Effects of tocopherols and 2,2′-carboxyethyl hydroxychromans on phorbol-ester-stimulated neutrophils

Varga, Zsuzsa; Kosaras, Eszter; Komódi, Edina; Katkó, Mónika; Kárpáti, István; Balla, József; Paragh, G; Aisa, Maria Cristina; Galli, Francesco

doi:10.1016/j.jnutbio.2007.05.002

Cited by 27 publications

(22 citation statements)

References 53 publications

(62 reference statements)

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“…PKC was the former component in the cell signaling that was identified to be controlled by vitamin E (Galli and Azzi 2010) and is the earliest kinase that responds in a concentration and time-dependent manner to vitamin E leading to signal transduction from the plasmalemma to downstream elements. Membrane translocation and activity of PKC are directly influenced by chromanols (Varga et al 2008), which may provide a mechanism to explain the close correlation between kinetics profiles of anti-proliferative signaling and uptake rate (i.e., relative concentration within the lipid bilayer) of vitamin E molecules (Betti et al 2006). Further anti-cancer mechanisms of T3 possibly associated with cell toxicity include the inhibition of angiogenesis that has been demonstrated both in vitro and in vivo (Miyazawa et al 2004).…”

Section: Metabolite Formation and Activitymentioning

confidence: 97%

“…CEHC metabolite bioactivity has so far been reported to include direct antioxidant and anti-inflammatory effects, and mild natriuretic function and even anti-proliferative activity have been described for c-CEHC. More recent work has suggested a role of CEHCs also in the control of PKC activity of neutrophils (Varga et al 2008).…”

Section: Metabolite Formation and Activitymentioning

confidence: 99%

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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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Section: Metabolite Formation and Activitymentioning

confidence: 97%

Section: Metabolite Formation and Activitymentioning

confidence: 99%

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

et al. 2011

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“…Enzymatic activities were determined by quantifying the superoxide anion production via monitoring the change in cytochrome c reduction at 550 nm over a 15-min period. Results were calculated as nanomoles of superoxide produced per million cells over 15 min for total superoxide production [24].…”

Section: Measurement Of Nicotinamide Adenine Dinucleotide Phosphate (mentioning

confidence: 99%

The anti-inflammatory effect of 2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol by targeting Lyn kinase in human neutrophils

Liao

Chien

Chen

et al. 2015

Chemico-Biological Interactions

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“…In contrast, both α-CEHC and γ-CEHC inhibited microglial PGE2 and nitrite production and reduced iNOS mRNA and protein expression; thus, both are effective in reducing these cytokine-stimulated inflammatory processes (78). In phorbol-ester-stimulated neutrophils, superoxide anion production was inhibited not only by α-tocopherol but also by γ-and δ-tocopherol as well as by α-, γ-, and δ-CEHC at physiological concentrations (243). This effect was mediated by the inhibition of the membrane translocation and activation of PKC, which is the key event in phorbol-ester-induced signaling ( Figure 5).…”

Section: Vitamin E Metabolites and Signal Transductionmentioning

confidence: 98%

Vitamin E: A Role in Signal Transduction

Zingg

2015

Annu. Rev. Nutr.

109

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Vitamin E modulates the activity of several signal transduction enzymes with consequent alterations of gene expression. At the molecular level, vitamin E may directly bind to these enzymes and compete with their substrates, or it may change their activity by redox regulation. The translocation of several of these enzymes to the plasma membrane is regulated by vitamin E, suggesting the modulation of protein-membrane interactions as a common mechanism for vitamin E action. Enzyme-membrane interactions can be affected by vitamin E by interference with binding to specific membrane lipids or by altering cellular structures such as membrane microdomains (lipid rafts). Moreover, competition by vitamin E for common binding sites within lipid transport proteins may alter the traffic of lipid mediators and thus affect their signaling and enzymatic conversion. In this review, the main effects of vitamin E on enzymes involved in signal transduction are summarized and possible molecular mechanisms leading to enzyme modulation are evaluated.

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Effects of tocopherols and 2,2′-carboxyethyl hydroxychromans on phorbol-ester-stimulated neutrophils

Cited by 27 publications

References 53 publications

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

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

The anti-inflammatory effect of 2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol by targeting Lyn kinase in human neutrophils

Vitamin E: A Role in Signal Transduction

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