Manipulating histone acetylation leads to antitumor effects in hemangiosarcoma cells

Area of Science:

• Oncology
• Epigenetics
• Veterinary Medicine

Background:

• Canine hemangiosarcoma (HSA) is a deadly cancer with unknown pathogenesis.
• Epigenetic modifications like histone acetylation are crucial in cancer development.
• Histone deacetylase inhibitors (HDACi) and bromodomain and extraterminal domain inhibitors (BETi) are potential cancer treatments.

Purpose of the Study:

• To investigate the role of histone acetylation in canine hemangiosarcoma.
• To evaluate the efficacy of HDACi (SAHA, VPA) and a BETi (JQ1) in canine hemangiosarcoma models.

Main Methods:

• In vitro studies using HSA cell lines.
• In vivo studies using mouse models.
• Assessment of apoptosis, cell cycle, autophagy, and gene expression.
• Evaluation of immune cell recruitment.

Main Results:

• Histone acetylation levels were high in HSA cell lines and varied in clinical samples.
• SAHA and JQ1 induced apoptosis in HSA cells.
• SAHA and VPA modulated inflammatory gene expression and attracted macrophages.
• JQ1 promoted autophagy and cell cycle arrest in HSA cells.
• JQ1 inhibited HSA tumor growth in vivo, while SAHA and VPA did not.

Conclusions:

• BET inhibitors represent a potential therapeutic strategy for canine hemangiosarcoma.
• Histone acetylation dysregulation is implicated in HSA malignancy.
• Further research is warranted to explore BETi for HSA treatment.