title: Ellagic acid inhibits proliferation and induces apoptosis in human glioblastoma cells.
abstract: OBJECTIVE
  To investigate the anticancer activity of ellagic acid (EA) in U251 human glioblastoma cells and its possible molecular mechanism.
  
  
  METHODS
  The cells were treated with EA at various concentrations for different time periods. Cell viability and cell proliferation were detected by cell counting kit-8(CCK-8) assay and live/dead assay respectively. Cell apoptosis were measured with Annexin V-FITC/PI double staining method by flow cytometry and Mitochondrial membrane potential assay separately. Cell cycle was measured with PI staining method by flow cytometry. The expressions of Bcl-2, Survivin, XIAP, Caspase-3, Bax, JNK, p-JNK, ERK1/2, p-ERK1/2, p38, p-p38, DR4, DR5, CHOP and GRP78-related proteins were detected by western blot after EA treatment.
  
  
  RESULTS
  Cell viability and proliferation of glioblastoma cells treated with EA were significantly lower than the control group. EA caused robust apoptosis of the glioblastoma cells compared to the control group. EA significantly decreased the proportion at G0/G1 phases of cell cycling accompanied by increased populations at S phase in U251 cell lines. And the expressions of anti-apoptotic proteins were dramatically down-regulated.
  
  
  CONCLUSIONS
  Ellagic acid potentially up-regulated DR4, DR5 and MAP kinases (JNK, ERK1/2 and p38). EA also caused significant increase in the expressions of CHOP and GRP78. Our findings suggest that EA would be beneficial for the treatment of glioblastoma.
authors.affiliation: Department of Neurosurgery, Wuhan University, Hubei Province, China.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Wuhan University, Hubei Province, China.
authors.forename: Qianxue
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Wuhan University, Hubei Province, China.
authors.forename: Baohui
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Wuhan University, Hubei Province, China.
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Wuhan University, Hubei Province, China.
authors.forename: Yingqiu
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Neurosurgery, Wuhan University, China.
authors.forename: Bangkun
authors.initials: B
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004610:Ellagic Acid / Q000378:metabolism / Q000494:pharmacology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005909:Glioblastoma / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051742:Transcription Factor CHOP / Q000187:drug effects / Q000378:metabolism
chemical_list: C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D051742:Transcription Factor CHOP; D004610:Ellagic Acid; D053148:Caspase 3