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Valproic acid: Growth inhibition of head and neck cancer by induction of terminal differentiation and senescence
Author(s) -
Gan Chai Phei,
Hamid Sharifah,
Hor Seen Yii,
Zain Rosnah Binti,
Ismail Siti Mazlipah,
Wan Mustafa Wan Mahadzir,
Teo Soo Hwang,
Saunders Nicholas,
Cheong Sok Ching
Publication year - 2012
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.21734
Subject(s) - clonogenic assay , head and neck squamous cell carcinoma , retinoic acid , valproic acid , cancer research , cell growth , growth inhibition , cell culture , downregulation and upregulation , senescence , epigenetics , chemistry , biology , cancer , head and neck cancer , microbiology and biotechnology , biochemistry , genetics , neuroscience , gene , epilepsy
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. © 2011 Wiley Periodicals, Inc. Head Neck, 2012