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Gamma Tocotrienol and Prostate Cancer: The Regulation of Two Independent Pathways to Potentiate Cell Growth Inhibition and ApoptosisCampbell, S., Whaley, S. G., Phillips, R., Aggarwal, B. B., Stimmel, J. B., Leesnitzer, L., Blanchard, S. G., Stone, W. L., Christian, Muenyi, Krishnan, K. 01 October 2008 (has links)
Dietary vitamin E, highly expressed in palm oil, exists as either tocopherols or tocotrienols. Evidence indicates that vitamin Es maybe potent cancer preventive agents. In this study, the y- and O- isoforms of vitamin E were found to he the most effective at cancer cell growth inhibition, with the tocotrienols being more effective than the tocopherols in androgen-independent PC-3 prostate cancer cells. To assure that these compounds were selective toward cancer cells, the growth arrest of PrEC normal prostate cells was compared to PC-3 cells. At concentrations of -30 iM dietary, y-vitamin Es showed no signficant growth arrest on PrEC cell growth, hut selectively inhibited growth in the PC-3 cancer cells. Moreover y-Tocotrienol demonstrated a greater potential to inhibit growth in cancer cells at these lower concentrations than did y-Tocopherol. Two independent pathways important in carcinogenesis were tested: PPAR y and NFicB. The PPAR y was up regulated by both dietary y-vitamin Es by the modulation of the endogenous ligand 15-S-HETE, while NFicB was only regulated by y-Tocotrienol. The modulation of NFicB was confirmed by the down regulation of the pro-Apoptotic proteins clAP, xIAP, and BcL-2 which potentiate apoptosis and are down stream effectors of NFicB.
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Vitamin E (Tocotrienols) and Prostate Cancer: A Proteomics Approach.Muenyi, Christian Mbangha 14 August 2007 (has links)
Proteomics is the large scale study of proteins in cells or organisms. The purpose of this study was to characterize the proteomic alterations occurring in a prostate cancer (LNCaP) cell line after treatment with delta-tocotrienol (a form of vitamin E not very prevalent from most dietary sources). We found that both gamma- and delta-tocotrienols induced time and concentration dependent growth inhibition and programmed cell dead (apoptosis) in LNCaP cells. Secondly, we used two-dimensional gel electrophoresis (2-DE) to characterize changes in protein expression levels associated with this treatment. Our results show that a specific set of proteins are regulated at both early and late times following treatment with delta-tocotrienol and these proteins have been characterized by their apparent molecular weights and isoelectric points. The alteration observed at early time points are particularly interesting because these changes are likely to reflect the underlying molecular mechanisms for triggering cancer cell death.
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Effects of Select Vitamin E Isoforms on the Production of Polyunsaturated Fatty Acid Metabolites in Colorectal CancerBorketey, Martha A 01 May 2015 (has links)
Vitamin E exhibits anti-tumor activity by regulating pathways in cancer cells, potentially the lipoxygenase (LOX) pathway. We studied the effects of alpha tocopherol (AT), gamma tocopherol (GT), gamma tocotrienol (GT3), and an alpha-gamma tocopherol mixture (ATGT) on the production of the LOX metabolites 13-hydroxyoctadecaenoic acid (HODE), 15-hydroxyeicosatetraenoic acid (HETE), 12-HETE, and 5-HETE in colorectal cancer. These metabolites were examined in the HCT-116 cell line after 24 h treatment with select vitamin E isoforms and quantified by LC/MS/MS. Under physiological conditions, we find that treatment with varying vitamin E isoforms have different effects on the production of 13-HODE, 15-HETE, 12-HETE, and 5-HETE. GT increases 13-HODE and decreases 12-HETE. AT reverses the effects of GT regulation on the LOX pathway, while GT3 has no significant effect on the metabolites tested. GT shows superiority in regulating the LOX pathway as it increases 13-HODE and decreases 12-HETE for possible prevention of colorectal cancer.
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