title: 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.affiliation: Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences.
authors.forename: D
authors.initials: D
authors.lastname: Bashash
authors.forename: S H
authors.initials: SH
authors.lastname: Ghaffari
authors.forename: F
authors.initials: F
authors.lastname: Zaker
authors.forename: K
authors.initials: K
authors.lastname: Hezave
authors.forename: M
authors.initials: M
authors.lastname: Kazerani
authors.forename: A
authors.initials: A
authors.lastname: Ghavamzadeh
authors.forename: K
authors.initials: K
authors.lastname: Alimoghaddam
authors.forename: S A
authors.initials: SA
authors.lastname: Mosavi
authors.forename: A
authors.initials: A
authors.lastname: Gharehbaghian
authors.forename: P
authors.initials: P
authors.lastname: Vossough
mesh_terms: D062365:Aminobenzoates / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009281:Naphthalenes / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D062365:Aminobenzoates; C458523:BIBR 1532; C489427:MYC protein, human; D009281:Naphthalenes; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D051028:bcl-2-Associated X Protein; C509186:TERT protein, human; D019098:Telomerase; D053148:Caspase 3; D020741:rho GTP-Binding Proteins