Abstract 5247: δ-Tocopherol inhibits the development of prostate adenocarcinoma in prostate specific Pten-/- mice

Abstract

Abstract PTEN/PI3K/AKT axis plays a critical role in regulating cell growth, metabolism, migration, differentiation, and survival. Activation of this signal pathway is frequently found in human cancers. Data from our previous studies demonstrated that δ-tocopherol (δ-T) attenuates the activation of AKT by growth factor in prostate cancer cell lines, leading to inhibiting proliferation and inducing apoptosis. Herein, we investigated whether δ-T is able to inhibit the development of prostate adenocarcinoma in prostate-specific Pten-/- (Ptenp-/-) mice, in which the activation of AKT resulted from loss of Pten is the driver. By feeding Ptenp-/- mice with the AIN93M or 0.2% δ-T supplemented diet starting at the age of 6 or 12 weeks, we found that, at the age of 40 weeks, δ-T treatment reduced the number of invasive prostate adenocarcinoma by 53.3% (p<0.005) and 42.7% (p<0.001), respectively. By immunohistochemical analysis, the activation of AKT via phosphorylation of AKT(T308) was found reduced in the prostate of the mice on δ-T diet. Consistently, proliferation was reduced and apoptosis was increased in prostate of the mice on δ-T diet. We also determined oxidative stress by immunohistochemical staining of 8-OH-dG and nitro-tyrosine, and found that these markers were not altered during prostate tumorigenesis, nor they were affected by δ-T. A 0.2% α-tocopherol diet was also used to feed Ptenp-/- mice, but did not inhibit the development of prostate adenocarcinoma, consistent with previous data demonstrating that α-tocopherol did not inhibit the activation of AKT. Together, these results support that δ-T is effective in supressing the development of prostate adenocarcinoma in Ptenp-/- mice through inhibition of AKT activation. Citation Format: Xu Yang, Wang Hong, Guocan Wang, Anna Liu, Maarten c. Bosland, Chung s. Yang. δ-Tocopherol inhibits the development of prostate adenocarcinoma in prostate specific Pten-/- mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5247. doi:10.1158/1538-7445.AM2017-5247