Piperazines / pharmacology*, therapeutic use Pyrimidines / pharmacology*, therapeutic use Skin Physiological Phenomena |
| Chemical | |
Reg. No./Substance:
|
0/Antineoplastic Agents; 0/Piperazines; 0/Pyrimidines; 152459-95-5/imatinib |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Chronic preclinical safety evaluation of Hematide, a pegylated peptidic erythropoiesis stimulating a...
Next Document: Development of hypogammaglobulinemia in patients treated with imatinib for chronic myeloid leukemia ...