title: Dietary pterostilbene is a novel MTA1-targeted chemopreventive and therapeutic agent in prostate cancer.
abstract: Overexpression of the epigenetic modifier metastasis-associated protein 1 (MTA1) is associated with aggressive human prostate cancer. The purpose of this study was to determine MTA1- targeted chemopreventive and therapeutic efficacy of pterostilbene, a natural potent analog of resveratrol, in pre-clinical models of prostate cancer. Here, we show that high levels of MTA1 expression in Pten-loss prostate cooperate with key oncogenes, including c-Myc and Akt among others, to promote prostate cancer progression. Loss-of-function studies using human prostate cancer cells indicated direct involvement of MTA1 in inducing inflammation and epithelial-to-mesenchymal transition. Importantly, pharmacological inhibition of MTA1 by pterostilbene resulted in decreased proliferation and angiogenesis and increased apoptosis. This restrained prostatic intraepithelial neoplasia (PIN) formation in prostate-specific Pten heterozygous mice and reduced tumor development and progression in prostate-specific Pten-null mice. Our findings highlight MTA1 as a key upstream regulator of prostate tumorigenesis and cancer progression. More significantly, it offers pre-clinical proof for pterostilbene as a promising lead natural agent for MTA1-targeted chemopreventive and therapeutic strategy to curb prostate cancer.
authors.affiliation: Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Dhar
authors.affiliation: Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Avinash
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.|Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Liangfen
authors.initials: L
authors.lastname: Zhang
authors.affiliation: United States Department of Agriculture, Agriculture Research Service, Natural Product Utilization Research Unit, University, MS, USA.
authors.forename: Agnes M
authors.initials: AM
authors.lastname: Rimando
authors.affiliation: Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Janice M
authors.initials: JM
authors.lastname: Lage
authors.affiliation: Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Jack R
authors.initials: JR
authors.lastname: Lewin
authors.affiliation: Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.|Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Azeddine
authors.initials: A
authors.lastname: Atfi
authors.affiliation: Center of Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.|Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA.|Current affiliation: Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA.
authors.forename: Anait S
authors.initials: AS
authors.lastname: Levenson
mesh_terms: D000818:Animals; D018890:Chemoprevention; D006655:Histone Deacetylases / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058990:Molecular Targeted Therapy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D011897:Random Allocation; D012097:Repressor Proteins / Q000096:biosynthesis*; D013267:Stilbenes / Q000494:pharmacology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: C089320:MTA1 protein, human; C503336:Mta1 protein, mouse; D012097:Repressor Proteins; D013267:Stilbenes; D015534:Trans-Activators; D014157:Transcription Factors; C107773:pterostilbene; D006655:Histone Deacetylases
keywords: MTA1; chemoprevention; prostate cancer; pterostilbene; therapy