Anti-tumor effects of suberoylanilide hydroxamic acid on Epstein-Barr virus-associated T cell and natural killer cell lymphoma.
Bottom Line: Recent studies have reported that histone deacetylase (HDAC) inhibitors exert anticancer effects against various tumor cells.In addition, SAHA increased the expression of EBV-lytic genes and decreased the expression of EBV-latent genes.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.
Affiliation: Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan.Show MeSH
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Mentions: Epstein–Barr virus-positive and EBV-negative T and NK cell lines were cultured with various concentrations of SAHA. SAHA increased acetylated histone H3 levels, confirming that SAHA worked as an HDAC inhibitor (Fig.1a). SAHA reduced the viability of all treated cell lines in a dose-dependent manner (Fig.1b). Next, the same six cell lines were treated with 5 μM SAHA and assessed at different time points. The viability of all six cell lines was reduced by treatment with SAHA for 96 h (Fig.1c). The effects of SAHA did not differ between EBV-positive and EBV-negative cell lines. In addition, to compare its effects on EBV-positive and EBV-negative cell lines, we treated MT2/rEBV/9-7 and MT2/rEBV/9-9 cells (EBV-positive T cell lines), MT2/hyg/CL2 and MT2/hyg/CL3 cells (EBV-negative T cell lines), TL1 cells (EBV-positive NK cell line) and NKL cells (EBV-negative parental NK cell line) with SAHA. SAHA had similar effects on the EBV-positive and EBV-negative cell lines (Fig.2a). Moreover, human PBMC were treated with SAHA to evaluate the adverse effects. Viability remained >69% at 96 h, indicating the absence of adverse effects (Fig.2b).
Affiliation: Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan.