Valproic acid inhibits proliferation of EB virus-infected natural killer cells

Kazuyasu Fujii, Norihiro Suzuki, Takenobu Yamamoto, Daisuke Suzuki, Keiji Iwatsuki

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


There is no recognized treatment for Epstein-Barr virus (EBV)-associated natural killer (NK) cell lymphoproliferative disorders (LPDs). To determine the possibility of histone deacetylase inhibitors as a therapeutic tool for such disorders, we investigated the anti-proliferative effects of valproic acid (VPA) on two EBV-infected NK cell lines (KAI3 and NKED). VPA inhibited the growth of both lines in a dose- and time-dependent manner by inducing histone hyperacetylation. G1 cell cycle arrest was induced at 24 hours and was associated with increased expression of p21WAF1, p27Kip1, and cyclin E and decreased expression of cyclin D2, CDK4, and c-myc. Sub-G1 fractions were not significantly changed at 24 hours, whereas cleaved caspase-3 and cleaved PARP were already detected, and the extrinsic apoptotic pathway, determined by cleaved caspase-8, was activated. Finally, sub-G1 accumulation was increased after 72 hours following stimulation. These findings indicate that VPA might be a therapeutic option for EBV-associated NK-cell LPDs.

Original languageEnglish
Pages (from-to)163-169
Number of pages7
Issue number3
Publication statusPublished - May 2012


  • Epstein-Barr virus
  • HDAC inhibitor
  • NK cell
  • P21WAF1
  • Valproic acid

ASJC Scopus subject areas

  • Hematology


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