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 journalArticle

2 Citations (Scopus)

Abstract

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
JournalHematology
Volume17
Issue number3
DOIs
Publication statusPublished - May 2012

Fingerprint

Valproic Acid
Human Herpesvirus 4
Natural Killer Cells
Lymphoproliferative Disorders
Viruses
Cyclin D2
G1 Phase Cell Cycle Checkpoints
Cyclin E
Histone Deacetylase Inhibitors
Caspase 8
Caspase 3
Histones
Cell Line
Therapeutics
Growth

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

Fujii, K., Suzuki, N., Yamamoto, T., Suzuki, D., & Iwatsuki, K. (2012). Valproic acid inhibits proliferation of EB virus-infected natural killer cells. Hematology, 17(3), 163-169. https://doi.org/10.1179/102453312X13376952196494

Valproic acid inhibits proliferation of EB virus-infected natural killer cells. / Fujii, Kazuyasu; Suzuki, Norihiro; Yamamoto, Takenobu; Suzuki, Daisuke; Iwatsuki, Keiji.

In: Hematology, Vol. 17, No. 3, 05.2012, p. 163-169.

Research output: Contribution to journalArticle

Fujii, K, Suzuki, N, Yamamoto, T, Suzuki, D & Iwatsuki, K 2012, 'Valproic acid inhibits proliferation of EB virus-infected natural killer cells', Hematology, vol. 17, no. 3, pp. 163-169. https://doi.org/10.1179/102453312X13376952196494
Fujii, Kazuyasu ; Suzuki, Norihiro ; Yamamoto, Takenobu ; Suzuki, Daisuke ; Iwatsuki, Keiji. / Valproic acid inhibits proliferation of EB virus-infected natural killer cells. In: Hematology. 2012 ; Vol. 17, No. 3. pp. 163-169.
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