Valproic acid suppresses the self-renewal and proliferation of head and neck cancer stem cells

  • Authors:
    • Sang Hyuk Lee
    • Hyo Jung Nam
    • Hyun Jung Kang
    • Tina L. Samuels
    • Nikki Johnston
    • Young Chang Lim
  • View Affiliations

  • Published online on: July 23, 2015     https://doi.org/10.3892/or.2015.4145
  • Pages: 2065-2071
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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.
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October-2015
Volume 34 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Lee SH, Nam HJ, Kang HJ, Samuels TL, Johnston N and Lim YC: Valproic acid suppresses the self-renewal and proliferation of head and neck cancer stem cells. Oncol Rep 34: 2065-2071, 2015.
APA
Lee, S.H., Nam, H.J., Kang, H.J., Samuels, T.L., Johnston, N., & Lim, Y.C. (2015). Valproic acid suppresses the self-renewal and proliferation of head and neck cancer stem cells. Oncology Reports, 34, 2065-2071. https://doi.org/10.3892/or.2015.4145
MLA
Lee, S. H., Nam, H. J., Kang, H. J., Samuels, T. L., Johnston, N., Lim, Y. C."Valproic acid suppresses the self-renewal and proliferation of head and neck cancer stem cells". Oncology Reports 34.4 (2015): 2065-2071.
Chicago
Lee, S. H., Nam, H. J., Kang, H. J., Samuels, T. L., Johnston, N., Lim, Y. C."Valproic acid suppresses the self-renewal and proliferation of head and neck cancer stem cells". Oncology Reports 34, no. 4 (2015): 2065-2071. https://doi.org/10.3892/or.2015.4145