Curcumin-induced HDAC inhibition and attenuation of medulloblastoma growth in vitro and in vivo

BMC Cancer. 2011 Apr 18:11:144. doi: 10.1186/1471-2407-11-144.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Growth Processes / drug effects
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Cerebellar Neoplasms / drug therapy*
  • Cerebellar Neoplasms / genetics
  • Cerebellar Neoplasms / pathology
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Medulloblastoma / drug therapy*
  • Medulloblastoma / genetics
  • Medulloblastoma / pathology
  • Mice
  • Mice, Transgenic
  • Receptors, G-Protein-Coupled / genetics
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Smoothened Receptor
  • Tubulin / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Receptors, G-Protein-Coupled
  • Repressor Proteins
  • Smo protein, mouse
  • Smoothened Receptor
  • Tubulin
  • HDAC4 protein, human
  • Histone Deacetylases
  • Curcumin