Suberoylanilide hydroxamic acid (SAHA) has potent anti-glioma properties in vitro, ex vivo and in vivo

J Neurochem. 2005 May;93(4):992-9. doi: 10.1111/j.1471-4159.2005.03098.x.


Current treatment modalities for malignant gliomas do not allow long-term survival. Here, we identify suberoylanilide hydroxamic acid (SAHA), an inhibitor of histone deacetylases (HDAC), as an effective experimental anti-glioma agent. Administration of SAHA to various glioma cell lines obtained from human, rat and mouse inhibited tumour cell growth in a range of 1-10 microm. This anti-glioma property is associated with up-regulation of the cell cycle control protein p21/WAF, as well as the induction of apoptosis. A novel tumour invasion model using slice cultures of rat brain corroborated the anti-glioma properties of SAHA in the organotypic brain environment. In this model, glioma invasion compromised adjacent brain parenchyma, and this tumour-associated cytotoxicity could be inhibited by SAHA. In addition, a 10-fold dose escalation experiment did not challenge the viability of cultured brain slices. In vivo, a single intratumoural injection of SAHA 7 days after orthotopic implantation of glioma cells in syngeneic rats doubled their survival time. These observations identify chromatin-modifying enzymes as possible and promising targets for the pharmacotherapy of malignant gliomas.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Animals
  • Animals, Newborn
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Benzamides / therapeutic use
  • Blotting, Western / methods
  • Cell Cycle Proteins / metabolism
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p21
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Flow Cytometry / methods
  • Glioma / drug therapy*
  • Glioma / metabolism
  • Glioma / pathology
  • Histone Deacetylase Inhibitors
  • Histones / metabolism
  • Humans
  • Hydroxamic Acids / therapeutic use*
  • Mice
  • Neoplasm Transplantation / methods
  • Organ Culture Techniques
  • Peptides, Cyclic / therapeutic use
  • Rats
  • Rats, Inbred F344
  • Rats, Wistar
  • Tetrazolium Salts
  • Thiazoles
  • Time Factors
  • Vorinostat


  • Antineoplastic Agents
  • Benzamides
  • CDKN1A protein, human
  • Cdkn1a protein, mouse
  • Cdkn1a protein, rat
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Histone Deacetylase Inhibitors
  • Histones
  • Hydroxamic Acids
  • Peptides, Cyclic
  • Tetrazolium Salts
  • Thiazoles
  • apicidin
  • Vorinostat
  • thiazolyl blue