Purple Waxy Corn Modifies the Expression of CYP3A4, N-acetyltransferase 2, and UGT1A6 in HepG2 and Caco-2 Cells
doi.org/10.26538/tjnpr/v5i8.21
Keywords:
Zea mays, CYP3A4, NAT2, UGT1A6, Food Drug InteractionAbstract
Purple waxy corn (Zea mays L. var. ceritina Kulesh.), or black purple sticky corn, is an edible plant with antioxidant properties according to its rich anthocyanin, phenolic and flavonoid content. This study aimed to determine how purple waxy corn modified drug metabolizing genes (CYP1A2, CYP2C9, CYP3A4, UGT1A6, and NAT2) and a drug transporter (OATP1B1) in human hepatocellular carcinoma (HepG2) and colorectal adenocarcinoma (Caco-2) cells. The cells were incubated with purple waxy corn (125 to 1,000 µg/mL) for 48 h. Cell viability, reactive oxygen species (ROS), aspartate transaminase (AST), and alanine aminotransferase (ALT) levels were investigated. The mRNA expression of target genes was determined by RT/qPCR. Cell viability remained above 80% even at the maximum tested concentration of purple waxy corn (1,000 µg/mL). Expression of CYP1A2 and CYP2C9 was not modified by purple waxy corn in either HepG2 or Caco-2 cells, but CYP3A4 expression was significantly suppressed in Caco-2 cells. At the highest concentration (1,000 µg/mL), purple waxy corn markedly induced expression of UGT1A6 and NAT2 mRNA in Caco-2 cells. Conversely, purple waxy corn suppressed expression of NAT2 at the highest concentration in HepG2 cells. The expression of OATP1B1 was not affected by purple waxy corn in either cell type. Therefore, consumption of large amounts purple waxy corn could cause food-drug interaction via differential modification of CYP3A4, UGT1A6, and NAT2.
References
Pedreschi R and Cisneros-Zevallos L. Phenolic profiles of Andean purple corn (Zea mays L.). Food Chem. 2007; 100(3):956-963.
Kirisattayakul W, Wattanathorn J, Iamsaard S, Jittiwat J, Suriharn B, Lertrat K. Neuroprotective and memoryenhancing effect of the combined extract of purple waxy corn cob and pandan in ovariectomized rats. Oxid Med Cell Longev. 2017; 2017(1):5187102.
Kapcum C, Uriyapongson S, Uriyapongson J. Phenolics, anthocyanins and antioxidant activities in waste products from different parts of purple waxy corn (Zea mays L.). Songklanakarin J Sci Technol. 2021; 3(2):398-405.
Thiraphatthanavong P, Wattanathorn J, Muchimapura S, Thukham-Mee W, Wannanon P, Tong-Un T, Suriharn B, Lertrat K. Preventive effect of Zea mays L. (purple waxy corn) on experimental diabetic cataract. Biomed Res Int. 2014; 2014(1):507435.
Thiraphatthanavong P, Wattanathorn J, Muchimapura S, Thukham-mee W, Lertrat K, Suriharn B. The combined extract of purple waxy corn and ginger prevents cataractogenesis and retinopathy in streptozotocin-diabetic rats. Oxid Med Cell Longev. 2014; 2014(1):789406.
Orellana-Paucar A and Vintimilla-Rojas D. Interactions of clinical relevance associated with concurrent administration of prescription drug and food or medicinal plants: a systematic review protocol. Syst Rev. 2020; 9(1):1-6.
Zanger UM and Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 2013; 138(1):103-141.
Kim SB, Kim KS, Kim DD, Yoon IS. Metabolic interactions of rosmarinic acid with human cytochrome
P450 monooxygenases and uridine diphosphate glucuronosyltransferases. Biomed Pharmacother. 2019;
(1):111-117.
Salazar-González RA, Turiján-Espinoza E, Hein DW, Milán-Segovia RC, Uresti-Rivera EE, Portales-Pérez DP.
Expression and genotype-dependent catalytic activity of Nacetyltransferase 2 (NAT2) in human peripheral blood mononuclear cells and its modulation by Sirtuin 1. Biochem Pharmacol. 2018; 156(1):340-347.
Lněničková K, Šadibolová M, Matoušková P, Szotáková B, Skálová L, Boušová I. The modulation of phase II drugmetabolizing enzymes in proliferating and differentiated CaCo-2 cells by hop-derived prenylflavonoids. Nutrients. 2020; 12(7):1238.
Kim SB, Yoon IS, Kim KS, Cho SJ, Kim YS, Cho HJ, Chung SJ, Chong S, Kim DD. In vitro and in vivo
evaluation of the effect of puerarin on hepatic cytochrome p450-mediated drug metabolism. Planta Med. 2014; 80(07):561-567.
Kayesh R, Farasyn T, Crowe A, Liu Q, Pahwa S, Alam K, Neuhoff S, Hatley O, Ding K, Yue W. Assessing
OATP1B1- and OATP1B3-mediated drug-drug interaction potential of vemurafenib using R-value and physiologicall-based pharmacokinetic models. J Pharm Sci. 2021; 110(1):314-324.
Chen L, Liu L, Chen Y, Liu M, Xiong Y, Zhang H, Huang S, Xia C. Modulation of transporter activity of OATP1B1 and OATP1B3 by the major active components of Radix Ophiopogonis. Xenobiotica. 2019; 49(10) 1221-1218.
Kafle A, Mohapatra SS, Sarma J, Reddy I. Food-drug interaction: a review. Pharma Innov. 2018; 7(1) 114-118.
Kuno N and Mizutani T. Influence of synthetic and natural food dyes on activities of CYP2A6, UGT1A6, and
UGT2B7. J Toxicol Environ Heal Part A. 2005; 68(16):1431-1444.
Niu N and Wang L. In vitro human cell line models to predict clinical response to anticancer drugs.
Pharmacogenomics. 2015; 16(3):273-285.
Vaessen SFC, van Lipzig MMH, Pieters RHH, Krul CAM, Wortelboer HM, van de Steeg E. Regional xpression levels of drug transporters and metabolizing enzymes along the pig and human intestinal tract and comparison with Caco-2 cells. Drug Metab Dispos. 2017; 45(4):353-360.
Iftikhar M, Iftikhar A, Zhang H, Gong L, Wang J. Transport, metabolism and remedial potential of functional food extracts (FFEs) in Caco-2 cells monolayer: a review. Food Res Int. 2020; 136(1):109240.
Sriset Y, Chatuphonprasert W, Jarukamjorn K. Bergenin attenuates sodium selenite-induced hepatotoxicity via improvement of hepatic oxidant-antioxidant balance in HepG2 cells and ICR mice. J Biol Act Prod from Nat. 2021; 11(2):97-115.
Sriset Y, Chatuphonprasert W, Jarukamjorn K. In vitro antioxidant potential of Mallotus repandus (Willd.) Muell. Arg stem extract and its active constituent bergenin. Songklanakarin J Sci Technol. 2021; 43(1):24-30.
Chatuphonprasert W, Kitisripanya T, Putalun W, Ellinger I, Jarukamjorn K. Pueraria candollei var. mirifica-induced CYP1A1 and CYP1A2 expression in human choriocarcinoma bewo cells. Pharmacogn Mag. 2020;
(5): 506.
Miret S, De Groene EM, Klaffke W. Comparison of in vitro assays of cellular toxicity in the human hepatic cell line HepG2. J Biomol Screen. 2006; 11(2):184-193.
Singto T, Tassaneeyakul W, Porasuphatana S, Protective effects of purple waxy corn on aflatoxin b1-induced oxidative stress and micronucleus in HepG2 cells. Indian J Pharm Sci. 2020; 82(3):506-513.
Novotna A, Korhonova M, Bartonkova I, Soshilov AA, Denison MS, Bogdanova K, Kolar M, Bednar P, Dvorak Z. Enantiospecific effects of ketoconazole on aryl hydrocarbon receptor. PLoS One. 2014; 9(7):e101832.
Usui T, Saitoh Y, Komada F, Induction of CYP3As in HepG2 cells by several drugs-Association between
induction of CYP3A4 and expression of glucocorticoid receptor. Biol Pharm Bull. 2003; 26(4):510-517.
Nikulin SV, Tonevitsky EA, Poloznikov AA. Effect of ketoconazole on the transport and metabolism of drugs in the human liver cell model. Russ Chem Bull. 2017; 66(1):150-155.
Zhou SF, Wang B, Yang LP, Liu JP. Structure, function, regulation and polymorphism and the clinical significance of human cytochrome P450 1A2. Drug Metab Rev. 2010; 42(2): 268-354.
Miners JO and Birkett DJ. Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. Br J Clin Pharmacol. 1998; 45(6): 525-538.
Drozdzik M, Busch D, Lapczuk J, Müller J, Ostrowski M, Kurzawski M, Oswald S. Protein abundance of clinically relevant drug-metabolizing enzymes in the human liver and intestine: a comparative analysis in paired tissue specimens. Clin Pharmacol Ther. 2018; 104(3):515-524.
Bièche I, Narjoz C, Asselah T, Vacher S, Marcellin P, Lidereau R, Beaune P, de Waziers I. Reverse transcriptase-PCR quantification of mRNA levels from cytochrome (CYP)1, CYP2 and CYP3 families in 22 different human tissues. Pharmacogenet Genomics. 2007; 17(9):371-342.
Bock KW, Eckle T, Ouzzine M, Fournel-Gigleux S. Coordinate induction by antioxidants of UDP-glucuronosyltransferase UGT1A6 and the apical conjugate export pump MRP2 (multidrug resistance protein 2) in Caco-2 cells. Biochem Pharmacol. 2000; 59(5):467-470.
Husain A, Zhang X, Doll MA, States JC, Barker DF, Hein DW. Identification of N-acetyltransferase 2 (NAT2)
transcription start sites and quantitation of NAT2-specific mRNA in human tissues. Drug Metab Dispos. 2007; 35(5): 721-727.
Hein DW. Molecular genetics and function of NAT1 and NAT2: role in aromatic amine metabolism and
carcinogenesis. Mutat Res Mol Mech Mutagen. 2002; 506(1):65-77.
Chen Y, Xiao P, Ou‐Yang DS, Fan L, Guo D, Wang YN, Han Y, Tu JH, Zhou G, Huang YF, Zhou HH. Simultaneous action of the flavonoid quercetin on cytochrome P450 (CYP) 1A2, CYP2A6, N-acetyltransferase and xanthine oxidase activity in healthy volunteers. Clin Exp Pharmacol Physiol. 2009; 36(8):828-833.
Maubon N, Le Vee M, Fossati L, Audry M, Le Ferrec E, Bolze S, Fardel O. Analysis of drug transporter expression in human intestinal Caco-2 cells by real-time PCR. Fundam Clin Pharmacol. 2007; 21(6):659-663.
Wang L and Sweet DH. Potential for food-drug interactions by dietary phenolic acids on human organic anion transporters 1 (SLC22A6), 3 (SLC22A8), and 4 (SLC22A11). Biochem Pharmacol. 2012; 84(8):1088-1095.
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
