Valproic acid: growth inhibition of head and neck cancer by induction of terminal differentiation and senescence

Head Neck. 2012 Mar;34(3):344-53. doi: 10.1002/hed.21734. Epub 2011 Mar 24.

Abstract

Background: There are limited studies on the effects of drugs that modulate epigenetic regulation for head and neck squamous cell carcinoma (HNSCC). This study determined the effect of valproic acid (VPA) on HNSCC.

Methods: Growth inhibition effects of VPA alone or in combination with 5-aza-2'deoxycytidine (5-aza-dC) or all-trans retinoic acid (ATRA) was evaluated with MTT and clonogenic assays on 5 HNSCC cell lines. The mechanism of growth inhibition was investigated by looking at markers of terminal differentiation and senescence.

Results: Growth inhibition profiles of HNSCC cell lines varied in response to VPA. Inhibition of clonogenic survival in response to VPA was associated with an upregulation of p21, expression of terminal differentiation markers, and cellular senescence. Notably, a combination treatment of 5-Aza-dC-VPA-ATRA enhanced growth inhibition in cells resistant to VPA.

Conclusion: VPA is a potent inhibitor of proliferation in some HNSCC cell lines, and may be used to treat HNSCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Azacitidine / therapeutic use
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / pathology*
  • Cell Culture Techniques
  • Cell Differentiation / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cellular Senescence / drug effects*
  • Decitabine
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / pathology*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Squamous Cell Carcinoma of Head and Neck
  • Tretinoin / pharmacology
  • Tretinoin / therapeutic use
  • Valproic Acid / pharmacology*

Substances

  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • Tretinoin
  • Valproic Acid
  • Decitabine
  • Azacitidine