title: Parthenolide reduces gene transcription of prosurvival mediators in U937 cells.
abstract: In acute myeloid leukemia (AML) the functional abnormalities of osteopontin (OPN), NF-kB, PI3K/AKT/mTOR/PTEN pathway or β-catenin have been considered.
  
  
  
  To analyze the response of U937 cells to parthenolide (PTL) through the involvement of expression of OPN protein, RelB, AKT1, mTOR, PTEN and β-catenin genes.
  
  
  
  The U937 cells were treated with PTL at concentrations of 4 μM (IC25) or 6 μM (IC50) and with OPN siRNA for MTT assay and colony forming assay. Western blot analysis using antibodies against OPN was performed with lysates of PTL-treated cells. Quantitative real-time polymerase chain reaction was performed using primers for OPN siRNA, RelB, AKT1, mTOR, PTEN and β-catenin.
  
  
  
  PTL reduces OPN protein level and down-regulates RelB mRNA in U937 cell line. Suppression of OPN with siRNA increases the cytotoxic effects of PTL. Also, mRNA expression of AKT1, mTOR, PTEN, and β-catenin decreases with PTL or OPN siRNA.
  
  
  
  Sensitivity of U937 cells to PTL can be associated with the reduction in expression of prosurvival mediators.
authors.affiliation: Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran 14176-13151, Iran.
authors.forename: S
authors.initials: S
authors.lastname: Mohammadi
authors.affiliation: Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin 34157-38477, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Zahedpanah
authors.affiliation: Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran 14176-13151, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Nikbakht
authors.affiliation: Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran 14665-1157, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Shaiegan
authors.affiliation: Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran 14176-13151, Iran.
authors.forename: Ghaffari
authors.initials: G
authors.lastname: Hamidollah
authors.affiliation: Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran 14665-1157, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Nikugoftar
authors.affiliation: Department of Biochemistry and Genetics, Qazvin University of Medical Sciences, Qazvin 34157-38477, Iran.
authors.forename: B
authors.initials: B
authors.lastname: Rahmani
authors.affiliation: Department of Biochemistry and Genetics, Qazvin University of Medical Sciences, Qazvin 34157-38477, Iran.
authors.forename: D
authors.initials: D
authors.lastname: Hamedi Asl
mesh_terms: D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012717:Sesquiterpenes / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051841:Transcription Factor RelB / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014410:Tumor Stem Cell Assay / Q000379:methods*; D020298:U937 Cells; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; C497593:RELB protein, human; D012717:Sesquiterpenes; D051176:beta Catenin; D053495:Osteopontin; D051841:Transcription Factor RelB; C002669:parthenolide; C546842:MTOR protein, human; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human