The Effect of Tomatine on Gene Expression and Cell Monolayer Integrity in Caco-2
More understanding of the risk-benefit effect of the glycoalkaloid tomatine is required to be able to estimate the role it might play in our diet. In this work, we focused on effects towards intestinal epithelial cells based on a Caco-2 model in order to analyze the influence on the cell monolayer i...
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Published in | Molecules (Basel, Switzerland) Vol. 23; no. 3; p. 644 |
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Abstract | More understanding of the risk-benefit effect of the glycoalkaloid tomatine is required to be able to estimate the role it might play in our diet. In this work, we focused on effects towards intestinal epithelial cells based on a Caco-2 model in order to analyze the influence on the cell monolayer integrity and on the expression levels of genes involved in cholesterol/sterol biosynthesis (LDLR), lipid metabolism (NR2F2), glucose and amino acid uptake (SGLT1, PAT1), cell cycle (PCNA, CDKN1A), apoptosis (CASP-3, BMF, KLF6), tight junctions (CLDN4, OCLN2) and cytokine-mediated signaling (IL-8, IL1β, TSLP, TNF-α). Furthermore, since the bioactivity of the compound might vary in the presence of a food matrix and following digestion, the influence of both pure tomatine and in vitro digested tomatine with and without tomato fruit matrix was studied. The obtained results suggested that concentrations <20 µg/mL of tomatine, either undigested or in vitro digested, do not compromise the viability of Caco-2 cells and stimulate cytokine expression. This effect of tomatine, in vitro digested tomatine or in vitro digested tomatine with tomato matrix differs slightly, probably due to variations of bioactivity or bioavailability of the tomatine. The results lead to the hypothesis that tomatine acts as hormetic compound that can induce beneficial or risk toxic effects whether used in low or high dose. |
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AbstractList | More understanding of the risk-benefit effect of the glycoalkaloid tomatine is required to be able to estimate the role it might play in our diet. In this work, we focused on effects towards intestinal epithelial cells based on a Caco-2 model in order to analyze the influence on the cell monolayer integrity and on the expression levels of genes involved in cholesterol/sterol biosynthesis (LDLR), lipid metabolism (NR2F2), glucose and amino acid uptake (SGLT1, PAT1), cell cycle (PCNA, CDKN1A), apoptosis (CASP-3, BMF, KLF6), tight junctions (CLDN4, OCLN2) and cytokine-mediated signaling (IL-8, IL1β, TSLP, TNF-α). Furthermore, since the bioactivity of the compound might vary in the presence of a food matrix and following digestion, the influence of both pure tomatine and in vitro digested tomatine with and without tomato fruit matrix was studied. The obtained results suggested that concentrations <20 µg/mL of tomatine, either undigested or in vitro digested, do not compromise the viability of Caco-2 cells and stimulate cytokine expression. This effect of tomatine, in vitro digested tomatine or in vitro digested tomatine with tomato matrix differs slightly, probably due to variations of bioactivity or bioavailability of the tomatine. The results lead to the hypothesis that tomatine acts as hormetic compound that can induce beneficial or risk toxic effects whether used in low or high dose. |
Author | Wichers, Harry J Mes, Jurriaan J Govers, Coen Ricciardi, Luigi Arena, Mattia P Lotti, Concetta |
AuthorAffiliation | 4 Laboratory of Food Chemistry, Wageningen University and Research Centre, Bomenweg 2, P.O. Box 8129, 6700 EV Wageningen, The Netherlands 2 Wageningen Food & Biobased Research, Wageningen University and Research, Bornse Weilanden 9, P.O. Box 17, 6700 AA Wageningen, The Netherlands; coen.govers@wur.nl (C.G.); harry.wichers@wur.nl (H.J.W.); jurriaan.mes@wur.nl (J.J.M.) 3 Department of Soil, Plant and Food Sciences, Plant Genetics and Breeding Unit; Via Amendola 165/A, 70125 Bari, Italy; luigi.ricciardi@uniba.it 1 Department of the Sciences of Agriculture, Food and Environment, University of Foggia, Via Napoli 25, 71122 Foggia, Italy; mattiapia.arena@unifg.it |
AuthorAffiliation_xml | – name: 2 Wageningen Food & Biobased Research, Wageningen University and Research, Bornse Weilanden 9, P.O. Box 17, 6700 AA Wageningen, The Netherlands; coen.govers@wur.nl (C.G.); harry.wichers@wur.nl (H.J.W.); jurriaan.mes@wur.nl (J.J.M.) – name: 1 Department of the Sciences of Agriculture, Food and Environment, University of Foggia, Via Napoli 25, 71122 Foggia, Italy; mattiapia.arena@unifg.it – name: 4 Laboratory of Food Chemistry, Wageningen University and Research Centre, Bomenweg 2, P.O. Box 8129, 6700 EV Wageningen, The Netherlands – name: 3 Department of Soil, Plant and Food Sciences, Plant Genetics and Breeding Unit; Via Amendola 165/A, 70125 Bari, Italy; luigi.ricciardi@uniba.it |
Author_xml | – sequence: 1 givenname: Mattia P orcidid: 0000-0002-0627-6214 surname: Arena fullname: Arena, Mattia P email: mattiapia.arena@unifg.it, mattiapia.arena@unifg.it organization: Wageningen Food & Biobased Research, Wageningen University and Research, Bornse Weilanden 9, P.O. Box 17, 6700 AA Wageningen, The Netherlands. mattiapia.arena@unifg.it – sequence: 2 givenname: Coen surname: Govers fullname: Govers, Coen email: coen.govers@wur.nl organization: Wageningen Food & Biobased Research, Wageningen University and Research, Bornse Weilanden 9, P.O. Box 17, 6700 AA Wageningen, The Netherlands. coen.govers@wur.nl – sequence: 3 givenname: Concetta surname: Lotti fullname: Lotti, Concetta email: concetta.lotti@unifg.it organization: Department of the Sciences of Agriculture, Food and Environment, University of Foggia, Via Napoli 25, 71122 Foggia, Italy. concetta.lotti@unifg.it – sequence: 4 givenname: Luigi surname: Ricciardi fullname: Ricciardi, Luigi email: luigi.ricciardi@uniba.it organization: Department of Soil, Plant and Food Sciences, Plant Genetics and Breeding Unit; Via Amendola 165/A, 70125 Bari, Italy. luigi.ricciardi@uniba.it – sequence: 5 givenname: Harry J surname: Wichers fullname: Wichers, Harry J email: harry.wichers@wur.nl, harry.wichers@wur.nl organization: Laboratory of Food Chemistry, Wageningen University and Research Centre, Bomenweg 2, P.O. Box 8129, 6700 EV Wageningen, The Netherlands. harry.wichers@wur.nl – sequence: 6 givenname: Jurriaan J surname: Mes fullname: Mes, Jurriaan J email: jurriaan.mes@wur.nl organization: Wageningen Food & Biobased Research, Wageningen University and Research, Bornse Weilanden 9, P.O. Box 17, 6700 AA Wageningen, The Netherlands. jurriaan.mes@wur.nl |
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Keywords | glycoalkaloid immune system tomatine qPCR gene expression gut |
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SubjectTerms | Apoptosis Bioavailability Biocompatibility Biological activity Biosynthesis Cell cycle Cholesterol Consumer Science & Health Cytokines Epithelial cells FBR Consumer Science & Health Food matrix Food, Health & Consumer Research Gene expression Glucose metabolism glycoalkaloid gut immune system Interleukin 1 Interleukin 8 Intestine Lipid metabolism Metabolism Monolayers Proliferating cell nuclear antigen qPCR Thymic stromal lymphopoietin Tight junctions Tomatine Tomatoes Toxicity Tumor necrosis factor-α Viability VLAG |
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Title | The Effect of Tomatine on Gene Expression and Cell Monolayer Integrity in Caco-2 |
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