The activation of the Nrf2/ARE pathway in HepG2 hepatoma cells by phytochemicals and subsequent modulation of phase II and antioxidant enzyme expression

Journal of Physiology and Biochemistry

Volumn 71, Issue 2, 2015, Pages 227-238

  Krajka Kuźniak, Violetta ^a   Paluszczak, Jarosław ^a   Szaefer, Hanna ^a   Baer Dubowska, Wanda ^a  

^a POZNAN UNIVERSITY OF MEDICAL SCIENCES   (Poland)

Author keywords

Antioxidant and phase II enzymes; HepG2; Indole 3 carbinol; Nrf2; Phenethyl isothiocyanate; Protocatechuic and tannic acids

Indexed keywords

ANTIOXIDANT; ENZYME; HYDROXYBENZOIC ACID DERIVATIVE; INDOLE DERIVATIVE; INDOLE-3-CARBINOL; ISOTHIOCYANIC ACID DERIVATIVE; NFE2L2 PROTEIN, HUMAN; PHENETHYL ISOTHIOCYANATE; PLANT MEDICINAL PRODUCT; PROTOCATECHUIC ACID; TANNIN DERIVATIVE; TRANSCRIPTION FACTOR NRF2;

ANTIOXIDANT RESPONSIVE ELEMENT; CELL SURVIVAL; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; HEPG2 CELL LINE; HUMAN; METABOLISM; PHOSPHORYLATION; SIGNAL TRANSDUCTION;

ANTIOXIDANT RESPONSE ELEMENTS; ANTIOXIDANTS; CELL SURVIVAL; ENZYMES; GENE EXPRESSION REGULATION; HEP G2 CELLS; HUMANS; HYDROXYBENZOATES; INDOLES; ISOTHIOCYANATES; NF-E2-RELATED FACTOR 2; PHOSPHORYLATION; PHYTOCHEMICALS; SIGNAL TRANSDUCTION; TANNINS;

EID: 84939984048     PISSN: 11387548     EISSN: 18778755     Source Type: Journal    
DOI: 10.1007/s13105-015-0401-4     Document Type: Article

References (40)

1. Alia M, Ramos S, Mateos R, Granado-Serrano AB, Bravo L, Goya L (2006) Quercetin protects human hepatoma HepG2 against oxidative stress induced by tert-butyl hydroperoxide. Toxicol Appl Pharmacol 212:110–118
2. Carbonaro M, Grant G, Pusztai A (2001) Evaluation of polyphenol bioavalability in rat small intestine. Eur J Nutr 40:84–90
3. Giudice A, Montella M (2006) Activation of the Nrf2-ARE signaling pathway: a promising strategy in cancer prevention. Bioessays 28:169–181
4. Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, Oyake T, Hayashi N, Satoh K, Hatayama I, Yamamoto M, Nabeshima Y (1997) An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 236:313–322
5. Jaiswal AK (2004) Nrf2 signaling in coordinated activation of antioxidant gene expression. Free Radic Biol Med 36:1199–1207
6. Jeong WS, Keum YS, Chen C, Jain MR, Shen G, Kim JH, Li W, Kong AN (2005) Differential expression and stability of endogenous nuclear factor E2-related factor 2 (Nrf2) by natural chemopreventive compounds in HepG2 human hepatoma cells. J Bioch Mol Biol 38:167–176
7. Keum YS, Owuor ED, Kim BR, Hu R, Kong AN (2003) Involvement of Nrf2 and JNK1 in the activation of antioxidant responsive element (ARE) by chemopreventive agent phenethyl isothiocyanate (PEITC). Pharm Res 20:1351–1356
8. Krajka-Kuźniak V, Kaczmarek J, Baer-Dubowska W (2008) Effect of naturally occurring phenolic acids on the expression of glutathione S-transferase isozymes in the rat. Food Chem Toxicol 46:1097–1102
9. Krajka-Kuźniak V, Paluszczak J, Baer-Dubowska W (2013) Xanthohumol induces phase II enzymes via Nrf2 in human hepatocytes in vitro. Toxicol In Vitro 27:149–156
10. Krajka-Kuźniak V, Szaefer H, Bartoszek A, Baer-Dubowska W (2011) Modulation of rat hepatic and kidney phase II enzymes by cabbage juices: comparison with the effects of indole-3-carbinol and phenethyl isothiocyanate. Br J Nutr 105:816–826
11. Krajka-Kuźniak V, Szaefer H, Baer-Dubowska W (2004) Modulation of 3-methylcholantrene-induced rat hepatic and renal cytochrome P450 and phase II enzymes by plant phenols: protocatechuic and tannic acids. Toxicol Lett 152:117–126
12. Krajka-Kuźniak V, Szaefer H, Baer-Dubowska W (2005) Modulation of cytochrome P450 and phase II enzymes by protocatechuic acid in mouse liver and kidney. Toxicology 216:24–31
13. Krajka-Kuźniak V, Szaefer H, Baer-Dubowska W (2008) Hepatic and extrahepatic expression of glutathione S-transferase isozymes in mice and its modulation by naturally occurring phenolic acids. Environ Toxicol Pharmacol 25:27–32
14. Kwak MK, Wakabayashi N, Kensler TW (2004) Chemoprevention through the Keap1-Nrf2 signaling pathway by phase 2 enzyme inducers. Mutat Res 555:133–148
15. La Marca M, Beffy P, Della Croce C, Gervasi PG, Iori R, Puccinelli E, Longo V (2012) Structural influence of isothiocyanates on expression of cytochrome P450 phase II enzymes, and activation of Nrf2 in primary rat hepatocytes. Food Chem Toxicol 50:2822–2830
16. Landi S (2000) Mammalian class theta GST and differential susceptibility to carcinogens: a review. Mutat Res 463:247–283
17. Lee JS, Surh YJ (2005) Nrf2 as a novel molecular target for chemoprevention. Cancer Lett 224:171–184
18. Liebes L, Conaway CC, Hochster H, Mendoza S, Hecht SS, Crowell J, Chung FL (2001) High-performance liquid chromatography-based determination of total isothiocyanate levels in human plasma: application to studies with 2-phenethyl isothiocyanate. Anal Biochem 291:279–289
19. Lo HW, Ali-Osman F (2007) Genetic polymorphism and function of glutathione S-transferases in tumor drug resistance. Curr Opin Pharmacol 7:367–374
20. Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
21. Matés JM, Pérez-Gómez C, Núñez de Castro I (1999) Antioxidant enzymes and human diseases. Clin Biochem 32:595–603
22. McKay DL, Chen CY, Zampariello CA, Blumberg JB (2015) Flavonoids and phenolics from cranberry juice are bioavailable and bioactive in healthy older adults. Food Chem 168:233–240
23. Moiseeva EP, Almeida GA, Jones GDD, Manson MM (2007) Extended treatment with physiologic concentrations of dietary phytochemicals results in altered gene expression, reduced growth, and apoptosis of cancer cells. Mol Cancer Ther 6:3071–3079
24. NakamuraY TS, Tonogai Y (2003) Method for analysis of tannic acid and its metabolites in biological samples: application to tannic acid metabolism in the rat. J Agric Food Chem 51:331–339
25. Nam S, Smith DM, Dou QP (2001) Tannic acid potently inhibit tumor cell proteasome activity increases p27 and Bax expression, and induces G1 arrest and apoptosis. Cancer Epidemiol Biomarkers Prev 10:1083–1088
26. Nguyen T, Sherrat PJ, Pickett CB (2003) Regulatory mechanisms controlling gene expression mediated by the antioxidant response element. Annu Rev Pharmacol Toxicol 43:233–260
27. Pi J, Bai Y, Reece JM, Williams J, Liu D, Freeman ML, Fahl WE, Shugar D, Liu J, Qu W, Waalkes MP (2007) Molecular mechanism of human Nrf2 activation and degradation: role of sequential phosphorylation by protein kinase CK2. Free Rad Biol Med 15:1797–1806
28. Saw CL, Cintrón M, Wu TY, Guo Y, Huang Y, Jeong WS, Kong AN (2011) Pharmacodynamics of dietary phytochemical indoles I3C and DIM: induction of Nrf2-mediated phase II drug metabolizing and antioxidant genes and synergism with isothiocyanates. Biopharm Drug Dispos 32:289–300
29. Saw CLL, Kong A-NT (2011) Nuclear factor-erythroid 2-related factor 2 as a chemopreventive target in colorectal cancer. Exp Opin Therap Targets 15:281–295
30. Suhr Y-J, Kundu JK, Na H-K (2008) Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals. Planta Med 74:1526–1539
31. Talalay P (2000) Chemoprotection against cancer by induction of phase 2 enzymes. Biofactors 12:5–11
32. Talalay P, Dinkova-Kostova AT, Holtzclaw WD (2003) Importance of phase 2 gene regulation in protection against electrophile and reactive oxygen toxicity and carcinogenesis. Advan Enzyme Reg 43:121–134
33. Westerink WM, Schoonen WG (2007) Phase II enzyme levels in HepG2 cells and cryopreserved primary human hepatocytes and their induction in HepG2 cells. Toxicol In Vitro 21:1592–1602
34. Wilkening S, Stahl F, Bader A (2003) Comparison of primary human hepatocytes and hepatoma cell line HepG2 with regard to their biotransformation. Drug Metab Dispos 3:1035–1042
35. Winiarska-Mieczan A (2013) Protective effect of tannic acid on the brain of adults expose to cadmium and lead. Environ Toxicol Pharmacol 36:9–18
36. Yang CS, Maliakal P, Meng X (2002) Inhibition of carcinogenesis by tea. Annu Rev Pharmacol Toxicol 42:25–54
37. Yang YM, Noh K, Han CY, Kim SG (2010) Transactivation of genes encoding for phase II enzymes and phase III transporters by phytochemical antioxidants. Molecules 15:6332–6348
38. Yang Y, Sharma R, Sharma A, Awasthi S, Awasthi YC (2003) Lipid peroxidation and cell cycle signaling: 4-hydroxynonenal, a key molecule in stress mediated signaling. Acta Biochim Pol 50:319–336
39. Yeh C-T, Yen GC (2006) Induction of hepatic antioxidant enzymes by phenolic acids in rats is accompanied by increased levels of multidrug resistance-associated protein 3 mRNA expression. J Nutr 136:11–15
40. Yu X, Hensler T (2005) Nrf2 as a target for cancer chemoprevention. Mutat Res 591:93–102