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.

Abstract	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.
Authors	D Bashash, S H Ghaffari, F Zaker, K Hezave, M Kazerani, A Ghavamzadeh, K Alimoghaddam, S A Mosavi, A Gharehbaghian, P Vossough
Journal	Cancer investigation (Cancer Invest) Vol. 30 Issue 1 Pg. 57-64 (Jan 2012) ISSN: 1532-4192 [Electronic] England
PMID	22236190 (Publication Type: Journal Article)
Chemical References	Aminobenzoates BIBR 1532 MYC protein, human Naphthalenes Proto-Oncogene Proteins c-bcl-2 Proto-Oncogene Proteins c-myc bcl-2-Associated X Protein TERT protein, human Telomerase Caspase 3 rho GTP-Binding Proteins
Topics	Aminobenzoates (pharmacology) Apoptosis (drug effects) Caspase 3 (metabolism) Cell Line, Tumor Cell Proliferation (drug effects) Cell Survival (drug effects) Dose-Response Relationship, Drug Down-Regulation Humans Leukemia, Promyelocytic, Acute (drug therapy, genetics, metabolism, pathology) Naphthalenes (pharmacology) Proto-Oncogene Proteins c-bcl-2 (metabolism) Proto-Oncogene Proteins c-myc (genetics, metabolism) Telomerase (antagonists & inhibitors, genetics, metabolism) Transcription, Genetic (drug effects) Transcriptional Activation (drug effects) bcl-2-Associated X Protein (metabolism) rho GTP-Binding Proteins (genetics, metabolism)

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