Dietary Pterostilbene is a Novel MTA1-targeted Chemopreventive and Therapeutic Agent in Prostate Cancer

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Mar 5

PMID 26943043

Citations 38

Authors

Swati Dhar

Avinash Kumar

Liangfen Zhang

Agnes M Rimando

Janice M Lage

Jack R Lewin

Azeddine Atfi

Xu Zhang

Anait S Levenson

Affiliations

Soon will be listed here.

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.

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