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Gan, C. P. and Hamid, S. and Hor, S. Y. and Zain, R. B. and Ismail, S. M. and Mustafa, W. M. W. and Teo, S. H. and Saunders, N. and Cheong, S. C. (2011) Valproic acid: Growth inhibition of head and neck cancer by induction of terminal differentiation and senescence. Head and Neck. ISSN 1043-3074

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    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.

    Item Type: Article
    Uncontrolled Keywords: Histone Deacetylase Inhibitor; Valproic Acid; Head and Neck Cancer; Terminal Differentiation; Senescence
    Subjects: Medicine and Dentistry
    Divisions: UNSPECIFIED
    Depositing User: Prof. Dr. Rosnah Mohd Zain
    Date Deposited: 09 Feb 2012 01:46
    Last Modified: 09 Feb 2012 01:46
    URI: http://opendepot.org/id/eprint/685

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