Tocotrienol is the most effective vitamin E for reducing endothelial expression of adhesion molecules and adhesion to monocytes

Theriault, André; Chao, Jun-Tzo; Gapor, Abeli

doi:10.1016/s0021-9150(01)00540-8

Cited by 106 publications

(63 citation statements)

References 37 publications

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“…The mechanism underlying apoptosis induction by g-T3H has not been studied, but appears to differ from that involved in the action of a-TOS. One possibility is that g-T3H acts via inhibition of prenylation (Theriault et al, 2002). Indeed, other compounds, which block prenylation, have been shown to be strong apoptogens (Miquel et al, 1998;Rioja et al, 2000).…”

Section: Resultsmentioning

confidence: 99%

Vitamin E analogues as inducers of apoptosis: structure–function relation

et al. 2003

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Recent results show that a-tocopheryl succinate (a-TOS) is a proapoptotic agent with antineoplastic activity. As modifications of the vitamin E (VE) molecule may affect its apoptogenic activity, we tested a number of newly synthesised VE analogues using malignant cell lines. Analogues of a-TOS with lower number of methyl substitutions on the aromatic ring were less active than a-TOS. Replacement of the succinyl group with a maleyl group greatly enhanced the activity, while it was lower for the glutaryl esters. Methylation of the free succinyl carboxyl group on a-TOS and d-TOS completely prevented the apoptogenic activity of the parent compounds. Both Trolox and its succinylated derivative were inactive. a-tocotrienol (a-T3 H) failed to induce apoptosis, while g-T3 H was apoptogenic, and more so when succinylated. Shortening the aliphatic side chain of g-T3 by one isoprenyl unit increased its activity. Neither phytyl nor oleyl succinate caused apoptosis. These findings show that modifications of different functional moieties of the VE molecule can enhance apoptogenic activity. It is hoped that these observations will lead to the synthesis of analogues with even higher apoptogenic and, consequently, antineoplastic efficacy.

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Section: Resultsmentioning

confidence: 99%

Vitamin E analogues as inducers of apoptosis: structure–function relation

et al. 2003

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“…Specificity of T3 signaling includes the control of this latter protein kinase (Eitsuka et al 2006) as well as of other kinases such as PI3K/Akt (Shah and Sylvester 2004;Shibata et al 2008;Uto-Kondo et al 2009) and ERK-MAPK (Sun et al 2008) and cyclin-dependent kinases (Elangovan et al 2008). Other discrete signals could be generated through the regulation of enzymes such as HMG-CoA reductase, the key step in cholesterol biosynthesis with a proposed role in inflammatory, endothelial, and cancer cell signaling (Theriault et al 2002) that appears to be regulated by T3 at the post-translational level (Parker et al 1993;Song and DeBose-Boyd 2006). Telomerase activity, a downstream component of the PKC signaling, may play a role in the T3-dependent control of cell proliferation and lifespan (Eitsuka et al 2006).…”

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confidence: 99%

Why tocotrienols work better: insights into the in vitro anti-cancer mechanism of vitamin E

et al. 2011

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The selective constraint of liver uptake and the sustained metabolism of tocotrienols (T3) demonstrate the need for a prompt detoxification of this class of lipophilic vitamers, and thus the potential for cytotoxic effects in hepatic and extra-hepatic tissues. Hypomethylated (c and d) forms of T3 show the highest in vitro and in vivo metabolism and are also the most potent natural xenobiotics of the entire vitamin E family of compounds. These stimulate a stress response with the induction of detoxification and antioxidant genes. Depending on the intensity of this response, these genes may confer cell protection or alternatively they stimulate a senescence-like phenotype with cell cycle inhibition or even mitochondrial toxicity and apoptosis. In cancer cells, the uptake rate and thus the cell content of these vitamers is again higher for the hypomethylated forms, and it is the critical factor that drives the dichotomy between protection and toxicity responses to different T3 forms and doses. These aspects suggest the potential for marked biological activity of hypomethylated ''highly metabolized'' T3 that may result in cytoprotection and cancer prevention or even chemotherapeutic effects. Cytotoxicity and metabolism of hypomethylated T3 have been extensively investigated in vitro using different cell model systems that will be discussed in this review paper as regard molecular mechanisms and possible relevance in cancer therapy.Keywords Tocotrienols Á Vitamin E Á Breast cancer Á Antioxidants Á Apoptosis Á Cell signaling Á Inflammation Á Metabolism Á Gene expression Á Cell redox T3 structure-function and specificity of actionIn the vitamin E family of molecules, tocotrienols (T3) are often considered of minor importance since these are less abundant than a and c tocopherol (TOH) in the circulation and in solid tissues. This has contributed to hinder our knowledge on the biological functions of this group of vitamers that is now regaining great interest, thanks to a number of recent studies that suggested health-promoting functions related with the cholesterol-lowering, cytoprotective, and anticarcinogenic effects of T3 [reviewed in (Aggarwal et al. (2010)].Structure-function studies demonstrate that many of these functions are more potent when the unsaturated (isoprenyl) side chain of T3 is combined with a hypomethylated (HM) chroman ring. The unsaturated chain characteristic of all the T3 forms confers well-defined physical and chemical characteristics that appear to include vitamer-specific interactions with other lipids and cell proteins (Atkinson

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“…Even though many in-vitro studies have reported tocotrienol's beneficial effect on adhesion molecules expression (Ahn et al, 2007;Naito et al, 2005;Theriault et al, 2002), ours is the only study that evaluated its role in human. However, the homocysteine elevation seen with TTMF treatment when compared to the baseline is in disagreement with a study in animals, which have demonstrated a beneficial lowering of homocysteine with tocotrienol treatment (Norsidah et al, 2013).…”

Section: Tocotrienol-tocopherol and Vitamin C In Hypercholesterolaemimentioning

confidence: 91%

Effects of adding tocotrienol-tocopherol mixed fraction and vitamin C on inflammatory status in hypercholesterolaemic patients in the low coronary risk category

et al. 2016

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Abstract-Aim:This study is designed to investigate the effects of tocotrienol-tocopherol mixed fraction (TTMF), vitamin C and combined TTMF-vitamin C supplementations on serum lipids and biochemical markers of inflammation and endothelial activation in hypercholesterolemic subjects in the low-risk category. Materials and Methods: 78 hypercholesterolaemic subjects (total cholesterol of  5.2 mmol/L and low-density lipoprotein 3.4 -4.9 mmol/L) in the low cardiovascular risk category according to the NCEP-ATP3 criteria were recruited. They were randomized into four treatment combination groups for a period of twelve months; (1) receiving TTMF and vitamin C, (2) receiving TTMF and placebo, (3) receiving vitamin C and placebo, and (4) receiving placebo for both. Serum fasting lipid profiles and levels of high-sensitivity C-reactive protein, interleukin-6, tumour necrosis factor-, intercellular adhesion molecule, vascular cell adhesion molecule, E-selectin and homocysteine were measured at entry and multiple time points post-randomisation. Results: There were no significant differences in percentage changes of lipid profiles and inflammatory markers between treated and placebo groups for either single or combined antioxidants supplementations. Conclusion: TTMF, vitamin C and combined TTMF-vitamin C supplementations have neutral effects on lipid profiles and biochemical markers of inflammation and endothelial activation in low risk subjects, suggesting that they offer no added advantage in the low cardiovascular risk group.

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Tocotrienol is the most effective vitamin E for reducing endothelial expression of adhesion molecules and adhesion to monocytes

Cited by 106 publications

References 37 publications

Vitamin E analogues as inducers of apoptosis: structure–function relation

Vitamin E analogues as inducers of apoptosis: structure–function relation

Why tocotrienols work better: insights into the in vitro anti-cancer mechanism of vitamin E

Effects of adding tocotrienol-tocopherol mixed fraction and vitamin C on inflammatory status in hypercholesterolaemic patients in the low coronary risk category

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