title: Curcumin suppresses malignant glioma cells growth and induces apoptosis by inhibition of SHH/GLI1 signaling pathway in vitro and vivo.
abstract: OBJECTIVE
  To study the role of curcumin on glioma cells via the SHH/GLI1 pathway in vitro and vivo.
  
  
  METHODS
  The effects of curcumin on proliferation, migration, apoptosis, SHH/GLI1 signaling, and GLI1 target genes expression were evaluated in multiple glioma cell lines in vitro. A U87-implanted nude mice model was used to study the role of curcumin on tumor volume and the suppression efficacy of GLI1.
  
  
  RESULTS
  Curcumin showed cytotoxic effects on glioma cell lines in vitro. Both mRNA and protein levels of SHH/GLI1 signaling (Shh, Smo, GLI1) were downregulated in a dose- and time-dependent manner. Several GLI1-dependent target genes (CyclinD1, Bcl-2, Foxm1) were also downregulated. Curcumin treatment prevented GLI1 translocating into the cell nucleus and reduced the concentration of its reporter. Curcumin suppressed cell proliferation, colony formation, migration, and induced apoptosis which was mediated partly through the mitochondrial pathway after an increase in the ratio of Bax to Bcl2. Intraperitoneal injection of curcumin in vivo reduced tumor volume, GLI1 expression, the number of positively stained cells, and prolonged the survival period compared with the control group.
  
  
  CONCLUSIONS
  This study shows that curcumin holds a great promise for SHH/GLI1 targeted therapy against gliomas.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Wen-Zhong
authors.initials: WZ
authors.lastname: Du
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Wang
authors.forename: Xing-Yin
authors.initials: XY
authors.lastname: Piao
authors.forename: Yu-Qiong
authors.initials: YQ
authors.lastname: Cui
authors.forename: Ling-Chao
authors.initials: LC
authors.lastname: Chen
authors.forename: Xu-Hui
authors.initials: XH
authors.lastname: Lei
authors.forename: Xu
authors.initials: X
authors.lastname: Sun
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: Han-Bing
authors.initials: HB
authors.lastname: Wang
authors.forename: Xian-Feng
authors.initials: XF
authors.lastname: Li
authors.forename: Dong-Bo
authors.initials: DB
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Zhe-Feng
authors.initials: ZF
authors.lastname: Zhao
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Yong-Li
authors.initials: YL
authors.lastname: Li
authors.forename: Chuan-Lu
authors.initials: CL
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003474:Curcumin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects*; D014157:Transcription Factors / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000071676:Zinc Finger Protein GLI1
chemical_list: D000970:Antineoplastic Agents; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C509239:SHH protein, human; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D003474:Curcumin
keywords: Apoptosis; Curcumin; GLI1; Malignant glioma; Proliferation