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Ref Type Journal Article
PMID (26135807)
Authors Makita N, Ninomiya I, Tsukada T, Okamoto K, Harada S, Nakanuma S, Sakai S, Makino I, Kinoshita J, Hayashi H, Oyama K, Nakagawara H, Miyashita T, Tajima H, Takamura H, Fushida S, Ohta T
Title Inhibitory effects of valproic acid in DNA double-strand break repair after irradiation in esophageal squamous carcinoma cells.
Journal Vol Issue Date Pages Journal Short Title
Oncology reports 34 3 2015 Sep 1185-92 Oncol Rep
URL
Abstract Text Radiation therapy is one of the most promising therapeutic strategies in unresectable esophageal squamous cell carcinoma (ESCC). The histone deacetylase (HDAC) inhibitor has been shown to enhance radiosensitivity. Valproic acid (VPA) is a well-known drug used to treat seizure disorders and epilepsy, and has been shown to inhibit HDACs. We recently reported that a clinically safe dose of VPA enhances radiation‑induced cytotoxicity in human ESCC cells. However, the mechanism of radiosensitizing effect of VPA has not yet been confirmed. The present study examined the effect of VPA on DNA double-strand break (DSB) repair after radiation in the human ESCC cell lines KES, TE9 and TE11 by examining H2AX phosphorylation (γH2AX) levels as a marker of radiation‑induced DSBs. The present study also examined whether VPA inhibited radiation-induced DNA DSB repair by suppressing non-homologous end joining (NHEJ), focusing particularly on the acetylation of Ku70. VPA was shown to prolong γH2AX levels after irradiation in all three ESCC cell lines. Moreover, prolonged γH2AX foci formation after irradiation was also observed by immunocytochemistry following VPA pretreatment in KES and TE9 cells. VPA was shown to induce Ku70 acetylation after irradiation in all three ESCC cell lines. Our results suggest that VPA prolonged radiation‑induced DSBs by inhibiting NHEJ in DSB repair pathways in ESCC. VPA could therefore be used as an effective radiosensitizer in ESCC radiotherapy.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References