title: [Inhibitory effect of alantolactone on the proliferation of K562/ADR cells and its mechanism].
abstract: OBJECTIVE
  To explore the inhibitory effect of alantolactone on the proliferation of adriamycin-resistant human chronic myelogenous leukemia cell line K562/ADR cells and its mechanism.
  
  
  METHODS
  K562/ADR cells were treated with various concentrations of alantolactone (0, 1, 2, 4, 6, 8, and 10 μmol/L) for different time points. Cell viability was analyzed with MTT assay. The effect of alantolactone on the apoptosis of K562/ADR cells was measured by flow cytometry. The expression of apoptosis-related proteins after treatment with alantolactone was analyzed using Western blot.
  
  
  RESULTS
  Alantolactone could effectively inhibit the proliferation of K562/ADR cells in dose- and time- dependent manner, the IC50 value of alantolactone treatment of K562/ADR cells for 24 h was 4.7 μmol/L (P<0.05). Flow cytometric analysis displayed that the apoptotic rates were 1.35%, 16.91%, 29.61% and 46.26%, respectively, after treatment with alantolactone at 0, 2.5, 5 and 7.5 μmol/L. Meanwhile, the expression of Bcl-2 and BCR-ABL proteins were significantly decreased and that of Bax, cytochrome C, cleaved-caspase-9, cleaved-caspase-3 and cleaved-PARP increased by alantolactone treatment.
  
  
  CONCLUSIONS
  Alantolactone had obvious inhibitory effect on the proliferation of K562/ADR cells through the caspase dependent mitochondrial(or intrinsic)apoptotic pathway.
authors.affiliation: Department of Laboratory Hematology, College of Laboratory Medicine, Dalian Medical University, Dalian 116044, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Laboratory Hematology, College of Laboratory Medicine, Dalian Medical University, Dalian 116044, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Laboratory Hematology, College of Laboratory Medicine, Dalian Medical University, Dalian 116044, China.
authors.forename: Jiangzhou
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Laboratory Hematology, College of Laboratory Medicine, Dalian Medical University, Dalian 116044, China.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Laboratory Hematology, College of Laboratory Medicine, Dalian Medical University, Dalian 116044, China.
authors.forename: Meiyan
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Laboratory Hematology, College of Laboratory Medicine, Dalian Medical University, Dalian 116044, China.
authors.forename: Xiuxiang
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Laboratory Hematology, College of Laboratory Medicine, Dalian Medical University, Dalian 116044, China.
authors.forename: Tonghui
authors.initials: T
authors.lastname: Ma
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D007783:Lactones / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D045787:Sesquiterpenes, Eudesmane / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D007783:Lactones; D019253:Proto-Oncogene Proteins c-bcl-2; D045787:Sesquiterpenes, Eudesmane; D051028:bcl-2-Associated X Protein; D016044:Fusion Proteins, bcr-abl; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; C004363:alantolactone