Anti-tumour activity of Panobinostat in oesophageal adenocarcinoma and squamous cell carcinoma cell lines

Clin Epigenetics. 2024 Aug 3;16(1):102. doi: 10.1186/s13148-024-01700-3.

Abstract

Background: Oesophageal cancer remains a challenging disease with high mortality rates and few therapeutic options. In view of these difficulties, epigenetic drugs have emerged as potential alternatives for patient care. The goal of this study was to evaluate the effect and biological consequences of Panobinostat treatment, an HDAC (histone deacetylase) inhibitor already approved for treatment of patients with multiple myeloma, in oesophageal cell lines of normal and malignant origin, with the latter being representative of the two main histological subtypes: adenocarcinoma and squamous cell carcinoma.

Results: Panobinostat treatment inhibited growth and hindered proliferation, colony formation and invasion of oesophageal cancer cells. Considering HDAC tissue expression, HDAC1 was significantly upregulated in normal oesophageal epithelium in comparison with tumour tissue, whereas HDAC3 was overexpressed in oesophageal cancer compared to non-malignant mucosa. No differences between normal and tumour tissue were observed for HDAC2 and HDAC8 expression.

Conclusions: Panobinostat exposure effectively impaired malignant features of oesophageal cancer cells. Because HDAC3 was shown to be overexpressed in oesophageal tumour samples, this epigenetic drug may represent an alternative therapeutic option for oesophageal cancer patients.

Keywords: HDAC; Oesophageal cancer; Panobinostat.

MeSH terms

  • Adenocarcinoma* / drug therapy
  • Adenocarcinoma* / genetics
  • Adenocarcinoma* / pathology
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Squamous Cell* / drug therapy
  • Carcinoma, Squamous Cell* / genetics
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Epigenesis, Genetic / drug effects
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / genetics
  • Esophageal Neoplasms* / pathology
  • Esophageal Squamous Cell Carcinoma / drug therapy
  • Esophageal Squamous Cell Carcinoma / genetics
  • Esophageal Squamous Cell Carcinoma / pathology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Histone Deacetylase 1 / genetics
  • Histone Deacetylase 2 / genetics
  • Histone Deacetylase Inhibitors* / pharmacology
  • Histone Deacetylase Inhibitors* / therapeutic use
  • Histone Deacetylases* / genetics
  • Histone Deacetylases* / metabolism
  • Humans
  • Hydroxamic Acids / pharmacology
  • Hydroxamic Acids / therapeutic use
  • Indoles / pharmacology
  • Indoles / therapeutic use
  • Panobinostat* / administration & dosage
  • Panobinostat* / pharmacology
  • Panobinostat* / therapeutic use
  • Repressor Proteins / genetics

Substances

  • Panobinostat
  • Histone Deacetylases
  • Histone Deacetylase Inhibitors
  • Histone Deacetylase 1
  • HDAC1 protein, human
  • histone deacetylase 3
  • HDAC2 protein, human
  • Histone Deacetylase 2
  • HDAC8 protein, human
  • Repressor Proteins
  • Hydroxamic Acids
  • Antineoplastic Agents
  • Indoles

Supplementary concepts

  • Adenocarcinoma Of Esophagus