1. Academic Validation
  2. δ-Tocopherol inhibits the development of prostate adenocarcinoma in prostate specific Pten-/- mice

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

  • Carcinogenesis. 2018 Feb 9;39(2):158-169. doi: 10.1093/carcin/bgx128.
Hong Wang 1 Xu Yang 1 Anna Liu 1 Guocan Wang 2 Maarten C Bosland 3 Chung S Yang 1
Affiliations

Affiliations

  • 1 Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, USA.
  • 2 Department of Cancer Biology, MD Anderson Cancer Center, Houston, USA.
  • 3 Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, USA.
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 δ-tocopherol (δ-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 δ-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% δ-T supplemented diet starting at the age of 6 or 12 weeks, we found that δ-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 δ-T diet. Consistently, proliferation was reduced and Apoptosis was increased in prostate lesions of mice on the δ-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 δ-T. In contrast, α-tocopherol (α-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 δ-T, but not α-T, inhibits the activation of Akt and the growth of prostate Cancer cells. Together, these results demonstrate that δ-T inhibits the development of prostate adenocarcinoma in Ptenp-/- mice, mainly through inhibition of Akt activation.

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