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Updated: Mar 27, 2026

Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
A quinazoline-based HDAC inhibitor affects gene expression pathways involved in cholesterol biosynthesis and
Z Lin1, K S Bishop1, H Sutherland1
1Auckland Cancer Society Research Centre, University of Auckland, New Zealand. k.bishop@auckland.ac.nz.
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.
Insights
This study investigated a quinazoline epigenetic modulator for its anti-inflammatory and anti-cancer effects in prostate cancer. The compound impacted cholesterol and mevalonate pathways, suggesting a potential therapeutic strategy.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Chronic inflammation is linked to cancer development, presenting a significant clinical challenge.
- Epigenetic dysregulation is a key factor in inflammation and cancer.
- Epigenetic-modulating compounds are increasingly used in clinical settings.
Purpose of the Study:
- To evaluate the anti-inflammatory and anti-cancer properties of a novel quinazoline epigenetic modulator.
- To explore the compound's effects on gene expression in prostate cancer cell lines.
- To identify affected biological pathways and networks.
Main Methods:
- Utilized a non-hypothesis-driven transcriptomics approach with Affymetrix PrimeView® Human Gene Expression microarray.
- Analyzed gene expression data from PC3 and DU145 prostate cancer cell lines.
- Employed GATHER and IPA software for pathway and network analysis.
Main Results:
- Identified differentially expressed genes in both prostate cancer cell lines.
- Top canonical pathways affected included cholesterol biosynthesis, metabolism, and the mevalonate pathway.
- Observed significant modifications in biological processes, pathways, and networks.
Conclusions:
- The quinazoline compound exhibits anti-inflammatory and anti-cancer effects in prostate cancer models.
- Targeting sterol and mevalonate pathways represents a promising anti-cancer strategy.
- Epigenetic modulation offers a potential avenue for cancer therapy.
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