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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.

Author information

Choo DW1, Goh SH2, Cho YW1,3, Baek HJ1, Park EJ4, Motoyama N5,6, Kim TH1, Kim JY1, Kim SS1.

1Radiation Medicine Branch, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea.2Cancer Genomics Branch, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea.3Colgate University, Hamilton, NY 13346, USA.4Cancer Immunology Branch, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea.5Department of Cognitive Brain Science, National Centre for Geriatrics and Gerontology, Obu, Aichi 474-8522, Japan.6Department of Aging Research, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.