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Oncotarget. 2016 Apr 5;7(14):18469-84. doi: 10.18632/oncotarget.7841.

Dietary pterostilbene is a novel MTA1-targeted chemopreventive and therapeutic agent in prostate cancer.

Author information

1
Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.
2
Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA.
3
United States Department of Agriculture, Agriculture Research Service, Natural Product Utilization Research Unit, University, MS, USA.
4
Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS, USA.
5
Center of Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, MS, USA.
6
Current affiliation: Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA.

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.

KEYWORDS:

MTA1; chemoprevention; prostate cancer; pterostilbene; therapy

PMID:
26943043
PMCID:
PMC4951302
DOI:
10.18632/oncotarget.7841
[Indexed for MEDLINE]
Free PMC Article

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