Anti-tumor effects of suberoylanilide hydroxamic acid on Epstein-Barr virus-associated T cell and natural killer cell lymphoma.
Bottom Line: SAHA suppressed the proliferation of T and NK cell lines, although no significant difference was observed between EBV-positive and EBV-negative cell lines.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: The expression of eight EBV-related genes, including lytic genes (BZLF1 and gp350/220) and latent genes (EBNA1, EBNA2, LMP1, LMP2, EBER1 and Bam HI-A rightward transcripts [BART]) were analyzed using real-time RT-PCR. In the SNT13, KAI3 and SNK6 cell lines, the expression of BZLF1, which is an immediate-early gene in the lytic infection cycle, was increased by SAHA (Fig.5). However, the expression of the late lytic gene gp350/220 was increased only in the SAHA-treated SNT13 cell line. These results indicated that SAHA induced lytic infection in some EBV-positive T and NK cell lines, although it was abortive. The expression of BZLF1 was decreased in the SAHA-treated SNT16 as time went by, while that in mock-treated SNT16 was also decreased. Of the EBV latent genes tested, the expression of EBNA1, LMP1 and BART was decreased in most of the cell lines, whereas that of LMP2 was increased by SAHA (Fig.5). Next, the EBNA1 and LMP1 protein levels were determined by immunoblotting. SAHA decreased the EBNA1 protein level in all cell lines, and that of LMP1 in the SNT16, KAI3 and SNK6 cell lines (Fig.6).
Affiliation: Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan.