The Effect of Tomatine on Gene Expression and Cell Monolayer Integrity in Caco-2

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2018 Mar 14

PMID 29533987

Citations 5

Authors

Mattia P Arena

Coen Govers

Concetta Lotti

Luigi Ricciardi

Harry J Wichers

Jurriaan J Mes

Affiliations

Soon will be listed here.

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.

Citing Articles

Agri-Food Waste Recycling for Healthy Remedies: Biomedical Potential of Nutraceuticals from Unripe Tomatoes ( L.).

Piccolo V, Pastore A, Maisto M, Keivani N, Tenore G, Stornaiuolo M Foods. 2024; 13(2).

PMID: 38275698 PMC: 10815480. DOI: 10.3390/foods13020331.

Anticancer activity of glycoalkaloids from plants: A review.

Winkiel M, Chowanski S, Slocinska M Front Pharmacol. 2022; 13:979451.

PMID: 36569285 PMC: 9767987. DOI: 10.3389/fphar.2022.979451.

Scientometric and Methodological Analysis of the Recent Literature on the Health-Related Effects of Tomato and Tomato Products.

Tilesi F, Lombardi A, Mazzucato A Foods. 2021; 10(8).

PMID: 34441682 PMC: 8393598. DOI: 10.3390/foods10081905.

Risk assessment of glycoalkaloids in feed and food, in particular in potatoes and potato-derived products.

Schrenk D, Bignami M, Bodin L, Chipman J, Del Mazo J, Hogstrand C EFSA J. 2020; 18(8):e06222.

PMID: 32788943 PMC: 7417869. DOI: 10.2903/j.efsa.2020.6222.

Acute and Subacute Toxicity Profiles of the Methanol Extract of L. Leaves (Tomato), a Botanical with Promising Anticancer Potential.

Nguenang G, Ntyam A, Kuete V Evid Based Complement Alternat Med. 2020; 2020:8935897.

PMID: 32215048 PMC: 7077039. DOI: 10.1155/2020/8935897.

References

Takai T . TSLP expression: cellular sources, triggers, and regulatory mechanisms. Allergol Int. 2012; 61(1):3-17. DOI: 10.2332/allergolint.11-RAI-0395. View

Chiu F, Lin J . Tomatidine inhibits iNOS and COX-2 through suppression of NF-kappaB and JNK pathways in LPS-stimulated mouse macrophages. FEBS Lett. 2008; 582(16):2407-12. DOI: 10.1016/j.febslet.2008.05.049. View

Itkin M, Rogachev I, Alkan N, Rosenberg T, Malitsky S, Masini L . GLYCOALKALOID METABOLISM1 is required for steroidal alkaloid glycosylation and prevention of phytotoxicity in tomato. Plant Cell. 2011; 23(12):4507-25. PMC: 3269880. DOI: 10.1105/tpc.111.088732. View

Kozukue N, Han J, Lee K, Friedman M . Dehydrotomatine and alpha-tomatine content in tomato fruits and vegetative plant tissues. J Agric Food Chem. 2004; 52(7):2079-83. DOI: 10.1021/jf0306845. View

Ulluwishewa D, Anderson R, McNabb W, Moughan P, Wells J, Roy N . Regulation of tight junction permeability by intestinal bacteria and dietary components. J Nutr. 2011; 141(5):769-76. DOI: 10.3945/jn.110.135657. View

Kato A, Favoreto Jr S, Avila P, Schleimer R . TLR3- and Th2 cytokine-dependent production of thymic stromal lymphopoietin in human airway epithelial cells. J Immunol. 2007; 179(2):1080-7. PMC: 2220044. DOI: 10.4049/jimmunol.179.2.1080. View

Chow H, Hakim I, Vining D, Crowell J, Ranger-Moore J, Chew W . Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of Polyphenon E in healthy individuals. Clin Cancer Res. 2005; 11(12):4627-33. DOI: 10.1158/1078-0432.CCR-04-2549. View

Danis V, Franic G, Rathjen D, Brooks P . Effects of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-2, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-6 on the production of immunoreactive IL-1 and TNF-alpha by human monocytes. Clin Exp Immunol. 1991; 85(1):143-50. PMC: 1535710. DOI: 10.1111/j.1365-2249.1991.tb05695.x. View

Friedman M . Chemistry and anticarcinogenic mechanisms of glycoalkaloids produced by eggplants, potatoes, and tomatoes. J Agric Food Chem. 2015; 63(13):3323-37. DOI: 10.1021/acs.jafc.5b00818. View

10.

Vreeburg R, van Wezel E, Ocana-Calahorro F, Mes J . Apple extract induces increased epithelial resistance and claudin 4 expression in Caco-2 cells. J Sci Food Agric. 2011; 92(2):439-44. DOI: 10.1002/jsfa.4598. View

11.

Friedman M . Tomato glycoalkaloids: role in the plant and in the diet. J Agric Food Chem. 2002; 50(21):5751-80. DOI: 10.1021/jf020560c. View

12.

Jung H, Eckmann L, Yang S, Panja A, Fierer J, Kagnoff M . A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. J Clin Invest. 1995; 95(1):55-65. PMC: 295369. DOI: 10.1172/JCI117676. View

13.

Yamashoji S, Onoda E . Detoxification and function of immature tomato. Food Chem. 2016; 209:171-6. DOI: 10.1016/j.foodchem.2016.04.042. View

14.

Akbari P, Braber S, Alizadeh A, Verheijden K, Schoterman M, Kraneveld A . Galacto-oligosaccharides Protect the Intestinal Barrier by Maintaining the Tight Junction Network and Modulating the Inflammatory Responses after a Challenge with the Mycotoxin Deoxynivalenol in Human Caco-2 Cell Monolayers and B6C3F1 Mice. J Nutr. 2015; 145(7):1604-13. DOI: 10.3945/jn.114.209486. View

15.

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

16.

Heal K, Sheikh N, Hollingdale M, Morrow W, Taylor-Robinson A . Potentiation by a novel alkaloid glycoside adjuvant of a protective cytotoxic T cell immune response specific for a preerythrocytic malaria vaccine candidate antigen. Vaccine. 2001; 19(30):4153-61. DOI: 10.1016/s0264-410x(01)00166-9. View

17.

Langkilde S, Mandimika T, Schroder M, Meyer O, Slob W, Peijnenburg A . A 28-day repeat dose toxicity study of steroidal glycoalkaloids, alpha-solanine and alpha-chaconine in the Syrian Golden hamster. Food Chem Toxicol. 2009; 47(6):1099-108. DOI: 10.1016/j.fct.2009.01.045. View

18.

Hering N, Schulzke J . Therapeutic options to modulate barrier defects in inflammatory bowel disease. Dig Dis. 2009; 27(4):450-4. DOI: 10.1159/000233283. View

19.

Cheng L, Onisko B, Johnson E, Reader J, Griffey S, Larson A . Effects of purification on the bioavailability of botulinum neurotoxin type A. Toxicology. 2008; 249(2-3):123-9. DOI: 10.1016/j.tox.2008.04.018. View

20.

Sims J, Smith D . The IL-1 family: regulators of immunity. Nat Rev Immunol. 2010; 10(2):89-102. DOI: 10.1038/nri2691. View