title: A quinazoline-based HDAC inhibitor affects gene expression pathways involved in cholesterol biosynthesis and mevalonate in prostate cancer cells.
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.
authors.affiliation: Auckland Cancer Society Research Centre, University of Auckland, New Zealand. k.bishop@auckland.ac.nz.
authors.forename: Z
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Auckland Cancer Society Research Centre, University of Auckland, New Zealand. k.bishop@auckland.ac.nz.
authors.forename: K S
authors.initials: KS
authors.lastname: Bishop
authors.affiliation: Auckland Cancer Society Research Centre, University of Auckland, New Zealand. k.bishop@auckland.ac.nz.
authors.forename: H
authors.initials: H
authors.lastname: Sutherland
authors.affiliation: Discipline of Nutrition and Dietetics, University of Auckland, New Zealand.
authors.forename: G
authors.initials: G
authors.lastname: Marlow
authors.affiliation: Auckland Cancer Society Research Centre, University of Auckland, New Zealand. k.bishop@auckland.ac.nz.
authors.forename: P
authors.initials: P
authors.lastname: Murray
authors.affiliation: Auckland Cancer Society Research Centre, University of Auckland, New Zealand. k.bishop@auckland.ac.nz.
authors.forename: W A
authors.initials: WA
authors.lastname: Denny
authors.affiliation: Auckland Cancer Society Research Centre, University of Auckland, New Zealand. k.bishop@auckland.ac.nz and Discipline of Nutrition and Dietetics, University of Auckland, New Zealand.
authors.forename: L R
authors.initials: LR
authors.lastname: Ferguson
mesh_terms: D045744:Cell Line, Tumor; D002784:Cholesterol / Q000096:biosynthesis*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics*; D011799:Quinazolines / Q000494:pharmacology*; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D056572:Histone Deacetylase Inhibitors; D011799:Quinazolines; D002784:Cholesterol; D008798:Mevalonic Acid