?-Tocopherol inhibits the development of prostate adenocarcinoma in prostate specific Pten-/- mice.

ABSTRACT: The PTEN/PI3K/AKT axis plays a critical role in regulating cell growth, differentiation and survival. Activation of this signaling pathway is frequently found in human cancers. Our previous studies demonstrated that ?-tocopherol (?-T) attenuates the activation of AKT by growth factor in prostate cancer cell lines, leading to inhibition of proliferation and induction of apoptosis. Herein, we investigated whether ?-T inhibits the development of prostate adenocarcinoma in prostate-specific Pten-/- (Ptenp-/-) mice in which the activation of AKT is the major driving force for tumorigenesis. By feeding Ptenp-/- mice with AIN93M or 0.2% ?-T supplemented diet starting at the age of 6 or 12 weeks, we found that ?-T treatment reduced prostate adenocarcinoma multiplicity at the age of 40 weeks by 53.3 and 42.7%, respectively. Immunohistochemical (IHC) analysis demonstrated that the phosphorylation of AKT (T308) was reduced in the prostate of the mice administered the ?-T diet. Consistently, proliferation was reduced and apoptosis was increased in prostate lesions of mice on the ?-T diet. Oxidative stress, as determined by IHC staining of 8-OH-dG, was not altered during prostate tumorigenesis, nor was it affected by administration of ?-T. In contrast, ?-tocopherol (?-T) at 0.2% in the diet did not affect prostate adenocarcinoma multiplicity in the Ptenp-/- mice. This finding is consistent with data from our previous study that ?-T, but not ?-T, inhibits the activation of AKT and the growth of prostate cancer cells. Together, these results demonstrate that ?-T inhibits the development of prostate adenocarcinoma in Ptenp-/- mice, mainly through inhibition of AKT activation.

SUBMITTER: Wang H 

PROVIDER: S-EPMC5862254 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature