| First Author | Dhar S | Year | 2016 |
| Journal | Oncotarget | Volume | 7 |
| Issue | 14 | Pages | 18469-84 |
| PubMed ID | 26943043 | Mgi Jnum | J:316025 |
| Mgi Id | MGI:6832218 | Doi | 10.18632/oncotarget.7841 |
| Citation | Dhar S, et al. (2016) Dietary pterostilbene is a novel MTA1-targeted chemopreventive and therapeutic agent in prostate cancer. Oncotarget 7(14):18469-84 |
| abstractText | 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. |
