title: Honokiol induces cell cycle arrest and apoptosis via p53 activation in H4 human neuroglioma cells.
abstract: OBJECTIVE
  To investigate the signal pathway of honokiol-induced apoptosis in H4 human neuroglioma cells and to evaluate whether p53 signaling and cell cycle arrest were involved in honokiol-treated H4 human neuroglioma cells.
  
  
  METHODS
  The cell viability was detected by the CCK8 assay. The cell apoptosis was assessed by annexin V-PI double-labeling staining and hoechst 33342 staining. The protein expression of cell cycle regulators and tumor suppressors were analyzed by western blotting.
  
  
  RESULTS
  Treatment of H4 human neuroglioma cells with honokiol induced cell death in a dose-and time-dependent manner by using CCK8 assay. Consistent with the CCK8 assay, the flow cytometry results showed that the proportion of the apoptosis cells increased after honokiol when compared with untreated group. Moreover, H4 human neuroglioma cells exposed to honokiol, resulted in an accumulation of cells in S and G2/M phase. Apoptotic bodies were clearly observed in human neuroglioma cells when treated with honokiol and then stained with Hoechst 33342. The expression of Cyclin B1, CDC2 and cdc25C were downregulated, however, the expression of p-CDC2 and p-cdc25c was significantly upregulated when the neuroglioma cells were exposed to honokiol. Moreover, p53, p21 and Bax/Bcl-2 were significantly upregulated by honokiol treatment.
  
  
  CONCLUSIONS
  These results confirmed that honokiol could induce apoptosis in human neuroglioma cells, the underlying molecular mechanisms, at least partially, through activation p53 signaling and induction of cell cycle arrest.
authors.affiliation: Department of Neurosurgery, First Hospital of Jilin University Changchun 130021, China.
authors.forename: Yun-Bao
authors.initials: YB
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Peking Union Medical College Beijing 100730, China.
authors.forename: Xin-Jie
authors.initials: XJ
authors.lastname: Bao
authors.affiliation: Department of Neurosurgery, First Hospital of Jilin University Changchun 130021, China.
authors.forename: Song-Bai
authors.initials: SB
authors.lastname: Xu
authors.affiliation: Department of Anatomy, College of Basic Medical Sciences, Jilin University Changchun 130021, China.
authors.forename: Xing-Dong
authors.initials: XD
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, College of Basic Medical Sciences, Jilin University Changchun 130021, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Liu
keywords: Honokiol; cell cycle arrest; neuroglioma; p53/p21