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

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'd...

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Main Authors: Zain, R.B., Ismail, S.M., Wan Mustafa, W.M., Teo, S.H., Hor, S.Y., Hamid, S., Gan, C.P., Cheong, S.C., Saunders, N.
Format: Article
Language:English
Published: 2011
Subjects:
Online Access:http://eprints.um.edu.my/2359/1/Valproic_acid_Growth_inhibition_of_head_and_neck_cancer_by_induction_of_terminal_differentiation_and_senescence.pdf
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author Zain, R.B.
Ismail, S.M.
Wan Mustafa, W.M.
Teo, S.H.
Hor, S.Y.
Hamid, S.
Gan, C.P.
Cheong, S.C.
Saunders, N.
author_facet Zain, R.B.
Ismail, S.M.
Wan Mustafa, W.M.
Teo, S.H.
Hor, S.Y.
Hamid, S.
Gan, C.P.
Cheong, S.C.
Saunders, N.
author_sort Zain, R.B.
collection UM
description 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.
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spelling um.eprints-23592014-12-11T06:21:52Z http://eprints.um.edu.my/2359/ Valproic acid: Growth inhibition of head and neck cancer by induction of terminal differentiation and senescence Zain, R.B. Ismail, S.M. Wan Mustafa, W.M. Teo, S.H. Hor, S.Y. Hamid, S. Gan, C.P. Cheong, S.C. Saunders, N. RK Dentistry 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. 2011 Article PeerReviewed application/pdf en http://eprints.um.edu.my/2359/1/Valproic_acid_Growth_inhibition_of_head_and_neck_cancer_by_induction_of_terminal_differentiation_and_senescence.pdf Zain, R.B. and Ismail, S.M. and Wan Mustafa, W.M. and Teo, S.H. and Hor, S.Y. and Hamid, S. and Gan, C.P. and Cheong, S.C. and Saunders, N. (2011) Valproic acid: Growth inhibition of head and neck cancer by induction of terminal differentiation and senescence. Head and Neck. ISSN 1043-3074, DOI https://doi.org/10.1002/hed.21734 <https://doi.org/10.1002/hed.21734>. http://www.scopus.com/record/display.url?eid=2-s2.0-79953266064&origin=resultslist&sort=plfdt-f&listId=myList&src=s&imp=t&sid=qyRLrrzocIh_oYBXB6-cEq3%3a690&sot=ml&sdt=ml&sl=0&relpos=0&relpos=0&searchTerm= 10.1002/hed.21734
spellingShingle RK Dentistry
Zain, R.B.
Ismail, S.M.
Wan Mustafa, W.M.
Teo, S.H.
Hor, S.Y.
Hamid, S.
Gan, C.P.
Cheong, S.C.
Saunders, N.
Valproic acid: Growth inhibition of head and neck cancer by induction of terminal differentiation and senescence
title Valproic acid: Growth inhibition of head and neck cancer by induction of terminal differentiation and senescence
title_full Valproic acid: Growth inhibition of head and neck cancer by induction of terminal differentiation and senescence
title_fullStr Valproic acid: Growth inhibition of head and neck cancer by induction of terminal differentiation and senescence
title_full_unstemmed Valproic acid: Growth inhibition of head and neck cancer by induction of terminal differentiation and senescence
title_short Valproic acid: Growth inhibition of head and neck cancer by induction of terminal differentiation and senescence
title_sort valproic acid growth inhibition of head and neck cancer by induction of terminal differentiation and senescence
topic RK Dentistry
url http://eprints.um.edu.my/2359/1/Valproic_acid_Growth_inhibition_of_head_and_neck_cancer_by_induction_of_terminal_differentiation_and_senescence.pdf
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