Open Access

CHK2 is involved in the p53-independent radiosensitizing effects of valproic acid

  • Authors:
    • Dong Wan Choo
    • Sung Ho Goh
    • Young Woo Cho
    • Hye Jung Baek
    • Eun Jung Park
    • Noboru Motoyama
    • Tae Hyun Kim
    • Joo Young Kim
    • Sang Soo Kim
  • View Affiliations

  • Published online on: March 1, 2017     https://doi.org/10.3892/ol.2017.5792
  • Pages: 2591-2598
  • Copyright: © Choo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Radiotherapy is an effective treatment for the majority of types of localized solid cancer. However, the risk of side effects to the surrounding normal tissues limits radiotherapeutic approaches. Whilst the mechanism of action of valproic acid, an inhibitor of histone deacetylase, remains unknown, the inhibitor is a potential antineoplastic radiosensitizer. The present study demonstrated the in vitro radiosensitizing effects of valproic acid on the human breast cancer MCF7 cell line, and revealed that valproic acid increased the level of DNA breakage, apoptosis and senescence. In addition, western blot analyses revealed that valproic acid induced tumor suppressor protein (p)53 and p21 expression, and activated checkpoint kinase 2 (CHK2) in MCF7 cells and primary mouse embryonic fibroblasts. Notably, treatment with valproic acid also induced increases in the level of p21 protein levels and CHK2 activity in p53‑null colon cancer HCT116 cells. Furthermore, the present study demonstrated that valproic acid‑induced radiosensitization was largely dependent on the activity of CHK2. The results of the present study reveal that valproic acid may exhibit clinical utility with respect to increasing the anticancer efficacy of radiotherapy by affecting the level of p53.

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April-2017
Volume 13 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Choo DW, Goh SH, Cho YW, Baek HJ, Park EJ, Motoyama N, Kim TH, Kim JY and Kim SS: CHK2 is involved in the p53-independent radiosensitizing effects of valproic acid. Oncol Lett 13: 2591-2598, 2017
APA
Choo, D.W., Goh, S.H., Cho, Y.W., Baek, H.J., Park, E.J., Motoyama, N. ... Kim, S.S. (2017). CHK2 is involved in the p53-independent radiosensitizing effects of valproic acid. Oncology Letters, 13, 2591-2598. https://doi.org/10.3892/ol.2017.5792
MLA
Choo, D. W., Goh, S. H., Cho, Y. W., Baek, H. J., Park, E. J., Motoyama, N., Kim, T. H., Kim, J. Y., Kim, S. S."CHK2 is involved in the p53-independent radiosensitizing effects of valproic acid". Oncology Letters 13.4 (2017): 2591-2598.
Chicago
Choo, D. W., Goh, S. H., Cho, Y. W., Baek, H. J., Park, E. J., Motoyama, N., Kim, T. H., Kim, J. Y., Kim, S. S."CHK2 is involved in the p53-independent radiosensitizing effects of valproic acid". Oncology Letters 13, no. 4 (2017): 2591-2598. https://doi.org/10.3892/ol.2017.5792