Tocotrienols

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Paul W. Sylvester - One of the best experts on this subject based on the ideXlab platform.

  • sesamin synergistically potentiates the anticancer effects of γ tocotrienol in mammary cancer cell lines
    Fitoterapia, 2013
    Co-Authors: Mohamed R Akl, Nehad M Ayoub, Bilal S Abuasal, Amal Kaddoumi, Paul W. Sylvester
    Abstract:

    Abstract γ-Tocotrienol and sesamin are phytochemicals that display potent anticancer activity. Since sesamin inhibits the metabolic degradation of Tocotrienols, studies were conducted to determine if combined treatment with sesamin potentiates the antiproliferative effects of γ-tocotrienol on neoplastic mouse (+ SA) and human (MCF-7 and MDA-MB-231) mammary cancer cells. Results showed that treatment with γ-tocotrienol or sesamin alone induced a significant dose-responsive growth inhibition, whereas combination treatment with these agents synergistically inhibited the growth of + SA, MCF-7 and MDA-MB-231 mammary cancer cells, while similar treatment doses were found to have little or no effect on normal (mouse CL-S1 and human MCF-10A) mammary epithelial cell growth or viability. However, sesamin synergistic enhancement of γ-tocotrienol-induced anticancer effects was not found to be mediated from a reduction in γ-tocotrienol metabolism. Rather, combined treatment with subeffective doses of γ-tocotrienol and sesamin was found to induce G1 cell cycle arrest, and a corresponding decrease in cyclin D1, CDK2, CDK4, CDK6, phospho-Rb, and E2F1 levels, and increase in p27 and p16 levels. Additional studies showed that the antiproliferative effect of combination treatment did not initiate apoptosis or result in a decrease in mammary cancer cell viability. Taken together, these findings indicate that the synergistic antiproliferative action of combined γ-tocotrienol and sesamin treatment in mouse and human mammary cancer cells is cytostatic, not cytotoxic, and results from G1 cell cycle arrest.

  • Antiproliferative and Apoptotic Effects of Tocopherols and Tocotrienols on Preneoplastic and Neoplastic Mouse Mammary Epithelial Cells
    Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York N.Y.), 2008
    Co-Authors: Barry S. Mcintyre, Karen P. Briski, Abdul Gapor, Paul W. Sylvester
    Abstract:

    Studies were conducted to determine the comparative effects of tocopherols and Tocotrienols on preneoplastic (CL-S1), neoplastic (-SA), and highly malignant (+SA) mouse mammary epithelial cell growth and viability in vitro. Over a 5-day culture period, treatment with 0-120 microM alpha- and gamma-tocopherol had no effect on cell proliferation, whereas growth was inhibited 50% (IC50) as compared with controls by treatment with the following: 13, 7, and 6 microM tocotrienol-rich-fraction of palm oil (TRF); 55, 47, and 23 microM delta-tocopherol; 12, 7, and 5 microM alpha-tocotrienol; 8, 5, and 4 microM gamma-tocotrienol; or 7, 4, and 3 microM delta-tocotrienol in CL-S1, -SA and +SA cells, respectively. Acute 24-hr exposure to 0-250 microM alpha- or gamma-tocopherol (CL-S1, -SA, and +SA) or 0-250 microM delta-tocopherol (CL-S1) had no effect on cell viability, whereas cell viability was reduced 50% (LD50) as compared with controls by treatment with 166 or 125 microM delta-tocopherol in -SA and +SA cells, respectively. Additional LD50 doses were determined as the following: 50, 43, and 38 microM TRF; 27, 28, and 23 microM alpha-tocotrienol; 19, 17, and 14 microM gamma-tocotrienol; or 16, 15, or 12 microM delta-tocotrienol in CL-S1, -SA, and +SA cells, respectively. Treatment-induced cell death resulted from activation of apoptosis, as indicated by DNA fragmentation. Results also showed that CL-S1, -SA, and +SA cells preferentially accumulate Tocotrienols as compared with tocopherols, and this may partially explain why Tocotrienols display greater biopotency than tocopherols. These data also showed that highly malignant +SA cells were the most sensitive, whereas the preneoplastic CL-S1 cells were the least sensitive to the antiproliferative and apoptotic effects of Tocotrienols, and suggest that Tocotrienols may have potential health benefits in preventing and/or reducing the risk of breast cancer in women.

  • γ tocotrienol inhibits neoplastic mammary epithelial cell proliferation by decreasing akt and nuclear factor κb activity
    Experimental Biology and Medicine, 2005
    Co-Authors: Sumit Shah, Paul W. Sylvester
    Abstract:

    Tocotrienols, a subgroup within the vitamin E family of compounds, have been shown to display potent anticancer activity and inhibit preneoplastic and neoplastic mammary epithelial cell proliferation at treatment doses that have little or no effect on normal cell growth and function. However, the specific intracellular mechanisms mediating the antiproliferative effects of Tocotrienols are presently unknown. Because Akt and nuclear factor κB (NFκB) are intimately involved in mammary tumor cell proliferation and survival, studies were conducted to determine the effects of γ-tocotrienol on Akt and NFκB activity in neoplastic +SA mammary epithelial cells in vitro. Treatment with 0–8 μM γ-tocotrienol for 0–3 days caused a dose-responsive inhibition in +SA cell growth and mitotic activity, as determined by MTT colorimetric assay and proliferating cell nuclear antigen immunocytochemical staining, respectively. Studies also showed that treatment with 4 μM γ-tocotrienol, a dose that inhibited +SA cell growth by mo...

  • gamma tocotrienol inhibits neoplastic mammary epithelial cell proliferation by decreasing akt and nuclear factor kappab activity
    Experimental Biology and Medicine, 2005
    Co-Authors: Sumit Shah, Paul W. Sylvester
    Abstract:

    Tocotrienols, a subgroup within the vitamin E family of compounds, have been shown to display potent anticancer activity and inhibit preneoplastic and neoplastic mammary epithelial cell proliferation at treatment doses that have little or no effect on normal cell growth and function. However, the specific intracellular mechanisms mediating the antiproliferative effects of Tocotrienols are presently unknown. Because Akt and nuclear factor kappaB (NFkappaB) are intimately involved in mammary tumor cell proliferation and survival, studies were conducted to determine the effects of gamma-tocotrienol on Akt and NFkappaB activity in neoplastic +SA mammary epithelial cells in vitro. Treatment with 0-8 microM gamma-tocotrienol for 0-3 days caused a dose-responsive inhibition in +SA cell growth and mitotic activity, as determined by MTT colorimetric assay and proliferating cell nuclear antigen immunocytochemical staining, respectively. Studies also showed that treatment with 4 microM gamma-tocotrienol, a dose that inhibited +SA cell growth by more than 50% compared with that of untreated control cells, decreased intracellular levels of activated phosphotidylinositol 3-kinase-dependent kinase (PI3K)-dependent kinase 1 (phospho-PDK-1) and Akt, and reduced phospho-Akt kinase activity. Furthermore, these effects were not found to be associated with an increase in either phosphatase and tensin homologue deleted from chromosome 10 (PTEN) or protein phosphatase type 2A phosphatase activity. In addition, gamma-tocotrienol treatment was shown to decrease NFkappaB transcriptional activity, apparently by suppressing the activation of IkappaB-kinase-alpha/beta, an enzyme associated with inducing NFkappaB activation. In summary, these findings demonstrate that the antiproliferative effects of gamma-tocotrienol result, at least in part, from a reduction in Akt and NFkappaB activity in neoplastic +SA mammary epithelial cells.

  • tocotrienol induced caspase 8 activation is unrelated to death receptor apoptotic signaling in neoplastic mammary epithelial cells
    Experimental Biology and Medicine, 2004
    Co-Authors: Sumit Shah, Paul W. Sylvester
    Abstract:

    Tocotrienols, a subclass in the vitamin E family of compounds, have been shown to induce apoptosis by activating caspase-8 and caspase-3 in neoplastic mammary epithelial cells. Since caspase-8 activation is associated with death receptor apoptotic signaling, studies were conducted to determine the exact death receptor/ligand involved in tocotrienol-induced apoptosis. Highly malignant +SA mouse mammary epithelial cells were grown in culture and maintained in serum-free media. Treatment with 20 μM γ-tocotrienol decreased +SA cell viability by inducing apoptosis, as determined by positive terminal dUTP nick end labeling (TUNEL) immunocytochemical staining. Western blot analysis showed that γ-tocotrienol treatment increased the levels of cleaved (active) caspase-8 and caspase-3. Combined treatment with caspase inhibitors completely blocked tocotrienol-induced apoptosis. Additional studies showed that treatment with 100 ng/ml tumor necrosis factor-α (TNF-α), 100 ng/ml FasL, 100 ng/ml TNF-related apoptosis-indu...

Sumit Shah - One of the best experts on this subject based on the ideXlab platform.

  • γ tocotrienol inhibits neoplastic mammary epithelial cell proliferation by decreasing akt and nuclear factor κb activity
    Experimental Biology and Medicine, 2005
    Co-Authors: Sumit Shah, Paul W. Sylvester
    Abstract:

    Tocotrienols, a subgroup within the vitamin E family of compounds, have been shown to display potent anticancer activity and inhibit preneoplastic and neoplastic mammary epithelial cell proliferation at treatment doses that have little or no effect on normal cell growth and function. However, the specific intracellular mechanisms mediating the antiproliferative effects of Tocotrienols are presently unknown. Because Akt and nuclear factor κB (NFκB) are intimately involved in mammary tumor cell proliferation and survival, studies were conducted to determine the effects of γ-tocotrienol on Akt and NFκB activity in neoplastic +SA mammary epithelial cells in vitro. Treatment with 0–8 μM γ-tocotrienol for 0–3 days caused a dose-responsive inhibition in +SA cell growth and mitotic activity, as determined by MTT colorimetric assay and proliferating cell nuclear antigen immunocytochemical staining, respectively. Studies also showed that treatment with 4 μM γ-tocotrienol, a dose that inhibited +SA cell growth by mo...

  • gamma tocotrienol inhibits neoplastic mammary epithelial cell proliferation by decreasing akt and nuclear factor kappab activity
    Experimental Biology and Medicine, 2005
    Co-Authors: Sumit Shah, Paul W. Sylvester
    Abstract:

    Tocotrienols, a subgroup within the vitamin E family of compounds, have been shown to display potent anticancer activity and inhibit preneoplastic and neoplastic mammary epithelial cell proliferation at treatment doses that have little or no effect on normal cell growth and function. However, the specific intracellular mechanisms mediating the antiproliferative effects of Tocotrienols are presently unknown. Because Akt and nuclear factor kappaB (NFkappaB) are intimately involved in mammary tumor cell proliferation and survival, studies were conducted to determine the effects of gamma-tocotrienol on Akt and NFkappaB activity in neoplastic +SA mammary epithelial cells in vitro. Treatment with 0-8 microM gamma-tocotrienol for 0-3 days caused a dose-responsive inhibition in +SA cell growth and mitotic activity, as determined by MTT colorimetric assay and proliferating cell nuclear antigen immunocytochemical staining, respectively. Studies also showed that treatment with 4 microM gamma-tocotrienol, a dose that inhibited +SA cell growth by more than 50% compared with that of untreated control cells, decreased intracellular levels of activated phosphotidylinositol 3-kinase-dependent kinase (PI3K)-dependent kinase 1 (phospho-PDK-1) and Akt, and reduced phospho-Akt kinase activity. Furthermore, these effects were not found to be associated with an increase in either phosphatase and tensin homologue deleted from chromosome 10 (PTEN) or protein phosphatase type 2A phosphatase activity. In addition, gamma-tocotrienol treatment was shown to decrease NFkappaB transcriptional activity, apparently by suppressing the activation of IkappaB-kinase-alpha/beta, an enzyme associated with inducing NFkappaB activation. In summary, these findings demonstrate that the antiproliferative effects of gamma-tocotrienol result, at least in part, from a reduction in Akt and NFkappaB activity in neoplastic +SA mammary epithelial cells.

  • tocotrienol induced caspase 8 activation is unrelated to death receptor apoptotic signaling in neoplastic mammary epithelial cells
    Experimental Biology and Medicine, 2004
    Co-Authors: Sumit Shah, Paul W. Sylvester
    Abstract:

    Tocotrienols, a subclass in the vitamin E family of compounds, have been shown to induce apoptosis by activating caspase-8 and caspase-3 in neoplastic mammary epithelial cells. Since caspase-8 activation is associated with death receptor apoptotic signaling, studies were conducted to determine the exact death receptor/ligand involved in tocotrienol-induced apoptosis. Highly malignant +SA mouse mammary epithelial cells were grown in culture and maintained in serum-free media. Treatment with 20 μM γ-tocotrienol decreased +SA cell viability by inducing apoptosis, as determined by positive terminal dUTP nick end labeling (TUNEL) immunocytochemical staining. Western blot analysis showed that γ-tocotrienol treatment increased the levels of cleaved (active) caspase-8 and caspase-3. Combined treatment with caspase inhibitors completely blocked tocotrienol-induced apoptosis. Additional studies showed that treatment with 100 ng/ml tumor necrosis factor-α (TNF-α), 100 ng/ml FasL, 100 ng/ml TNF-related apoptosis-indu...

Mario Irano - One of the best experts on this subject based on the ideXlab platform.

  • normal phase high performance liquid chromatography method for the determination of tocopherols and Tocotrienols in cereals
    Journal of Agricultural and Food Chemistry, 2003
    Co-Authors: Gianfranco Panfili, Alessandra Fratianni, Mario Irano
    Abstract:

    The eight vitamers of vitamin E (α-, β-, γ-, and δ-tocopherols and -Tocotrienols) have different antioxidant and biological activities and have different distributions in foods. Some cereals, especially oat, rye, and barley, are good sources of Tocotrienols. A fast procedure for the determination of tocopherols and Tocotrienols (tocols) in cereal foods was developed. It involves sample saponification and extraction followed by normal phase high-performance liquid chromatography (HPLC). The results have been compared with those found by direct extraction without saponification. The method is sensitive and selective enough to be tested on a wide variety of cereal samples. The highest tocol levels were found in soft wheat and barley (∼75 mg/kg of dry weight). β-Tocotrienol is the main vitamer found in hulled and dehulled wheats (from 33 to 43 mg/kg of dry weight), γ-tocopherol predominates in maize (45 mg/kg of dry weight) ), and α-tocotrienol predominates in oat and barley (56 and 40 mg/kg of dry weight, re...

  • normal phase high performance liquid chromatography method for the determination of tocopherols and Tocotrienols in cereals
    Journal of Agricultural and Food Chemistry, 2003
    Co-Authors: Gianfranco Panfili, Alessandra Fratianni, Mario Irano
    Abstract:

    The eight vitamers of vitamin E (alpha-, beta-, gamma-, and delta-tocopherols and -Tocotrienols) have different antioxidant and biological activities and have different distributions in foods. Some cereals, especially oat, rye, and barley, are good sources of Tocotrienols. A fast procedure for the determination of tocopherols and Tocotrienols (tocols) in cereal foods was developed. It involves sample saponification and extraction followed by normal phase high-performance liquid chromatography (HPLC). The results have been compared with those found by direct extraction without saponification. The method is sensitive and selective enough to be tested on a wide variety of cereal samples. The highest tocol levels were found in soft wheat and barley ( approximately 75 mg/kg of dry weight). beta-Tocotrienol is the main vitamer found in hulled and dehulled wheats (from 33 to 43 mg/kg of dry weight), gamma-tocopherol predominates in maize (45 mg/kg of dry weight) ), and alpha-tocotrienol predominates in oat and barley (56 and 40 mg/kg of dry weight, respectively).

Gianfranco Panfili - One of the best experts on this subject based on the ideXlab platform.

  • normal phase high performance liquid chromatography method for the determination of tocopherols and Tocotrienols in cereals
    Journal of Agricultural and Food Chemistry, 2003
    Co-Authors: Gianfranco Panfili, Alessandra Fratianni, Mario Irano
    Abstract:

    The eight vitamers of vitamin E (α-, β-, γ-, and δ-tocopherols and -Tocotrienols) have different antioxidant and biological activities and have different distributions in foods. Some cereals, especially oat, rye, and barley, are good sources of Tocotrienols. A fast procedure for the determination of tocopherols and Tocotrienols (tocols) in cereal foods was developed. It involves sample saponification and extraction followed by normal phase high-performance liquid chromatography (HPLC). The results have been compared with those found by direct extraction without saponification. The method is sensitive and selective enough to be tested on a wide variety of cereal samples. The highest tocol levels were found in soft wheat and barley (∼75 mg/kg of dry weight). β-Tocotrienol is the main vitamer found in hulled and dehulled wheats (from 33 to 43 mg/kg of dry weight), γ-tocopherol predominates in maize (45 mg/kg of dry weight) ), and α-tocotrienol predominates in oat and barley (56 and 40 mg/kg of dry weight, re...

  • normal phase high performance liquid chromatography method for the determination of tocopherols and Tocotrienols in cereals
    Journal of Agricultural and Food Chemistry, 2003
    Co-Authors: Gianfranco Panfili, Alessandra Fratianni, Mario Irano
    Abstract:

    The eight vitamers of vitamin E (alpha-, beta-, gamma-, and delta-tocopherols and -Tocotrienols) have different antioxidant and biological activities and have different distributions in foods. Some cereals, especially oat, rye, and barley, are good sources of Tocotrienols. A fast procedure for the determination of tocopherols and Tocotrienols (tocols) in cereal foods was developed. It involves sample saponification and extraction followed by normal phase high-performance liquid chromatography (HPLC). The results have been compared with those found by direct extraction without saponification. The method is sensitive and selective enough to be tested on a wide variety of cereal samples. The highest tocol levels were found in soft wheat and barley ( approximately 75 mg/kg of dry weight). beta-Tocotrienol is the main vitamer found in hulled and dehulled wheats (from 33 to 43 mg/kg of dry weight), gamma-tocopherol predominates in maize (45 mg/kg of dry weight) ), and alpha-tocotrienol predominates in oat and barley (56 and 40 mg/kg of dry weight, respectively).

S Ratti - One of the best experts on this subject based on the ideXlab platform.

  • tocopherols and Tocotrienols as free radical scavengers in refined vegetable oils and their stability during deep fat frying
    Food Chemistry, 2007
    Co-Authors: M Rossi, C Alamprese, S Ratti
    Abstract:

    The aim of this study was to assess the effect of total tocopherols and Tocotrienols of refined vegetable oils on oil radical-scavenging activity and to investigate the stability of the various homologues during the deep-fat frying of French fries. Eight different refined vegetable oils were investigated, having variable levels of natural tocopherols and Tocotrienols. A direct correlation between the radical-scavenging capacity of the oils, measured by the DPPH test, and the total content of natural tocopherols and Tocotrienols was found. Frying experiments showed that the stability of the different tocopherols and Tocotrienols present in the refined vegetable oils basically depend on two factors: the fatty acid composition of the oil, in particular polyunsaturated fatty acid content, and the kind of tocopherol and tocotrienol homologues present. The more oxidizable the oil, on the basis of fatty acid composition, the more stable were the tocopherolic antioxidants. Among the different homologues, γ-tocotrienol in palm super olein proved to be the least stable during the deep-fat frying, thus preserving the other homologues.

  • tocopherols and Tocotrienols as free radical scavengers in refined vegetable oils and their stability during deep fat frying
    Food Chemistry, 2007
    Co-Authors: M Rossi, C Alamprese, S Ratti
    Abstract:

    The aim of this study was to assess the effect of total tocopherols and Tocotrienols of refined vegetable oils on oil radical-scavenging activity and to investigate the stability of the various homologues during the deep-fat frying of French fries. Eight different refined vegetable oils were investigated, having variable levels of natural tocopherols and Tocotrienols. A direct correlation between the radical-scavenging capacity of the oils, measured by the DPPH test, and the total content of natural tocopherols and Tocotrienols was found. Frying experiments showed that the stability of the different tocopherols and Tocotrienols present in the refined vegetable oils basically depend on two factors: the fatty acid composition of the oil, in particular polyunsaturated fatty acid content, and the kind of tocopherol and tocotrienol homologues present. The more oxidizable the oil, on the basis of fatty acid composition, the more stable were the tocopherolic antioxidants. Among the different homologues, γ-tocotrienol in palm super olein proved to be the least stable during the deep-fat frying, thus preserving the other homologues.