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Tumor Biology
Published in: Tumor Biology 7/2015

01-07-2015 | Research Article

Antitumor activity of SAHA, a novel histone deacetylase inhibitor, against murine B cell lymphoma A20 cells in vitro and in vivo

Authors: Bohan Yang, Dandan Yu, Jingwen Liu, Kunyu Yang, Gang Wu, Hongli Liu

Published in: Tumor Biology | Issue 7/2015

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Abstract

Suberoylanilide hydroxamic acid (SAHA; vorinostat), the second generation of histone deacetylase (HDAC) inhibitor, has been approved for the treatment of cutaneous manifestations of cutaneous T cell lymphoma (CTCL). It has also shown its anticancer activity over a large range of other hematological and solid malignancies, but few studies have been reported in B cell lymphoma. In this study, we aimed to investigate the antitumor activity of SAHA on murine B cell lymphoma cell line A20 cells. We treated A20 cells with different concentrations of SAHA. The effect of SAHA on the proliferation of A20 cells was studied by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) assay in vitro; the anti-proliferation activity in vivo was evaluated by proliferating cell nuclear antigen (PCNA) of xenograft tumor tissues through immunocytochemical staining. Apoptosis were detected by Hoechst 33258 staining and Annexin V/propidium iodide (PI) double-labeled cytometry in vitro. The effect of SAHA on cell cycle of A20 cells was studied by a propidium iodide method. Autophagic cell death induced by SAHA was confirmed by transmission electron microscopy (TEM). Angiogenesis marker (CD31) was measured by immunocytochemical staining to investigate the anti-angiogenic effect of SAHA. Western blot was used to detect the expression of signaling pathway factors (phospho-AKT, phospho-ERK, AKT, ERK, Nur77, HIF-1α, and VEGF). Our results showed that SAHA inhibited the proliferation of A20 cells in a time- and dose-dependent manner, induced cell apoptosis and G0/G1 phase arrest of cell cycle, promoted autophagic cell death, and suppressed tumor progress in NCI-A20 cells nude mice xenograft model in vivo. SAHA decreased the activation of AKT (phospho-AKT: p-AKT) and ERK1/2 (phospho-ERK: p-ERK) proteins and inhibited the expression of pro-angiogenic factors (VEGF and HIF-1α), downregulated its downstream signaling factor (Nur77), which might be contributed to the antitumor mechanisms of SAHA.
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Metadata
Title
Antitumor activity of SAHA, a novel histone deacetylase inhibitor, against murine B cell lymphoma A20 cells in vitro and in vivo
Authors
Bohan Yang
Dandan Yu
Jingwen Liu
Kunyu Yang
Gang Wu
Hongli Liu
Publication date
01-07-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 7/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3156-1

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