Antitumour effect of valproic acid against salivary gland cancer in vitro and in vivo

Hirokazu Nagai, Masako Fujioka-Kobayashi, G. O. Ohe, Kanae Hara, Natsumi Takamaru, Daisuke Uchida, Tetsuya Tamatani, Kenji Fujisawa, Youji Miyamoto

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Salivary gland cancer (SGC) has a comparatively poor prognosis and is prone to frequent recurrence and metastases. Therefore, the development of more effective chemotherapy against SGC is desirable. The aim of the present study was to investigate the antitumour effects of valproic acid (VPA) against SGC in vitro and in vivo. Two human SGC cell lines (HSY and HSG cells) were used in the present study. The effects of VPA on the proliferation of SGC cells in vitro were assessed by MTT assay. Cancer cells treated with VPA were subjected to cell cycle analysis by flow cytometry. In addition, the expression levels of p21 and p27 were examined by real-time RT-PCR to identify the mechanisms of the antitumour effect of VPA on SGC. The effects of VPA on cancer growth in vivo were evaluated in a xenograft model. VPA inhibited the proliferation of SGC cells in a dose-dependent manner in vitro. Degenerated cancer cells were observed at high concentrations of VPA. In the cell cycle analysis, VPA induced cell-growth inhibition and G1 arrest of cell cycle progression in both cancer cell lines in a time-and dose-dependent manner. VPA markedly upregulated the mRNA expression levels of both p21 and p27 in both SGC cell lines in a time-dependent manner. In the xenograft model experiment, VPA treatment markedly inhibited the growth of salivary gland tumours when compared with the growth of the untreated controls. VPA may be a valuable drug in the development of better therapeutic regimens for SGC.

Original languageEnglish
Pages (from-to)1453-1458
Number of pages6
JournalOncology reports
Volume31
Issue number3
DOIs
Publication statusPublished - 2014 Mar 1
Externally publishedYes

Keywords

  • Antitumour activity
  • Epigenetics
  • Histone deacetylase inhibitor
  • Salivary gland cancer
  • Valproic acid

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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