title: Valproic acid: growth inhibition of head and neck cancer by induction of terminal differentiation and senescence.
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.
  
  
  CONCLUSIONS
  VPA is a potent inhibitor of proliferation in some HNSCC cell lines, and may be used to treat HNSCC.
authors: Oral Cancer Research Team, Cancer Research Initiatives Foundation, Second Floor, Outpatient Centre, Sime Darby Medical Centre, 47500 Subang Jaya, Selangor, Malaysia.
authors: Chai Phei
authors: CP
authors: Gan
authors: Sharifah
authors: S
authors: Hamid
authors: Seen Yii
authors: SY
authors: Hor
authors: Rosnah Binti
authors: RB
authors: Zain
authors: Siti Mazlipah
authors: SM
authors: Ismail
authors: Wan Mahadzir
authors: WM
authors: Wan Mustafa
authors: Soo Hwang
authors: SH
authors: Teo
authors: Nicholas
authors: N
authors: Saunders
authors: Sok Ching
authors: SC
authors: Cheong
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D016922:Cellular Senescence / Q000187:drug effects*; D000077209:Decitabine; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D000077195:Squamous Cell Carcinoma of Head and Neck; D014212:Tretinoin / Q000494:pharmacology / Q000627:therapeutic use; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D014212:Tretinoin; D014635:Valproic Acid; D000077209:Decitabine; D001374:Azacitidine