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 language | English |
|---|---|
| Pages (from-to) | 163-169 |
| Number of pages | 7 |
| Journal | Hematology |
| Volume | 17 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - May 2012 |
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Keywords
- Epstein-Barr virus
- HDAC inhibitor
- NK cell
- P21WAF1
- Valproic acid
ASJC Scopus subject areas
- Hematology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Valproic acid inhibits proliferation of EB virus-infected natural killer cells
AU - Fujii, Kazuyasu
AU - Suzuki, Norihiro
AU - Yamamoto, Takenobu
AU - Suzuki, Daisuke
AU - Iwatsuki, Keiji
PY - 2012/5
Y1 - 2012/5
N2 - 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.
AB - 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.
KW - Epstein-Barr virus
KW - HDAC inhibitor
KW - NK cell
KW - P21WAF1
KW - Valproic acid
UR - http://www.scopus.com/inward/record.url?scp=84863091199&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863091199&partnerID=8YFLogxK
U2 - 10.1179/102453312X13376952196494
DO - 10.1179/102453312X13376952196494
M3 - Article
C2 - 22664116
AN - SCOPUS:84863091199
VL - 17
SP - 163
EP - 169
JO - Hematology
JF - Hematology
SN - 1024-5340
IS - 3
ER -