A quinazoline-based HDAC inhibitor affects gene expression pathways involved in cholesterol biosynthesis and mevalonate in prostate cancer cells

Mol Biosyst. 2016 Mar;12(3):839-49. doi: 10.1039/c5mb00554j.

Abstract

Chronic inflammation can lead to the development of cancers and resolution of inflammation is an ongoing challenge. Inflammation can result from dysregulation of the epigenome and a number of compounds that modify the epigenome are in clinical use. In this study the anti-inflammatory and anti-cancer effects of a quinazoline epigenetic-modulator compound were determined in prostate cancer cell lines using a non-hypothesis driven transcriptomics strategy utilising the Affymetrix PrimeView® Human Gene Expression microarray. GATHER and IPA software were used to analyse the data and to provide information on significantly modified biological processes, pathways and networks. A number of genes were differentially expressed in both PC3 and DU145 prostate cancer cell lines. The top canonical pathways that frequently arose across both cell lines at a number of time points included cholesterol biosynthesis and metabolism, and the mevalonate pathway. Targeting of sterol and mevalonate pathways may be a powerful anticancer approach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cholesterol / biosynthesis*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Male
  • Mevalonic Acid / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Prostatic Neoplasms / genetics*
  • Quinazolines / pharmacology*
  • Reproducibility of Results
  • Signal Transduction / drug effects
  • Signal Transduction / genetics

Substances

  • Histone Deacetylase Inhibitors
  • Quinazolines
  • Cholesterol
  • Mevalonic Acid