Transport of resveratrol, a cancer chemopreventive agent, to cellular targets: plasmatic protein binding and cell uptake

Jannin, Brigitte; Menzel, Matthias; Berlot, Jean-Pierre; Delmas, Dominique; Lançon, Allan; Latruffe, Norbert

doi:10.1016/j.bcp.2004.04.028

Cited by 159 publications

(122 citation statements)

References 27 publications

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“…The present study shows that resveratrol, which binds serum proteins such as albumin (26), can enter the cells through both a passive diffusion and a carrier-facilitated and monensin-sensitive process. Resveratrol accumulates in DRMs known as lipid rafts and promotes the redistribution of various protein kinases as well as components of the integrin signaling complex in these membrane fractions.…”

Section: Discussionmentioning

confidence: 71%

Endocytosis of Resveratrol via Lipid Rafts and Activation of Downstream Signaling Pathways in Cancer Cells

Colin

Limagne²,

Jeanningros³

et al. 2011

Cancer Prevention Research

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trans-Resveratrol has been proposed to prevent tumor growth and to sensitize cancer cells to anticancer agents. Polyphenol entry into the cells has remained poorly understood. Here, we show that [ 3 H]-resveratrol enters colon cancer cells (SW480, SW620, HT29) and leukemia U937 cells through a monensin (5-20 mmol/L) -sensitive process that suggests clathrin-independent endocytosis. Uptake of the molecule can be prevented by methyl-b-cyclodextrin (2-12 mg/mL), nystatin (12 ng/mL), and filipin (1 mg/mL), which all disrupt plasma membrane lipid rafts. Accordingly, radiolabeled resveratrol accumulates in sphingomyelin-and cholesterol-enriched cell fractions. Interestingly, extracellular signalregulated kinases (ERK), c-Jun NH 2 -terminal kinases (JNK), and Akt also accumulate in lipid rafts on resveratrol exposure (IC 50 at 48 h % 30 mmol/L in SW480 and U937 cells). In these rafts also, resveratrol promotes the recruitment, by the integrin a V b 3 (revealed by coimmunoprecipitation with an anti-integrin a V b 3 antibody), of signaling molecules that include the FAK (focal adhesion kinase), Fyn, Grb2, Ras, and SOS proteins. Resveratrol-induced activation of downstream signaling pathways and caspase-dependent apoptosis is prevented by endocytosis inhibitors, lipid raft-disrupting molecules, and the integrin antagonist peptide arginine-glycine-aspartate (500 nmol/L). Altogether, these data show the role played by lipid rafts in resveratrol endocytosis and activation of downstream pathways leading to cell death.

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Section: Discussionmentioning

confidence: 71%

Endocytosis of Resveratrol via Lipid Rafts and Activation of Downstream Signaling Pathways in Cancer Cells

Colin

Limagne²,

Jeanningros³

et al. 2011

Cancer Prevention Research

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“…This suggested that the administration of a combination of the aglycone (RSV) and its glycosylated derivative may produce a long-lasting increase in circulating levels of the polyphenols and its metabolites. RSV interacts with a high affinity with albumin and this binding may have a crucial role in improving the distribution of RSV in different body tissues and organs (70). The adsorption and distribution of RSV in organs such as the heart, liver and kidney following oral administration were described for the first time in 1996, by sub-ministration of a daily dose of 6.5 mg/l resveratrol to two different groups of rats (73), and have more recently been confirmed (in the liver, IC50 for the inhibition of resveratrol sulphation was 12±2 pM quercetin, 1.0±0.04 µM fisetin, 1.4±0.1 µM myricetin, 2.2±0.1 µM kaempferol and 2.8±0.2 µM apigenin) (74,75) and extended to the bile, stomach and duodenum (76).…”

Section: Bioavailability and Pharmacokineticsmentioning

confidence: 99%

Resveratrol (3,5,4′-trihydroxystilbene) and its properties in oral diseases

Perrone

Fuggetta

Ardito

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Health promotion strategies and lifestyle changes are important in disease prevention. Oral health has received a large amount of attention previously as it is a fundamental component of general health and it contributes to the quality of life. Therefore, the study of associations between diet, health and the presence of bioactive compounds in food is receiving a substantial amount of attention. In the present review the effects and targets of a natural polyohenolic stilbenoid compound; resveratrol (3,5,4'-trihydroxystilbene; RSV) is assessed, and the future prospects for RSV in promoting oral health are considered. RSV is a phytoalexin, synthesized by a wide range of plants and abundantly extracted in grape skin, it has been purported to exert a multiplicity of anti-inflammatory, anti-viral, anti-microbial, estrogenic, anticancer, cardioprotective, neuroprotective and immunomodulatory functions. In this review, following an introduction documenting the biochemistry of RSV and RSV glucosides, the bioavailability and pharmacokinetics of RSV are described. Considering its multiple properties, the present review has focused on the potential benefits of RSV as an antioxidant and chemopreventive agent.

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“…RSV has poor water solubility and thus has to be bound to plasma proteins to assure its body distribution and bioavailability [66]. Indeed, in its transport, RSV can bind to serum proteins [67] such as lipoproteins, hemoglobin, and albumin which facilitate its carrier mediated cellular uptake and then it can passively diffuse through the plasma membrane [68,69] investigated the binding properties of RSV to plasma proteins, such as human serum albumin (HSA) and hemoglobin (Hb) and confirmed that both complexes formed are spontaneous and exothermic. The binding constant of RSV-HSA complex is larger than that of RSV-Hb, which indicates the higher affinity of HSA to RSV.…”

Section: Distributionmentioning

confidence: 99%

Reduction of Hepatotoxicity Induced by Doxorubicin

Bengaied¹,

Ribeiro²,

Amri³

et al. 2017

J Integr Oncol

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Doxorubicin (DOX) has been used in the treatment of variety of cancers but its administration is limited by a dosedependent toxicity. Its cytotoxic effects on malignant cells have shown an increase in the risk of cardiotoxicity, hepatoxicity, renal insufisance.Antioxydants have been explored for both their cancer preventive properties and chemodulatory of DOX toxicity. Resveratrol (RSV) is a polyphenolic constituent of several dietary mainly of grapes and wine origin recently its anticancer potential has been extensively explored, revealing its anti-proliferative effect on different cancer cell lines, both in vitro and in vivo. RSV is also known to have modulatory effects on cell apoptosis, migration and growth via various signaling pathways. Though, RSV possesses great medicinal value, its applications as a therapeutic drug is limited. Problems like low oral bioavailability and poor aqueous solubility make RSV an unreliable candidate for therapeutic purposes. Additionally, the rapid gastrointestinal digestion of RSV is also a major barrier for its clinical translation. Hence, to overcome these disadvantages RSV-based nanodelivery systems have been considered in recent times. Nanodelivery systems of RSV have shown promising results in its uptake by the epithelial system as well as enhanced delivery to the target site. Herein we have tried to bring new new insights into the molecular mechanisms of DOX toxicity with respect to DNA damage, free radicals and whether RSV can be a playmaker as chemodulatory of DO x .

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Transport of resveratrol, a cancer chemopreventive agent, to cellular targets: plasmatic protein binding and cell uptake

Cited by 159 publications

References 27 publications

Endocytosis of Resveratrol via Lipid Rafts and Activation of Downstream Signaling Pathways in Cancer Cells

Endocytosis of Resveratrol via Lipid Rafts and Activation of Downstream Signaling Pathways in Cancer Cells

Resveratrol (3,5,4′-trihydroxystilbene) and its properties in oral diseases

Reduction of Hepatotoxicity Induced by Doxorubicin

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