Anti-tumor effects of suberoylanilide hydroxamic acid on Epstein–Barr virus-associated T cell and natural killer cell lymphoma
Version of Record online: 12 MAY 2014
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Volume 105, Issue 6, pages 713–722, June 2014
How to Cite
Cancer Sci 105 (2014) 713–722
Ministry of Education, Culture, Sports, Science and Technology of Japan (25293109). Ministry of Health, Labour and Welfare of Japan (H24-Nanchi-046).
- Issue online: 4 JUN 2014
- Version of Record online: 12 MAY 2014
- Accepted manuscript online: 8 APR 2014 12:01PM EST
- Manuscript Accepted: 7 APR 2014
- Manuscript Revised: 31 MAR 2014
- Manuscript Received: 26 FEB 2014
- Ministry of Education, Culture, Sports, Science and Technology of Japan. Grant Number: 25293109
- Ministry of Health, Labour and Welfare of Japan. Grant Number: H24-Nanchi-046
- Extranodal NK-T-cell lymphoma;
- histone deacetylase inhibitor;
- human herpesvirus 4;
- hydroxamic acid;
- SCID mice
The ubiquitous Epstein–Barr virus (EBV) infects not only B cells but also T cells and natural killer (NK) cells and is associated with various lymphoid malignancies. Recent studies have reported that histone deacetylase (HDAC) inhibitors exert anticancer effects against various tumor cells. In the present study, we have evaluated both the in vitro and in vivo effects of suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor, on EBV-positive and EBV-negative T and NK lymphoma cells. Several EBV-positive and EBV-negative T and NK cell lines were treated with various concentrations of SAHA. SAHA suppressed the proliferation of T and NK cell lines, although no significant difference was observed between EBV-positive and EBV-negative cell lines. SAHA induced apoptosis and/or cell cycle arrest in several T and NK cell lines. In addition, SAHA increased the expression of EBV-lytic genes and decreased the expression of EBV-latent genes. Next, EBV-positive NK cell lymphoma cells were subcutaneously inoculated into severely immunodeficient NOD/Shi-scid/IL-2Rγnull mice, and then SAHA was administered intraperitoneally. SAHA inhibited tumor progression and metastasis in the murine xenograft model. SAHA displayed a marked suppressive effect against EBV-associated T and NK cell lymphomas through either induction of apoptosis or cell cycle arrest, and may represent an alternative treatment option.