Abstract 3199: Pterostilbene supresses prostate cancer progression in transgenic mice model

Metastasis-associated protein 1 (MTA1) is a cancer progression-related epigenetic modifier whose overexpression is associated with aggressive prostate cancer (PCa), disease recurrence and metastasis in men. We previously found that MTA1 expression is significantly increased in Pten-null murine cells, and that resveratrol and its analogues inhibit MTA1 expression. In the current study, we used the murine Pten knockout PCa model to evaluate the effect of pterostilbene (PTER) on MTA1-mediated events in PCa progression. Pterostilbene is a potent natural analogue of resveratrol with improved pharmacokinetic properties and superior pharmacological potency. The Pten conditional knockout mice that mimic human disease and provide fast stage-defined development of PCa were fed, starting at 3 weeks of age, with phytoestrogen-free diet AIN 76A and injected daily (i.p.) either with 10% DMSO (control, untreated) or with 10 mg/kg bw PTER until 6, 10, 15 and 25 weeks of age. At necropsy, mouse prostates were formalin-fixed and paraffin-embedded for histological and immunohistochemical analysis. For protein analysis, mouse prostate dissection was performed to distinguish anterior prostate (AP) and dorso-latero-ventral (DLV) lobes. Our results showed that the PTER-treated group had a lower tumor grade and higher incidence of prostate intraepithelial neoplasia (PIN) at the expense of a substantial decrease in adenocarcinoma incidence. Prostate tissues from the PTER-treated group presented a decrese in Ki67 proliferation marker-positive cells and an increase in apoptosis. As potential mechanisms of PTER efficacy, 50-75% decrease in MTA1 and pAkt levels were observed at different time points. In addition, PTER inhibited androgen receptor (AR) expression, especially in the AP. Taken together, our findings suggest that PTER blocks PCa growth and progression at PIN stage in Pten conditional knockout mice model through inhibition of MTA1-Akt axis. Citation Format: Liangfen Zhang, Swati Dhar, Agnes M. Rimando, Avinash Kumar, Janice Lage, Jack R. Lewin, Xu Zhang, Anait S. Levenson. Pterostilbene supresses prostate cancer progression in transgenic mice model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3199. doi:10.1158/1538-7445.AM2014-3199