Dose Dependent Elevation of Plasma Tocotrienol Levels and Its Effect on Arterial Compliance, Plasma Total Antioxidant Status, and Lipid Profile in Healthy Humans Supplemented with Tocotrienol Rich Vitamin E

Rasool, Aida Hanum Ghulam; Yuen, Kah Hay; Yusoff, Khalid; Wong, Abdul Rahim; Rahman, Abdul Rashid Abdul

doi:10.3177/jnsv.52.473

Cited by 60 publications

(52 citation statements)

References 28 publications

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“…Purified TTs and ␣-TOC concentrations are reported in Table 1. Concentrations of TTs used in the experiements were in the micromolar order, which is a concentration that can be achieved in the human serum, as reported previously (36,53,76). Control cells were treated with the same volumes of DMSO and/or ethanol vehicle alone.…”

Section: Methodsmentioning

confidence: 99%

A novel mechanism of natural vitamin E tocotrienol activity: involvement of ERβ signal transduction

Comitato

Nesaretnam²,

Leoni³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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Vitamin E is a generic term used to indicate all tocopherol (TOC) and tocotrienol (TT) derivates. In the last few years, several papers have shown that a TT-rich fraction (TTRF) extracted from palm oil inhibits proliferation and induces apoptosis in a large number of cancer cells. However, the molecular mechanism(s) involved in TT action is still unclear. In the present study, we proposed for the first time a novel mechanism for TT activity that involves estrogen receptor (ER) signaling. In silico simulations and in vitro binding analyses indicated a high affinity of TTs for ER␤ but not for ER␣. In addition, in ER␤-containing MDA-MB-231 breast cancer cells, we demonstrated that TTs increase the ER␤ translocation into the nucleus, which in turn activates estrogen-responsive genes (MIC-1, EGR-1 and cathepsin D), as demonstrated by cell preincubation with the ER inhibitor ICI-182,780. Finally, we observed that TT treatment is associated with alteration of cell morphology, DNA fragmentation, and caspase-3 activation. Altogether, these experiments elucidated the molecular mechanism underling ␥-and ␦-TT effects.estrogen receptor-␤; breast cancer; apoptosis; tocopherol; nuclear receptor TOCOTRIENOLS (TTs) are usually included together with tocopherols (TOCs) within the "vitamin E family". TTs have a chemical structure similar to TOCs but present three double bonds at positions 3Ј, 7Ј, and 11Ј of the side chain. Similar to TOCs, TTs have four natural isomers, named as ␣, ␤, ␥, and ␦, that differ by the number and position of methyl groups on the chroman ring. The unsaturation of the side chain is associated with specific chemicophysical characteristics that are attracting growing interest both in the field of nutrition and in pharmacology (7, 62).TOCs are commonly found in high concentrations in vegetable oils, animal fats, grains, vegetables, and fruits (13), whereas TTs are relatively rare in Western diets and found in appreciable levels only in a few specific vegetable fats, such as palm oil and rice bran oil (48). The great bioavailability of TOCs and their high efficiency in acting as antioxidants have attracted the interest of biologists who have disregarded TTs and their properties. Recent investigations have demonstrated that the antioxidant efficacy of TTs in membranes is higher than that of TOCs (59, 66), although their uptake and distribution after oral ingestion are less than that of ␣-TOCs (9, 76). Moreover, TTs have been reported to have many specific activities, such as the suppression of growth and the induction of apoptosis in different human and mouse mammary cancer cells (8, 20, 27, 35, 39 -41, 57, 60, 67-69, 77) and in other human cancer cells (14,15,23,37,42,63,71). In general, TTs have been proposed to possess diverse properties that are often not exhibited by TOCs (58) and are associated with "anticancer" activity that is independent of their antioxidant properties.The molecular mechanisms underlying these beneficial effects are still scarcely understood. In our laboratory, we have previously rep...

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Section: Methodsmentioning

confidence: 99%

A novel mechanism of natural vitamin E tocotrienol activity: involvement of ERβ signal transduction

Comitato

Nesaretnam²,

Leoni³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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“…Concentrations reported for TTs and a-TOCO are related to the percentage present in the PTRF mixture. Concentrations of TTs used in the experiments were in the micromolar order, which is a concentration that can be achieved in the human serum, as described previously [16]. Control cells were treated with the same volumes of DMSO and/or ethanol vehicle alone.…”

Section: Cells Lines and Treatmentsmentioning

confidence: 99%

Tocotrienols activity in MCF‐7 breast cancer cells: Involvement of ERβ signal transduction

Comitato

Leoni

Canali

et al. 2010

Molecular Nutrition Food Res

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The term Vitamin E is utilized to describe eight molecules, subdivided into two groups, tocopherols and tocotrienols (TTs). It has been shown that specific TTs affect the growth of several lines of tumour cells, and that this activity is not shared by tocopherols. In agreement with these observations, a TTs-rich fraction from palm oil (PTRF) was reported to inhibit proliferation and induce apoptosis in several cancer cells. However, the molecular mechanism involved in TTs activity is still unclear. We have recently proposed that TTs pro-apoptotic activity involves estrogen receptor beta (ERbeta) signalling. In this study, we report that, in MCF-7 breast cancer cell, expressing both ERalpha and ERbeta, PTRF treatment increases ERbeta nuclear translocation, as demonstrated by immunofluorescence experiments and significantly inhibits ERalpha expression (-458.91-fold of change) and complete disappearing of the protein from the nucleus. Moreover, PTRF treatment induces ER-dependent genes expression (macrophage inhibitory cytokine-1, early growth response-1 and Cathepsin D) which is inhibited by the ER inhibitor, ICI 182.780, and induces DNA fragmentation. Finally, cDNA-array experiments suggest that the activation of specific pathways in cells treated with gamma-TT with respect to alpha-TT. Our data suggest a novel potential molecular mechanism for TTs activity.

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“…Rasool et al (2006) employed similar TTMF products at dosages 80, 160 and 320 mg daily for two months in healthy males and found that TTMF had neutral effects on arterial compliance, total antioxidant status and lipids [29]. The neutral effects of these combined supplementations on lipids and inflammation is further supported by another Chinese group.…”

Section: Discussionmentioning

confidence: 95%

A Randomized Pilot Study on the Effects of Combined Tocotrienol-Tocopherol Mixed Fraction and Vitamin C on Inflammatory Status and Lipid Profile in Statin-Treated High Risk Patients

Muid

et al. 2016

Int Arch Med

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Previous studies have suggested that combination of Tocotrienoltocopherol mixed fraction (TTMF) vitamin E and vitamin C supplementation act synergistically in vivo to enhance their anti-oxidant properties. However, additional effects beyond that of anti-oxidation of combined vitamin E and vitamin C in statin-treated high coronary risk patients remains unclear. The aim of this study was to investigate pleiotropic effects of TTMF and vitamin C on inflammatory biomarkers and lipid profile in statin-treated high coronary risk patients.This was a pilot, randomized, double-blind, placebo controlled clinical trial. Twenty nine high coronary risk hypercholesterolaemic subjects were randomized into TTMF+C (160mg TTMF, 75% tocotrienol: 25% alpha-tocopherol plus 500mg vitamin C) intervention or placebo groups for 12 months. Blood samples were collected at entry, baseline, 2 weeks, 3, 6 and 12 months post-randomization for analysis of inflammatory biomarkers [(high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumour necrosis factor alpha (TNFα)] and serum lipid profile [Total cholesterol (TC), low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c) and triglycerides (TG)]. There was no significant difference observed between TTMF+C and placebo groups with regards to percent change of hsCRP, IL-6 and TNF-α concentrations (p>0.05) and TC, at baseline, 2 weeks, 3, 6 and 12 months of intervention. There was also no significant change seen in the mean concentration of all inflammatory biomarkers and serum lipid profile between TTMF+C and placebo groups at all timelines. TTMF and vitamin C supplementation did not significantly improve the inflammatory status and lipid profile. This could in part be con-

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Dose Dependent Elevation of Plasma Tocotrienol Levels and Its Effect on Arterial Compliance, Plasma Total Antioxidant Status, and Lipid Profile in Healthy Humans Supplemented with Tocotrienol Rich Vitamin E

Cited by 60 publications

References 28 publications

A novel mechanism of natural vitamin E tocotrienol activity: involvement of ERβ signal transduction

A novel mechanism of natural vitamin E tocotrienol activity: involvement of ERβ signal transduction

Tocotrienols activity in MCF‐7 breast cancer cells: Involvement of ERβ signal transduction

A Randomized Pilot Study on the Effects of Combined Tocotrienol-Tocopherol Mixed Fraction and Vitamin C on Inflammatory Status and Lipid Profile in Statin-Treated High Risk Patients

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