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Depression: 21st Century Solutions + The Dark Side of Wheat

Abstract Title:

δ-Tocopherol inhibits receptor tyrosine kinase-induced AKT activation in prostate cancer cells.

Abstract Source:

Mol Carcinog. 2015 Oct 14. Epub 2015 Oct 14. PMID: 26465359

Abstract Author(s):

Hong Wang, Jungil Hong, Chung S Yang

Article Affiliation:

Hong Wang

Abstract:

The cancer preventive activity of vitamin E is suggested by epidemiological studies and supported by animal studies with vitamin E forms,γ-tocopherol and δ-tocopherol (δ-T). Several recent large-scale cancer prevention trials with high dose of α-tocopherol, however, yielded disappointing results. Whether vitamin E prevents or promotes cancer is a serious concern. A better understanding of the molecular mechanisms of action of thedifferent forms of tocopherols would enhance our understanding of this topic. In this study, we demonstrated that δ-T was the most effective tocopherol form in inhibiting prostate cancer cell growth, by inducing cell cycle arrest and apoptosis. By profiling the effects of δ-T on the cell signaling using the phospho-kinase array, we found that the most inhibited target was the phosphorylation of AKT on T308. Further study on the activation of AKT by EGFR and IGFR revealed that δ-T attenuated the EGF/IGF-induced activation of AKT (via the phosphorylation of AKT on T308 induced by the activation of PIK3). Expression of dominant active PIK3 and AKT in prostate cancer cell line DU145 in which PIK3, AKT, and PTEN are wild type caused the cells to be reflectory to the inhibition of δ-T, supporting that δ-T inhibits the PIK3-mediated activation of AKT. Our data also suggest that δ-T interferes with the EGF-induced EGFR internalization, which leads to the inhibition of the receptor tyrosine kinase-dependent activation of AKT. In summary, our results revealed a novel mechanism of δ-T in inhibiting prostate cancer cell growth, supporting the cancer preventive activity δ-T. © 2015 Wiley Periodicals, Inc.

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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