title: Telomerase inhibition by non-nucleosidic compound BIBR1532 causes rapid cell death in pre-B acute lymphoblastic leukemia cells.
abstract: Since unlimited proliferative potential has been identified as a major and, to date, therapeutically unexploited phenotypic hallmark of cancer, telomere maintenance mechanisms have been proposed as potential targets for new anticancer interventions. This study was aimed to investigate the effects of BIBR1532, the lead compound of non-nucleosidic inhibition of telomerase, on pre-B acute lymphoblastic leukemia (ALL) cells. BIBR1532 caused rapid cell death in Nalm-6 cells probably through transcriptional suppression of survivin-mediated c-Myc and human telomerase reverse transcriptase (hTERT) expression in a concentration-dependent manner. Moreover, our results also suggest that induced p73, up-regulated Bax/Bcl-2 molecular ratio and subsequent activation of caspase-3 may contribute to a direct short-term cytotoxic effect of high doses of BIBR1532, independent of long-term substantial telomere erosion-mediated cell cycle arrest.
authors.affiliation: Department of Hematology, Faculty of Allied Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Davood
authors.initials: D
authors.lastname: Bashash
authors.forename: Seyed H
authors.initials: SH
authors.lastname: Ghaffari
authors.forename: Rooholah
authors.initials: R
authors.lastname: Mirzaee
authors.forename: Kamran
authors.initials: K
authors.lastname: Alimoghaddam
authors.forename: Ardeshir
authors.initials: A
authors.lastname: Ghavamzadeh
mesh_terms: D062365:Aminobenzoates / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D062365:Aminobenzoates; C458523:BIBR 1532; C107489:BIRC5 protein, human; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; C489427:MYC protein, human; D009281:Naphthalenes; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D000077022:Survivin; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D019098:Telomerase; D053148:Caspase 3