title: [Isoalantolactone Inhibits Proliferation of K562/A02 Cells through Caspase-Dependent Apoptotic Pathway].
abstract: OBJECTIVE
  To explore the apoptosis-inducing effects of isoalantolactone on chronic myeloid leukemia drug-resistant cell line K562/A02.
  
  
  METHODS
  K562/A02 cells were treated with 0, 6.25, 12.5, 25, 50, and 100 µmol/L isoalantolactone for 12 h, 24 h, and 48 h. The cell viability was analyzed with CCK8 assay. The effects of isoalantolactone on mitochondrial membrane potential (MMP), reactive oxygen species(ROS) and apoptosis of K562/A02 cells were measured by flow cytometry. The apoptosis related proteins were analyzed by using Western blot after treatment with isoalantolactone.
  
  
  RESULTS
  Isoalantolactone effectively inhibited the proliferation of K562/A02 cells in dose- and time-dependent manner, the IC50value of isoalantolactone in K562/A02 cells at 24 h was about (15±1.42) µmol/L (P<0.05). Flow cytometric analysis displayed that after treatment of K562/A02 cells with 0, 10, 15, and 20 µmol/L of isoalantolactone, apoptotic rate were 1.35±0.52%, 18.07±4.03%, 27.53±3.01%, and 34.99±4.91%, respectively, mitochondrial membrane potential was 96.42±3.59%, 74.25±6.91%, 60.97±5.69%, and 31.28±4.95%, respectively. Otherwise, isoalantolactone induced accumulation of intracellular reactive oxygen species(ROS) in K562/A02 cells (5.03±1.43%, 17.55±3.85%, 32.09±3.23%, and 44.38±5.92%). Meanwhile, isoalantolactone significantly down-regulated the expression of BCL-2 protein and up-regulated the expression of BAX, cytochrome C, cleaved-caspase-9, cleaved-caspase-3, and cleaved-PARP.
  
  
  CONCLUSIONS
  Isoalantolactone significantly inhibits K562/A02 cell proliferation mainly via caspase-dependent apoptotic pathway.
authors.affiliation: Department of Infectious Diseases, The Second Hospital Affiliated to Dalian Medical University, Dalian 116023.
authors.forename: Yong-Hai
authors.initials: YH
authors.lastname: Guan
authors.affiliation: Zhuanghe Blood Donation Office, Zhuanghe 116400, Liaoning Province, China.
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratorial Examination, The Second Hospital Affiliated to Dalian Medical University, Dalian 116023, Liaoning Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Clinical Laboratorial Examination, The Second Hospital Affiliated to Dalian Medical University, Dalian 116023, Liaoning Province, China. E-mail: yangchunhui627@163.com.
authors.forename: Chun-Hui
authors.initials: CH
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D020169:Caspases / Q000187:drug effects*; D049109:Cell Proliferation; D006801:Humans; D020014:K562 Cells; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D012717:Sesquiterpenes; C032787:isoalantolactone; D020169:Caspases