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Valproic acid suppresses the self-renewal and proliferation of head and neck cancer stem cells. Oncol Rep 2015 Oct;34(4):2065-71

Date

08/05/2015

Pubmed ID

26239260

DOI

10.3892/or.2015.4145

Scopus ID

2-s2.0-84939160349   6 Citations

Abstract

Emerging evidence suggests that cancer cells present profound epigenetic alterations in addition to featuring classic genetic mutations. Valproic acid (VPA), a histone deacetylase inhibitor, can potently inhibit tumor growth and induce differentiation. However, the effect and underlying mechanism of VPA on head and neck squamous cell carcinoma (HNSCC) cancer stem cells (CSCs) remain unclear. In the present study we investigated the effects of VPA on the characteristics of HNSCC CSCs in vitro and in vivo. As a result, VPA inhibited the self-renewal abilities of HNSCC CSCs during two serial passages and decreased the expression of stem cell markers, such as Oct4, Sox2 and CD44. VPA also potentiated the cytotoxic effect of cisplatin by suppressing the ABCC2 and ABCC6 transporters as well as by inducing caspase-mediated apoptosis. In addition, the combination of VPA and cisplatin attenuated tumor growth and induced apoptosis in a xenograft model. Our results suggest that VPA might be a potential therapeutic strategy in combination with conventional cisplatin for HNSCC patients by elimination of CSC traits.

Author List

Lee SH, Nam HJ, Kang HJ, Samuels TL, Johnston N, Lim YC

Author

Nikki Johnston PhD Associate Professor in the Otolaryngology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antineoplastic Agents
Antineoplastic Combined Chemotherapy Protocols
Cell Line, Tumor
Cell Proliferation
Cell Self Renewal
Cisplatin
Drug Synergism
Gene Expression Regulation, Neoplastic
Head and Neck Neoplasms
Humans
Hyaluronan Receptors
Mice
Neoplastic Stem Cells
Octamer Transcription Factor-3
SOXB1 Transcription Factors
Valproic Acid
Xenograft Model Antitumor Assays
jenkins-FCD Prod-480 9a4deaf152b0b06dd18151814fff2e18f6c05280