title: Curcumin-induced HDAC inhibition and attenuation of medulloblastoma growth in vitro and in vivo.
abstract: BACKGROUND
  Medulloblastoma is the most common brain tumor in children, and its prognosis is worse than for many other common pediatric cancers. Survivors undergoing treatment suffer from serious therapy-related side effects. Thus, it is imperative to identify safer, effective treatments for medulloblastoma. In this study we evaluated the anti-cancer potential of curcumin in medulloblastoma by testing its ability to induce apoptosis and inhibit tumor growth in vitro and in vivo using established medulloblastoma models.
  
  
  METHODS
  Using cultured medulloblastoma cells, tumor xenografts, and the Smo/Smo transgenic medulloblastoma mouse model, the antitumor effects of curcumin were tested in vitro and in vivo.
  
  
  RESULTS
  Curcumin induced apoptosis and cell cycle arrest at the G2/M phase in medulloblastoma cells. These effects were accompanied by reduced histone deacetylase (HDAC) 4 expression and activity and increased tubulin acetylation, ultimately leading to mitotic catastrophe. In in vivo medulloblastoma xenografts, curcumin reduced tumor growth and significantly increased survival in the Smo/Smo transgenic medulloblastoma mouse model.
  
  
  CONCLUSIONS
  The in vitro and in vivo data suggest that curcumin has the potential to be developed as a therapeutic agent for medulloblastoma.
authors.affiliation: Nemours Center for Childhood Cancer Research, Alfred I, duPont Hospital for Children, 1701 Rockland Road, Wilmington, DE 19803, USA.
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Lee
authors.forename: Candice
authors.initials: C
authors.lastname: Krauthauser
authors.forename: Victoria
authors.initials: V
authors.lastname: Maduskuie
authors.forename: Paul T
authors.initials: PT
authors.lastname: Fawcett
authors.forename: James M
authors.initials: JM
authors.lastname: Olson
authors.forename: Sigrid A
authors.initials: SA
authors.lastname: Rajasekaran
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D048708:Cell Growth Processes / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002528:Cerebellar Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008527:Medulloblastoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D000072086:Smoothened Receptor; D014404:Tubulin / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D043562:Receptors, G-Protein-Coupled; D012097:Repressor Proteins; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D014404:Tubulin; C400300:HDAC4 protein, human; D006655:Histone Deacetylases; D003474:Curcumin