Direct Short-Term Cytotoxic Effects of BIBR 1532 on Acute Promyelocytic Leukemia Cells Through Induction of p21 Coupled with Downregulation of c-Myc and hTERT Transcription

Acute promyelocytic leukemia (APL) is characterized by specific t(15;17), distinct morphologic picture, and clinical coagulopathy that contribute to the morbidity and mortality of the disease. This study aims to investigate the effects of antitelomerase compound BIBR1532 on APL cells (NB4). BIBR 153...

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Bibliographic Details
Published in:Cancer investigation 2012-01, Vol.30 (1), p.57-64
Main Authors: Bashash, D., Ghaffari, S. H., Zaker, F., Hezave, K., Kazerani, M., Ghavamzadeh, A., Alimoghaddam, K., Mosavi, S. A., Gharehbaghian, A., Vossough, P.
Format: Article
Language:English
Subjects:
Aminobenzoates - pharmacology
APL
Apoptosis - drug effects
bcl-2-Associated X Protein - metabolism
BIBR 1532
c-Myc
Caspase 3 - metabolism
Cell Line, Tumor
Cell Proliferation - drug effects
Cell Survival - drug effects
Dose-Response Relationship, Drug
Down-Regulation
hTERT
Humans
Leukemia, Promyelocytic, Acute - drug therapy
Leukemia, Promyelocytic, Acute - genetics
Leukemia, Promyelocytic, Acute - metabolism
Leukemia, Promyelocytic, Acute - pathology
Naphthalenes - pharmacology
NB4
Proto-Oncogene Proteins c-bcl-2 - metabolism
Proto-Oncogene Proteins c-myc - genetics
Proto-Oncogene Proteins c-myc - metabolism
rho GTP-Binding Proteins - genetics
rho GTP-Binding Proteins - metabolism
Telomerase
Telomerase - antagonists & inhibitors
Telomerase - genetics
Telomerase - metabolism
Transcription, Genetic - drug effects
Transcriptional Activation - drug effects
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Summary:Acute promyelocytic leukemia (APL) is characterized by specific t(15;17), distinct morphologic picture, and clinical coagulopathy that contribute to the morbidity and mortality of the disease. This study aims to investigate the effects of antitelomerase compound BIBR1532 on APL cells (NB4). BIBR 1532 exerts a direct short-term growth suppressive effect in a concentration-dependent manner probably through downregulation of c-Myc and hTERT expression. Our results also suggest that induction of p21 and subsequent disturbance of Bax/Bcl-2 balanced ratio as well as decreased telomerase activity may be rational mechanisms for the potent/direct short-term cytotoxicity of high doses of BIBR1532 against NB4 cells.
ISSN:0735-7907
1532-4192
DOI:10.3109/07357907.2011.629378