Nutritional flavonoids impact on nuclear and extranuclear estrogen receptor activities

Galluzzo, Paola; Marino, Maria

doi:10.1007/bf02829966

Cited by 49 publications

(51 citation statements)

References 156 publications

(216 reference statements)

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“…Among the most studied flavonoids with respect to antitumor functions are genistein and quercetin. Phytoestrogens have been considered a natural alternative to the hormone replacement therapy because these chemicals are found in the regular diet (12). Genistein is mostly present in soybeans.…”

mentioning

confidence: 99%

Quantitative Proteomics and Transcriptomics Addressing the Estrogen Receptor Subtype-mediated Effects in T47D Breast Cancer Cells Exposed to the Phytoestrogen Genistein

Sotoca

Gelpke²,

Boeren

et al. 2011

Molecular & Cellular Proteomics

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The present study addresses, by transcriptomics and quantitative stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics, the estrogen receptor ␣ (ER␣) and ␤ (ER␤)-mediated effects on gene and protein expression in T47D breast cancer cells exposed to the phytoestrogen genistein. Using the T47D human breast cancer cell line with tetracycline-dependent ER␤ expression (T47D-ER␤), the effect of a varying intracellular ER␣/ ER␤ ratio on genistein-induced gene and protein expression was characterized. Results obtained reveal that in ER␣-expressing T47D-ER␤ cells with inhibited ER␤ expression genistein induces transcriptomics and proteomics signatures pointing at rapid cell growth and migration by dynamic activation of cytoskeleton remodeling. The data reveal an interplay between integrins, focal adhesion kinase, CDC42, and actin cytoskeleton signaling cascades, occurring upon genistein treatment, in the T47D-ER␤ breast cancer cells with low levels of ER␣ and no expression of ER␤. In addition, data from our study indicate that ER␤-mediated gene and protein expression counteracts ER␣-mediated effects because in T47D-ER␤ cells expressing ER␤ and exposed to genistein transcriptomics and proteomics signatures pointing at a clear down-regulation of cell growth and induction of cell cycle arrest and apoptosis were demonstrated. These results suggest that ER␤ decreases cell motility and metastatic potential as well as cell survival of the breast cancer cell line. It is concluded that the effects of genistein on proteomics and transcriptomics end points in the T47D-ER␤ cell model are comparable with those reported previously for estradiol with the ultimate estrogenic effect being dependent on the relative affinity for both receptors and on the receptor phenotype (ER␣/ER␤ ratio)

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confidence: 99%

Quantitative Proteomics and Transcriptomics Addressing the Estrogen Receptor Subtype-mediated Effects in T47D Breast Cancer Cells Exposed to the Phytoestrogen Genistein

Sotoca

Gelpke²,

Boeren

et al. 2011

Molecular & Cellular Proteomics

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“…Most of these effects have been obtained by using variable Nar concentrations ranging from 1 to 100 lM. We recently reported that Nar concentrations (1-10 lM), achievable in human plasma after a meal rich in flavonoids (i.e., tomatoes, oranges, and grapefruit juice typical of Mediterranean diet), exert protective pro-apoptotic effects against estrogen-related cancers (Galluzzo and Marino 2006;Bulzomi et al 2012Bulzomi et al , 2010. Nar binds to both estrogen receptors (i.e., ERa and ERb) (Kuiper et al 1998;Bulzomi et al 2012) and acts as a mimetic of 17b-estradiol (E2), the most active among estrogens, activating a pro-apoptotic cascade in the presence of ERb subtype Galluzzo and Marino 2006;Marino et al 2012).…”

Section: Introductionmentioning

confidence: 99%

“…We recently reported that Nar concentrations (1-10 lM), achievable in human plasma after a meal rich in flavonoids (i.e., tomatoes, oranges, and grapefruit juice typical of Mediterranean diet), exert protective pro-apoptotic effects against estrogen-related cancers (Galluzzo and Marino 2006;Bulzomi et al 2012Bulzomi et al , 2010. Nar binds to both estrogen receptors (i.e., ERa and ERb) (Kuiper et al 1998;Bulzomi et al 2012) and acts as a mimetic of 17b-estradiol (E2), the most active among estrogens, activating a pro-apoptotic cascade in the presence of ERb subtype Galluzzo and Marino 2006;Marino et al 2012). On the other hand, Nar selectively impairs the membrane-initiating signals of ERa subtype important for cell cycle progression (Virgili et al 2004;Galluzzo and Marino 2006;Galluzzo et al 2008;Marino et al 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Nar binds to both estrogen receptors (i.e., ERa and ERb) (Kuiper et al 1998;Bulzomi et al 2012) and acts as a mimetic of 17b-estradiol (E2), the most active among estrogens, activating a pro-apoptotic cascade in the presence of ERb subtype Galluzzo and Marino 2006;Marino et al 2012). On the other hand, Nar selectively impairs the membrane-initiating signals of ERa subtype important for cell cycle progression (Virgili et al 2004;Galluzzo and Marino 2006;Galluzzo et al 2008;Marino et al 2012).…”

Section: Introductionmentioning

confidence: 99%

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Naringenin modulates skeletal muscle differentiation via estrogen receptor α and β signal pathway regulation

et al. 2014

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Several experiments sustain healthful benefits of the flavanone naringenin (Nar) against chronic diseases including its protective effects against estrogen-related cancers. These experiments encourage Nar use in replacing estrogen treatment in post-menopausal women avoiding the serious side effects ascribed to this hormone. However, at the present, scarce data are available on the impact of Nar on E2-regulated cell functions. This study was aimed at determining the impact of Nar on the estrogen receptor (ERa and b)-dependent signals important for 17b-estradiol (E2) effect in muscle cells (rat L6 myoblasts, mouse C2C12 myoblasts, and mouse skeletal muscle satellite cells). Dietary relevant concentration of Nar delays the appearance of skeletal muscle differentiation markers (i.e., GLUT4 translocation, myogenin, and both fetal and slow MHC isoforms) and impairs E2 effects specifically hampering ERa ability to activate AKT. Intriguingly, Nar effects are specific for E2-initiating signals because IGF-Iinduced AKT activation, and myoblast differentiation markers were not affected by Nar treatment. Only 7 days after Nar stimulation, early myoblast differentiation markers (i.e., myogenin, and fetal MHC) start to be accumulated in myoblasts. On the other hand, Nar stimulation activates, via ERb, the phosphorylation of p38/MAPK involved in reducing the reactive oxygen species formation in skeletal muscle cells. As a whole, data reported here strongly sustain that although Nar action mechanisms include the impairment of ERa signals which drive muscle cells to differentiation, the effects triggered by Nar in the presence of ERb could balance this negative effect avoiding the toxic effects produced by oxidative stress.

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“…A direct correlation has been recognized between the progressive involvement of the neocortical areas and the increasing severity of dementia, suggesting that pathological tau proteins are reliable marker of the neurodegenerative process (Galluzzo et al, 2006;Buee et al, 2000). Memantine, a known neuro-receptor antagonist is currently used in the treatment of Alzheimer's disease.…”

Section: Introductionmentioning

confidence: 99%

Computational drug discovery of potential TAU protein kinase I inhibitors using in silico docking studies

Madeswaran¹,

Umamaheswari²,

Asokkumar³

et al. 2013

Bangladesh J Pharmacol

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The objective of the current study is to evaluate the tau protein kinase I inhibitory activity of flavonoids using in silico docking studies. In silico docking studies were carried out using AutoDock 4.2, based on the Lamarckian genetic algorithm principle. Memantine, a known neuro-receptor antagonist is currently used in the treatment of Alzheimer's disease. The results showed that all the selected flavonoids showed binding energy ranging between -7.07 kcal/mol to -4.85 kcal/mol when compared with that of the standard (-5.89 kcal/mol). Inhibition constant (6.62 µM to 280.05 µM) and intermolecular energy (-9.45 kcal/mol to -6.64 kcal/mol) of the ligands also coincide with the binding energy. These molecular docking analyses could lead to the further development of potent tau protein kinase I inhibitors for the treatment of Alzheimer's disease. Further investigations on the above compounds and in vivo studies are necessary to develop potential chemical entities for the prevention and treatment of Alzheimer's disease.

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Nutritional flavonoids impact on nuclear and extranuclear estrogen receptor activities

Cited by 49 publications

References 156 publications

Quantitative Proteomics and Transcriptomics Addressing the Estrogen Receptor Subtype-mediated Effects in T47D Breast Cancer Cells Exposed to the Phytoestrogen Genistein

Quantitative Proteomics and Transcriptomics Addressing the Estrogen Receptor Subtype-mediated Effects in T47D Breast Cancer Cells Exposed to the Phytoestrogen Genistein

Naringenin modulates skeletal muscle differentiation via estrogen receptor α and β signal pathway regulation

Computational drug discovery of potential TAU protein kinase I inhibitors using in silico docking studies

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