title: Emodin azide methyl anthraquinone derivative induced G0/ G1 arrest in HER2/neu-overexpressing MDA-MB-453 breast cancer cells.
abstract: OBJECTIVE
  Our previous data have shown that emodin azide methyl anthraquinone derivative (AMAD) triggered mitochondrial- dependent cell apoptosis involving caspase-8-mediated Bid cleavage, and induced proteasomal degradation of HER2/neu by blocking Her2/neu binding to Hsp90. In the present study, we futher investigated the effect of this compound on the cell cycle and related molecular mechanisms in HER2/neu-overexpressing MDA-MB-453 breast cancer cells.
  
  
  METHODS
  The cell cycle distribution was tested by flow cytometry. The expression of cell cycle-related proteins was determined by Western blot analysis; DNA agarose gel electrophoresis was used to examine the apoptosis of MDAMB- 453 cells induced by emodin AMAD.
  
  
  RESULTS
  After MDA-MB-453 cells were treated with different concentrations of emodin AMAD for 24 hrs, cells were arrested in G0/G1 phase, and the expression of G0/G1 related proteins c/Myc, Cyclin D1, CDK4 and p-Rb changed. DNA fragmentation appeared on the agarose gel in a concentration- dependent manner.
  
  
  CONCLUSIONS
  Emodin AMAD induced G0/G1 arrest in Her2/ neu-overexpressing MDA-MB-453 cancer cells. This G0/G1 arrest was associated with decreasing protein expression of c-Myc, Cyclin D1, CDK4, and p-Rb.
authors.affiliation: Medical College, Shanxi Datong University, Datong, Shanxi, People's Republic of China.
authors.forename: Yan-yan
authors.initials: YY
authors.lastname: Yan
authors.forename: Li-wu
authors.initials: LW
authors.lastname: Fu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Hong-shan
authors.initials: HS
authors.lastname: Ma
authors.forename: Cun-gen
authors.initials: CG
authors.lastname: Ma
authors.forename: Yong-ju
authors.initials: YJ
authors.lastname: Liang
authors.forename: Bin-yu
authors.initials: BY
authors.lastname: Liu
authors.forename: Jie-zhong
authors.initials: JZ
authors.lastname: Yu
authors.forename: Qiu-zhen
authors.initials: QZ
authors.lastname: Wu
authors.forename: Yi-min
authors.initials: YM
authors.lastname: Dong
mesh_terms: D000880:Anthraquinones / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001386:Azides / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000032:analysis; D051358:Cyclin-Dependent Kinase 4 / Q000032:analysis; D004642:Emodin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; D001386:Azides; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4; D004642:Emodin; D018719:Erb-b2 Receptor Tyrosine Kinases; C530789:6-azidomethyl-1-hydroxy-3,8-dimethoxy-9,10-anthraquinone; C530104:CCND1 protein, human; C508053:ERBB2 protein, human; C495900:CDK4 protein, human