title: Cytotoxic effect of arsenic trioxide on acute promyelocytic leukemia cells through suppression of NFkβ-dependent induction of hTERT due to down-regulation of Pin1 transcription.
abstract: Acute promyelocytic leukemia (APL) is characterized by specific t(15;17), distinct morphologic picture, and clinical coagulopathy that contributes to the morbidity and mortality of the disease. This study was purposed to dissect the molecular mechanisms underlying telomerase-dependent  arsenic trioxide (ATO)-induced cytotoxic and anti-proliferative effects in NB4 cells. ATO exposure was associated with transcriptional repression of Pin1, survivin, c-Myc, hTERT, and PinX1 along with an expressive enhancement in p73 mRNA level. Moreover, ATO treatment suppressed cell growth,  viability and metabolic activity, exerted apoptosis, hindered telomerase activity, shortened telomere length, and dampened NF-κB activation. On aggregate, these issues indicate that ATO might preempt cell growth and proliferation in NB4 cells through suppression of Pin1-mediated NF-κB-dependent  stimulation of telomerase and survivin.
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. shghaffari200@yahoo.com
authors.forename: Seyed H
authors.initials: SH
authors.lastname: Ghaffari
authors.forename: Majid
authors.initials: M
authors.lastname: Momeny
authors.forename: Davood
authors.initials: D
authors.lastname: Bashash
authors.forename: Roohollah
authors.initials: R
authors.lastname: Mirzaei
authors.forename: Ardeshir
authors.initials: A
authors.lastname: Ghavamzadeh
authors.forename: Kamran
authors.initials: K
authors.lastname: Alimoghaddam
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics; D015536:Down-Regulation; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D016259:Genes, myc; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009687:Nuclear Proteins / Q000235:genetics; D010087:Oxides / Q000494:pharmacology* / Q000633:toxicity; D019696:Peptidylprolyl Isomerase / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects; D000077022:Survivin; D019098:Telomerase / Q000235:genetics*; D059506:Telomere Shortening / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D001152:Arsenicals; C107489:BIRC5 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009687:Nuclear Proteins; D010087:Oxides; C440808:PINX1 protein, human; D000077022:Survivin; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C509186:TERT protein, human; D019098:Telomerase; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; D000077237:Arsenic Trioxide