Anti-tumor effects of suberoylanilide hydroxamic acid on Epstein-Barr virus-associated T cell and natural killer cell lymphoma

Mohammed N.A. Siddiquey, Hikaru Nakagawa, Seiko Iwata, Tetsuhiro Kanazawa, Michio Suzuki, Ken Ichi Imadome, Shigeyoshi Fujiwara, Fumi Goshima, Takayuki Murata, Hiroshi Kimura

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Abstract

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. SAHA inhibits tumor growth and metastasis of EBV-positive NK cell lymphoma. EBER-positive cells were detected by in situ hybridization in organ tissues of SAHA-treated or control mice.

Original languageEnglish
Pages (from-to)713-722
Number of pages10
JournalCancer Science
Volume105
Issue number6
DOIs
Publication statusPublished - 01-01-2014

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Human Herpesvirus 4
Natural Killer Cells
Lymphoma
T-Lymphocytes
Neoplasms
Cell Line
Natural Killer T-Cells
Histone Deacetylase Inhibitors
Cell Cycle Checkpoints
vorinostat
Apoptosis
Neoplasm Metastasis
Heterografts
In Situ Hybridization
B-Lymphocytes
Gene Expression

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Siddiquey, M. N. A., Nakagawa, H., Iwata, S., Kanazawa, T., Suzuki, M., Imadome, K. I., ... Kimura, H. (2014). Anti-tumor effects of suberoylanilide hydroxamic acid on Epstein-Barr virus-associated T cell and natural killer cell lymphoma. Cancer Science, 105(6), 713-722. https://doi.org/10.1111/cas.12418
Siddiquey, Mohammed N.A. ; Nakagawa, Hikaru ; Iwata, Seiko ; Kanazawa, Tetsuhiro ; Suzuki, Michio ; Imadome, Ken Ichi ; Fujiwara, Shigeyoshi ; Goshima, Fumi ; Murata, Takayuki ; Kimura, Hiroshi. / Anti-tumor effects of suberoylanilide hydroxamic acid on Epstein-Barr virus-associated T cell and natural killer cell lymphoma. In: Cancer Science. 2014 ; Vol. 105, No. 6. pp. 713-722.
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Siddiquey, MNA, Nakagawa, H, Iwata, S, Kanazawa, T, Suzuki, M, Imadome, KI, Fujiwara, S, Goshima, F, Murata, T & Kimura, H 2014, 'Anti-tumor effects of suberoylanilide hydroxamic acid on Epstein-Barr virus-associated T cell and natural killer cell lymphoma', Cancer Science, vol. 105, no. 6, pp. 713-722. https://doi.org/10.1111/cas.12418

Anti-tumor effects of suberoylanilide hydroxamic acid on Epstein-Barr virus-associated T cell and natural killer cell lymphoma. / Siddiquey, Mohammed N.A.; Nakagawa, Hikaru; Iwata, Seiko; Kanazawa, Tetsuhiro; Suzuki, Michio; Imadome, Ken Ichi; Fujiwara, Shigeyoshi; Goshima, Fumi; Murata, Takayuki; Kimura, Hiroshi.

In: Cancer Science, Vol. 105, No. 6, 01.01.2014, p. 713-722.

Research output: Contribution to journalArticle

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T1 - Anti-tumor effects of suberoylanilide hydroxamic acid on Epstein-Barr virus-associated T cell and natural killer cell lymphoma

AU - Siddiquey, Mohammed N.A.

AU - Nakagawa, Hikaru

AU - Iwata, Seiko

AU - Kanazawa, Tetsuhiro

AU - Suzuki, Michio

AU - Imadome, Ken Ichi

AU - Fujiwara, Shigeyoshi

AU - Goshima, Fumi

AU - Murata, Takayuki

AU - Kimura, Hiroshi

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N2 - 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. SAHA inhibits tumor growth and metastasis of EBV-positive NK cell lymphoma. EBER-positive cells were detected by in situ hybridization in organ tissues of SAHA-treated or control mice.

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