title: Synergism between carnosic acid and arsenic trioxide on induction of acute myeloid leukemia cell apoptosis is associated with modulation of PTEN/Akt signaling pathway.
abstract: OBJECTIVE
  To investigate the synergistic effects of carnosic acid (CA) with arsenic trioxide (As₂O₃) on proliferation and apoptosis in HL-60 human myeloid leukemia cells, and the major cellular signaling pathway involved in these effects.
  
  
  METHODS
  HL-60 cellular proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis. Cell cycle distribution and apoptosis were monitored by flow cytometry. The activation of casepase-9, Bcl-2-associated agonist of cell death (BAD), p-BAD, p27, phosphatase and tensin homolog deleted on chromosome ten (PTEN), Akt, p-Akt was assessed by Western blot analysis. The expression of PTEN mRNA was tested by reverse transcription polymerase chain reaction (RT-PCR) analysis.
  
  
  RESULTS
  CA reduced HL-60 cell viability in a dose- and time-dependent manner, and induced G1 arrest and apoptosis. Moreover, CA upregulated PTEN expression, blocked the Akt signaling pathway, subsequently inhibited phosphorylation of BAD, reactivated caspase-9, and elevated levels of p27. CA also augmented these effects of As₂O₃.
  
  
  CONCLUSIONS
  CA might be a novel candidate of the combination therapy for leukemia treatment; these effects were apparently associated with the modulation of PTEN/Akt signaling pathway.
authors.affiliation: Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Wang
authors.forename: Wei-hong
authors.initials: WH
authors.lastname: Cong
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
authors.forename: Xiang-xin
authors.initials: XX
authors.lastname: Li
authors.forename: Xue-liang
authors.initials: XL
authors.lastname: Chen
authors.forename: Xiao-ning
authors.initials: XN
authors.lastname: Yu
authors.forename: Hao
authors.initials: H
authors.lastname: Li
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001483:Base Sequence; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D017931:DNA Primers; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D010087:Oxides / Q000494:pharmacology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D045784:Abietanes; D001152:Arsenicals; D017931:DNA Primers; D010087:Oxides; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C018381:salvin; D000077237:Arsenic Trioxide