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Manipulating histone acetylation leads to antitumor effects in hemangiosarcoma cells

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Title: Manipulating histone acetylation leads to antitumor effects in hemangiosarcoma cells
Authors: Suzuki, Tamami Browse this author
Aoshima, Keisuke Browse this author
Yamazaki, Jumpei Browse this author
Kobayashi, Atsushi Browse this author
Kimura, Takashi Browse this author →KAKEN DB
Keywords: BETi
histone acetylation
Issue Date: 14-May-2022
Publisher: John Wiley & Sons
Journal Title: Veterinary and comparative oncology
Volume: 20
Issue: 4
Start Page: 805
End Page: 816
Publisher DOI: 10.1111/vco.12840
Abstract: Canine hemangiosarcoma (HSA) is a malignant tumour derived from endothelial cells. No effective treatment has yet been developed because of the lack of understanding of its pathogenesis. Histone acetylation, an epigenetic modification, is highly associated with cancer pathogenesis. Manipulating histone acetylation by histone deacetylase inhibitors (HDACi) or bromodomain and extraterminal domain inhibitors (BETi) is one approach to treat various cancers. However, the role of histone acetylation in HSA remains unknown. This study aimed to investigate how histone acetylation functions in HSA pathogenesis using two HDACi, suberanilohydroxamic acid (SAHA) and valproic acid (VPA), and one BETi, JQ1, in vitro and in vivo. Histone acetylation levels were high in cell lines and heterogeneous in clinical cases. SAHA and JQ1 induced apoptosis in HSA cell lines. HSA cell lines treated with SAHA and VPA upregulated inflammatory-related genes and attracted macrophage cell line RAW264 cells, which suggests that SAHA and VPA can affect immune responses. JQ1 stimulated autophagy and inhibited the cell cycle in HSA cell lines. Finally, we demonstrated that JQ1 suppressed HSA tumour cell proliferation in vivo although SAHA and VPA did not affect tumour growth. These results suggest that BETi can be alternative drugs for HSA treatment. Although further research is required, our study indicated that dysregulation of histone acetylation is likely to be involved in HSA malignancy.
Rights: This is the peer reviewed version of the following article: SUZUKI, Tamami, et al. Manipulating Histone Acetylation Leads to Antitumor Effects in Hemangiosarcoma Cells. Veterinary and Comparative Oncology, 2022., which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
Type: article (author version)
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 青島 圭佑

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