title: [Apoptosis of retinoic acid-resistant APL NB4-R1 cells induced by As4S4 and its molecular mechanism].
abstract: OBJECTIVE
  This study was to investigate the apoptosis-inducing effect of As(4)S(4) on the retinoic acid-resistant acute promyelocytic leukemia (APL) NB4-R1 cells and its potential mechanisms.
  
  
  METHODS
  The leukemia cell line NB4-R1 was cultured in vitro and divided into control group and treatment group. The apoptosis rate and cell cycle were detected by flow cytometry. The apoptotic DNA fragments were analyzed by agarose gel electrophoresis. The changes of BCL-2, BAX and Caspase-3 were determined by Western blot.
  
  
  RESULTS
  After NB4-R1 cells were treated with As(4)S(4)(25 µmol/L) for 0 h, 24 h, 48 h, the percentage of early apoptotic cells was obviously raised from 0% to 24.49% and 47.41%, the percentage of late apoptotic cells were elevated from 0.08% to 14.72% and 20.70%. Compared with control group, the DNA degradation revealed a characteristic DNA ladder during agarose gel electrophoresis after treatment for 24 h. The drug significantly induced an accumulation of the S phase cell population from 31.85% of the untreated cells to 42.53% and 55.12% treated with the different time whereas the NB4-R1 cells in G0/G1 phase decreased from 57.30% to 37.56% and 28.51%. As(4)S(4) could decrease the expression of BCL-2 and increase the level of BAX. Pro-caspase-3 could be cleaved into small active fragments under the apoptotic stimulation.
  
  
  CONCLUSIONS
  As(4)S(4) can efficiently induce NB4-R1 cell apoptosis, which may be related with the down-regulation of BCL-2 and the up-regulation of BAX, as well as the activation of Caspase-3.
authors: Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an 710061, Shaanxi Province, China.
authors: Yuan
authors: Y
authors: Wang
authors: Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an 710061, Shaanxi Province, China. E-mail: zhangmei@medmail.com.cn.
authors: Mei
authors: M
authors: Zhang
authors: Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an 710061, Shaanxi Province, China. E-mail: hepc@163.com.
authors: Peng-Cheng
authors: PC
authors: He
authors: Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an 710061, Shaanxi Province, China.
authors: Yan-Feng
authors: YF
authors: Liu
authors: Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an 710061, Shaanxi Province, China.
authors: Jun
authors: J
authors: Qi
authors: Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an 710061, Shaanxi Province, China.
authors: Xiao-Yan
authors: XY
authors: Cheng
authors: Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an 710061, Shaanxi Province, China.
authors: Hua-Chao
authors: HC
authors: Zhu
mesh_terms: D017209:Apoptosis; D053148:Caspase 3; D002453:Cell Cycle; D045744:Cell Line, Tumor; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D014212:Tretinoin; D015854:Up-Regulation
chemical_list: D014212:Tretinoin; C505407:CASP3 protein, human; D053148:Caspase 3