Journal
ONCOLOGY REPORTS
Volume 34, Issue 4, Pages 2065-2071Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2015.4145
Keywords
head and neck cancer; cancer stem cells; valproic acid; epigenetic regulation; therapy
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Funding
- National Research Foundation of Korea (NRF) - Korea government (MEST) [2011-0014237, 2012R1A2A2A01046214]
- National Research Foundation of Korea [2011-0014237, 2012R1A2A2A01046214] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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.
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