2009
Maioli, Emanuela; Greci, Lucedio; Soucek, Karel; Hyzdalova, Martina; Pecorelli, Alessandra; Fortino, Vittoria; Valacchi, Giuseppe
Rottlerin inhibits ROS formation and prevents NFkappaB activation in MCF-7 and HT-29 cells. Journal Article
In: Journal of biomedicine & biotechnology, vol. 2009, pp. 742936, 2009, ISSN: 1110-7251 1110-7243, (Place: United States).
Abstract | Links | BibTeX | Tags: Acetophenones/chemistry/*pharmacology, Benzopyrans/chemistry/*pharmacology, Biphenyl Compounds/metabolism, Cell Nucleus/drug effects/metabolism, DNA/metabolism, Electron Spin Resonance Spectroscopy, Free Radical Scavengers/pharmacology, Genetic/drug effects, HT29 Cells, Humans, Hydrogen Peroxide/metabolism, Intracellular Space/drug effects/metabolism, NF-kappa B/*metabolism, Picrates/metabolism, Protein Binding/drug effects, Protein Transport/drug effects, Reactive Oxygen Species/*metabolism, Spectrophotometry, Transcription, Transfection, Tumor Necrosis Factor-alpha/pharmacology, Ultraviolet
@article{maioli_rottlerin_2009,
title = {Rottlerin inhibits ROS formation and prevents NFkappaB activation in MCF-7 and HT-29 cells.},
author = {Emanuela Maioli and Lucedio Greci and Karel Soucek and Martina Hyzdalova and Alessandra Pecorelli and Vittoria Fortino and Giuseppe Valacchi},
doi = {10.1155/2009/742936},
issn = {1110-7251 1110-7243},
year = {2009},
date = {2009-01-01},
journal = {Journal of biomedicine & biotechnology},
volume = {2009},
pages = {742936},
abstract = {Rottlerin, a polyphenol isolated from Mallotus Philippinensis, has been recently used as a selective inhibitor of PKC delta, although it can inhibit many kinases and has several biological effects. Among them, we recently found that Rottlerin inhibits the Nuclear Factor kappaB (NFkappaB), activated by either phorbol esters or H(2)O(2). Because of the redox sensitivity of NFkappaB and on the basis of Rottlerin antioxidant property, we hypothesized that Rottlerin could prevent NFkappaB activation acting as a free radicals scavenger, as other natural polyphenols. The current study confirms the antioxidant property of Rottlerin against the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) in vitro and against oxidative stress induced by H(2)O(2) and by menadione in culture cells. We also demonstrate that Rottlerin prevents TNFalpha-dependent NFkappaB activation in MCF-7 cells and in HT-29 cells transfected with the NFkappaB-driven plasmid pBIIX-LUC, suggesting that Rottlerin can inhibit NFkappaB via several pathways and in several cell types.},
note = {Place: United States},
keywords = {Acetophenones/chemistry/*pharmacology, Benzopyrans/chemistry/*pharmacology, Biphenyl Compounds/metabolism, Cell Nucleus/drug effects/metabolism, DNA/metabolism, Electron Spin Resonance Spectroscopy, Free Radical Scavengers/pharmacology, Genetic/drug effects, HT29 Cells, Humans, Hydrogen Peroxide/metabolism, Intracellular Space/drug effects/metabolism, NF-kappa B/*metabolism, Picrates/metabolism, Protein Binding/drug effects, Protein Transport/drug effects, Reactive Oxygen Species/*metabolism, Spectrophotometry, Transcription, Transfection, Tumor Necrosis Factor-alpha/pharmacology, Ultraviolet},
pubstate = {published},
tppubtype = {article}
}
Rottlerin, a polyphenol isolated from Mallotus Philippinensis, has been recently used as a selective inhibitor of PKC delta, although it can inhibit many kinases and has several biological effects. Among them, we recently found that Rottlerin inhibits the Nuclear Factor kappaB (NFkappaB), activated by either phorbol esters or H(2)O(2). Because of the redox sensitivity of NFkappaB and on the basis of Rottlerin antioxidant property, we hypothesized that Rottlerin could prevent NFkappaB activation acting as a free radicals scavenger, as other natural polyphenols. The current study confirms the antioxidant property of Rottlerin against the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) in vitro and against oxidative stress induced by H(2)O(2) and by menadione in culture cells. We also demonstrate that Rottlerin prevents TNFalpha-dependent NFkappaB activation in MCF-7 cells and in HT-29 cells transfected with the NFkappaB-driven plasmid pBIIX-LUC, suggesting that Rottlerin can inhibit NFkappaB via several pathways and in several cell types.
2006
Davis, Paul A.; Polagruto, John A.; Valacchi, Giuseppe; Phung, Anh; Soucek, Karel; Keen, Carl L.; Gershwin, M. Eric
Effect of apple extracts on NF-kappaB activation in human umbilical vein endothelial cells. Journal Article
In: Experimental biology and medicine (Maywood, N.J.), vol. 231, no. 5, pp. 594–598, 2006, ISSN: 1535-3702 1535-3699, (Place: Switzerland).
Abstract | Links | BibTeX | Tags: Cell Line, Endothelial Cells/cytology/*metabolism, Flavonoids/*metabolism, Genes, Humans, I-kappa B Proteins/metabolism, Malus/*chemistry, NF-kappa B/*metabolism, NF-KappaB Inhibitor alpha, Plant Extracts/*metabolism, Reporter, Umbilical Veins/*cytology
@article{davis_effect_2006,
title = {Effect of apple extracts on NF-kappaB activation in human umbilical vein endothelial cells.},
author = {Paul A. Davis and John A. Polagruto and Giuseppe Valacchi and Anh Phung and Karel Soucek and Carl L. Keen and M. Eric Gershwin},
doi = {10.1177/153537020623100514},
issn = {1535-3702 1535-3699},
year = {2006},
date = {2006-05-01},
journal = {Experimental biology and medicine (Maywood, N.J.)},
volume = {231},
number = {5},
pages = {594–598},
abstract = {The mechanisms by which foods, such as fruit, are able to reduce the risk of chronic disease are still unclear. Several fruit products, including apples and apple juice, that are flavonoid-rich are reported to increase antioxidant levels in human subjects. This is supported by the finding from our previous studies that the chronic consumption of apple juice by human subjects reduced ex vivo low-density lipoprotein (LDL) oxidation; we hypothesized that this was due to the flavonoid in the apple juice, which, as we reported earlier, reduced in vitro LDL oxidation. To further explore whether the mixture of flavonoids and other phytochemicals in apples are biologically relevant antioxidants, we tested the effects of this flavonoid-rich apple extract (AE) on oxidant-related pathways in a model of the endothelium: human umbilical vascular endothelial cells (HU-VECs). The effects of AE on oxidant-responsive (i.e., tumor necrosis factor [TNF]-alpha-induced) nuclear factor (NF)- kappaB signaling in cell culture were assessed in transfected HUVECs by using a construct that expressed luciferase under the control of NF-kappaB. Incubation of HUVEC for 24 hrs with up to 10 mM (as gallic acid equivalents) of AE demonstrated no cytotoxicity, as determined by lactate dehydrogenase release, caspase 3 activation, and apoptosis marker-based FACS analysis. AE after a 24-hr incubation period at either 200 or 2000 nM showed a complex pattern of decreased basal and TNF-alpha-stimulated NF-kappaB signaling (63% maximal decrease) as assessed by luciferase activity in the transfected HUVECs, as well as by reduced levels of IkappaBalpha protein phosphorylation detected by Western blot analysis. We suggest that AE downregulates NF-kappaB signaling and that this is indicative of an antioxidant effect of the flavonoids present in AE.},
note = {Place: Switzerland},
keywords = {Cell Line, Endothelial Cells/cytology/*metabolism, Flavonoids/*metabolism, Genes, Humans, I-kappa B Proteins/metabolism, Malus/*chemistry, NF-kappa B/*metabolism, NF-KappaB Inhibitor alpha, Plant Extracts/*metabolism, Reporter, Umbilical Veins/*cytology},
pubstate = {published},
tppubtype = {article}
}
The mechanisms by which foods, such as fruit, are able to reduce the risk of chronic disease are still unclear. Several fruit products, including apples and apple juice, that are flavonoid-rich are reported to increase antioxidant levels in human subjects. This is supported by the finding from our previous studies that the chronic consumption of apple juice by human subjects reduced ex vivo low-density lipoprotein (LDL) oxidation; we hypothesized that this was due to the flavonoid in the apple juice, which, as we reported earlier, reduced in vitro LDL oxidation. To further explore whether the mixture of flavonoids and other phytochemicals in apples are biologically relevant antioxidants, we tested the effects of this flavonoid-rich apple extract (AE) on oxidant-related pathways in a model of the endothelium: human umbilical vascular endothelial cells (HU-VECs). The effects of AE on oxidant-responsive (i.e., tumor necrosis factor [TNF]-alpha-induced) nuclear factor (NF)- kappaB signaling in cell culture were assessed in transfected HUVECs by using a construct that expressed luciferase under the control of NF-kappaB. Incubation of HUVEC for 24 hrs with up to 10 mM (as gallic acid equivalents) of AE demonstrated no cytotoxicity, as determined by lactate dehydrogenase release, caspase 3 activation, and apoptosis marker-based FACS analysis. AE after a 24-hr incubation period at either 200 or 2000 nM showed a complex pattern of decreased basal and TNF-alpha-stimulated NF-kappaB signaling (63% maximal decrease) as assessed by luciferase activity in the transfected HUVECs, as well as by reduced levels of IkappaBalpha protein phosphorylation detected by Western blot analysis. We suggest that AE downregulates NF-kappaB signaling and that this is indicative of an antioxidant effect of the flavonoids present in AE.