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Tumor Biology

, Volume 36, Issue 7, pp 5051–5061 | Cite as

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

  • Bohan Yang
  • Dandan Yu
  • Jingwen Liu
  • Kunyu Yang
  • Gang Wu
  • Hongli Liu
Research Article

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.

Keywords

Suberoylanilide hydroxamic acid Histone deacetylase inhibitor Murine B cell lymphoma Antitumor activity 

Notes

Acknowledgments

Thanks are expressed to the Laboratory of Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, and for the laboratory of Electron Microscopy of Tongji Medical College for offering relevant experimental facilities and technical support.

This work was supported by the Science Foundation of Hubei Health Department (No. JX6B08), Wujieping Medical Foundation (No.320.6750.13277), and National Nature Science Foundation of China (No. 81472707).

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Bohan Yang
    • 1
  • Dandan Yu
    • 1
  • Jingwen Liu
    • 1
  • Kunyu Yang
    • 1
  • Gang Wu
    • 1
  • Hongli Liu
    • 1
  1. 1.Cancer Center, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

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