Abstract
Folate is a water-soluble B vitamin with a crucial role in the synthesis and methylation of DNA and in the metabolism of several amino acids. In the present study we investigated whether beverages like wine, beer and tea, or some of their specific constituents, affect the intestinal uptake of 3H-folic acid or 3H-methotrexate (an antifolate). All tested beverages significantly inhibited the uptake of 3H-folic acid by Caco-2 cells. Most of these beverages, with the exception of wines (not tested), also inhibited 3H-methotrexate uptake in these cells. Additionally, ethanol, when tested separately, inhibited the uptake of both compounds. Some of the tested phenolic compounds, namely myricetin, epigallocatechin gallate (EGCG) and isoxanthohumol, markedly inhibited 3H-folic acid uptake. Myricetin and EGCG also had a concentration-dependent inhibitory effect upon the uptake of 3H-methotrexate by Caco-2 cells. Resveratrol, quercetin and kaempferol were able to inhibit the transport of both compounds, but only in the concentration of 100 µM. In conclusion, dietary constituents may impact on intestinal folate uptake, as here shown for phenolic compounds.
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Abbreviations
- AfBeer:
-
Alcohol-free beer
- AfRW:
-
Alcohol-free red wine
- AfWW:
-
Alcohol-free white wine
- BT:
-
Black tea
- EGCG:
-
Epigallocatechin 3-gallate
- 3H-FA:
-
3H-folic acid
- GT:
-
Green tea
- Lbeer:
-
Lager beer
- OJ:
-
Orange juice
- 3H-MTX:
-
3H-methotrexate
- RFC:
-
Reduced folate carrier
- RW:
-
Red wine
- Sbeer:
-
Stout beer
- WW:
-
White wine
References
Stover PJ (2004) Physiology of folate and vitamin B12 in health and disease. Nutr Rev 62:S3–S12
Said HM (2004) Recent advances in carrier-mediated intestinal absorption of water-soluble vitamins. Annu Rev Physiol 66:419–446
Lucock M (2000) Folic acid: nutritional biochemistry, molecular biology, and role in disease processes. Mol Genet Metab 71:121–138
van der Put NM, van Straaten HW, Trijbels FJ, Blom HJ (2001) Folate, homocysteine and neural tube defects: an overview. Exp Biol Med (Maywood) 226:243–270
Ueland PM, Refsum H, Beresford SA, Vollset SE (2000) The controversy over homocysteine and cardiovascular risk. Am J Clin Nutr 72:324–332
Choi SW, Mason JB (2000) Folate and carcinogenesis: an integrated scheme. J Nutr 130:129–132
James SJ, Pogribna M, Pogribny IP, Melnyk S, Hine RJ, Gibson JB, Yi P, Tafoya DL, Swenson DH, Wilson VL, Gaylor DW (1999) Abnormal folate metabolism and mutation in the methylenetetrahydrofolate reductase gene may be maternal risk factors for Down syndrome. Am J Clin Nutr 70:495–501
Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM (1998) Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 55:1449–1455
Rots MG, Pieters R, Kaspers GJ, Veerman AJ, Peters GJ, Jansen G (2000) Classification of ex vivo methotrexate resistance in acute lymphoblastic and myeloid leukaemia. Br J Haematol 110:791–800
McGuire JJ (2003) Anticancer antifolates: current status and future directions. Curr Pharm Des 9:2593–2613
Dijkmans BA, Jansen G (2004) Antimetabolites in the treatment of arthritis: current status of the use of antimetabolites. Nucleosides Nucleotides Nucleic Acids 23:1083–1088
Peters GJ, Jansen G (1996) Resistance to Antimetabolites. In: Schilsky RL, Milano GA, Ratain MJ (eds) Principles of antineoplastic drug development and pharmacology. Marcel Dekker, New York, pp 543–585
Halsted CH, Villanueva JA, Devlin AM, Chandler CJ (2002) Metabolic interactions of alcohol and folate. J Nutr 132:2367S–2372S
Lieber CS (2000) ALCOHOL: its metabolism and interaction with nutrients. Annu Rev Nutr 20:395–430
Bode C, Bode JC (2003) Effect of alcohol consumption on the gut. Best Pract Res Clin Gastroenterol 17:575–592
Soleas GJ, Diamandis EP, Goldberg DM (1997) Wine as a biological fluid: history, production, and role in disease prevention. J Clin Lab Anal 11:287–313
Mukhtar H, Ahmad N (2000) Tea polyphenols: prevention of cancer and optimizing health. Am J Clin Nutr 71:1698S–1702S
van de Wiel A, van Golde PH, Hart HC (2001) Blessings of the grape. Eur J Intern Med 12:484–489
Yang CS, Maliakal P, Meng X (2002) Inhibition of carcinogenesis by tea. Annu Rev Pharmacol Toxicol 42:25–54
Middleton E Jr, Kandaswami C, Theoharides TC (2000) The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 52:673–751
Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA (2001) Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 74:418–425
Lemos C, Calhau C, Martel F, Azevedo I (2004) Intestinal thiamine uptake: characterization and nutritional modulation. FASEB J 18:A708
Selhub J, Rosenberg IH (1981) Folate transport in isolated brush border membrane vesicles from rat intestine. J Biol Chem 256:4489–4493
Said HM, Ghishan FK, Redha R (1987) Folate transport by human intestinal brush-border membrane vesicles. Am J Physiol 252:G229–G236
Said HM, Ma TY, Ortiz A, Tapia A, Valerio CK (1997) Intracellular regulation of intestinal folate uptake: studies with cultured IEC-6 epithelial cells. Am J Physiol 272:C729–C736
Martel F, Goncalves P, Azevedo I (2006) Absorption of folate by Caco-2 cells is not affected by high glucose concentration. Eur J Pharmacol 551:19–26
Subramanian VS, Chatterjee N, Said HM (2003) Folate uptake in the human intestine: promoter activity and effect of folate deficiency. J Cell Physiol 196:403–408
Delie F, Rubas W (1997) A human colonic cell line sharing similarities with enterocytes as a model to examine oral absorption: advantages and limitations of the Caco-2 model. Crit Rev Ther Drug Carrier Syst 14:221–286
Monteiro R, Calhau C, Martel F, Faria A, Mateus N, Azevedo I (2005) Modulation of MPP+ uptake by tea and some of its components in Caco-2 cells. Naunyn Schmiedebergs Arch Pharmacol 372:147–152
Monteiro R, Calhau C, Martel F, Guedes de Pinho P, Azevedo I (2005) Intestinal uptake of MPP+ is differently affected by red and white wine. Life Sci 76:2483–2496
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
Arnous A, Makris DP, Kefalas P (2001) Effect of principal polyphenolic components in relation to antioxidant characteristics of aged red wines. J Agric Food Chem 49:5736–5742
Said HM, Blair JA, Lucas ML, Hilburn ME (1986) Intestinal surface acid microclimate in vitro and in vivo in the rat. J Lab Clin Med 107:420–424
German JB, Walzem RL (2000) The health benefits of wine. Annu Rev Nutr 20:561–593
Sun AY, Simonyi A, Sun GY (2002) The “French Paradox” and beyond: neuroprotective effects of polyphenols. Free Radic Biol Med 32:314–318
Stevens JF, Page JE (2004) Xanthohumol and related prenylflavonoids from hops and beer: to your good health! Phytochemistry 65:1317–1330
Gerhauser C, Alt A, Heiss E, Gamal-Eldeen A, Klimo K, Knauft J, Neumann I, Scherf HR, Frank N, Bartsch H, Becker H (2002) Cancer chemopreventive activity of Xanthohumol, a natural product derived from hop. Mol Cancer Ther 1:959–969
Gerhauser C (2005) Beer constituents as potential cancer chemopreventive agents. Eur J Cancer 41:1941–1954
Gregory JF III (1997) Bioavailability of folate. Eur J Clin Nutr 51(Suppl 1):S54–S59
Lemos C, Azevedo I, Martel F (2005) Effect of red wine on the intestinal absorption of thiamine and folate in the rat: comparison with the effect of ethanol alone. Alcohol Clin Exp Res 29:664–671
Jansen G (1999) Receptor- and carrier-mediated transport systems for folates and antifolates: exploitation for folate-based chemotherapy and immunotherapy. In: Jackman AL (ed) Anticancer drug development guide: antifolate drugs in cancer therapy. Humana Press, Totowa, NJ, pp 293–321
Matherly LH, Goldman DI (2003) Membrane transport of folates. Vitam Horm 66:403–456
Chiao JH, Roy K, Tolner B, Yang CH, Sirotnak FM (1997) RFC-1 gene expression regulates folate absorption in mouse small intestine. J Biol Chem 272:11165–11170
Wang Y, Zhao R, Russell RG, Goldman ID (2001) Localization of the murine reduced folate carrier as assessed by immunohistochemical analysis. Biochim Biophys Acta 1513:49–54
Balamurugan K, Said HM (2006) Role of reduced folate carrier in intestinal folate uptake. Am J Physiol Cell Physiol 291:C189–C193
Sierra EE, Brigle KE, Spinella MJ, Goldman ID (1997) pH dependence of methotrexate transport by the reduced folate carrier and the folate receptor in L1210 leukemia cells. Further evidence for a third route mediated at low pH. Biochem Pharmacol 53:223–231
Acknowledgments
This work was supported by FCT (SFRH/BD/16883/2004), Programa Ciência, Tecnologia e Inovação do Quadro Comunitário de Apoio (POCTI/SAU-FCF/59382/2004) and iBeSa (Instituto de Bebidas e Saúde).
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Lemos, C., Peters, G.J., Jansen, G. et al. Modulation of folate uptake in cultured human colon adenocarcinoma Caco-2 cells by dietary compounds. Eur J Nutr 46, 329–336 (2007). https://doi.org/10.1007/s00394-007-0670-y
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DOI: https://doi.org/10.1007/s00394-007-0670-y