Hostname: page-component-586b7cd67f-gb8f7 Total loading time: 0 Render date: 2024-11-22T20:11:50.120Z Has data issue: false hasContentIssue false
  • English
  • Français

The red clover (Trifolium pratense) isoflavone biochanin A modulates the biotransformation pathways of 7, 12-dimethylbenz[a]anthracene

Published online by Cambridge University Press:  07 June 2007

Ho Yee Chan ,
Huan Wang  and
Lai K. Leung
Ho Yee Chan
Affiliation:
Department of Biochemistry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong
Huan Wang
Affiliation:
Department of Biochemistry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong
Lai K. Leung*
Affiliation:
Food and Nutritional Sciences Programme, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong Department of Biochemistry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong
*
*Corresponding author: Dr Lai K. Leung, fax +852 2603 7732, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Several flavonoids have shown their anti-carcinogenic effects in various models. The soyabean isoflavone genistein was demonstrated earlier in our laboratory to be an effective inhibitor of dimethylbenz[a]anthracene (DMBA)-induced DNA damage in MCF-7 cells by curbing cytochrome P450 (CYP) 1 enzymes. The red clover (Trifolium pratense) isoflavone biochanin A is a methylated derivative of genistein, and its anti-mutagenic effect in bacterial cells has been shown previously. Because of its protection against chemical carcinogenesis in an animal model, biochanin A was selected for testing in our established MCF-7 cell system. From the results obtained in the semi-quantitative reverse transcription–polymerase chain reaction and xenobiotic response element (XRE)–luciferase reporter assays, biochanin A could reduce xenobiotic-induced CYP1A1 and -1B1 mRNA abundances through the interference of XRE-dependent transactivation. Enzyme kinetic studies also indicated that biochanin A inhibited both CYP1A1 and -1B1 enzymes with inhibition constant (Ki) values 4·00 and 0·59μM respectively. Since the biotransformation of DMBA was dependent on CYP1 enzyme activities, biochanin A was able to decrease the DMBA–DNA lesions. The present study illustrated that the red clover isoflavone could protect against polycylic aromatic hydrocarbon-induced DNA damage.

Keywords

Biochanin ACytochrome P450 1A1Cytochrome P450 1B17,12-Dimethylbenz[a]anthracene–DNA lesion
Type
Research Article
Information
British Journal of Nutrition , Volume 90 , Issue 1 , July 2003 , pp. 87 - 92
Copyright
Copyright © The Nutrition Society 2003

References

Backlund, M, Johansson, I, Mkrtchian, S & Ingelman-Sundberg, M (1997) Signal transduction-mediated activation of the aryl hydrocarbon receptor in rat hepatoma H4IIE cells. J Biol Chem 272, 31755–31763.CrossRefGoogle ScholarPubMed
Buters, JT, Sakai, S & Richter, T (1999) Cytochrome P450 CYP1B1 determines susceptibility to 7,12-dimethylbenz[a]anthracene-induced lymphomas. Proc Natl Acad Sci USA 96, 1977–1982.CrossRefGoogle ScholarPubMed
Chae, YH, Coffing, SL, Cook, VM, Ho, DK, Cassady, JM & Baird, WM (1991) Effects of biochanin A on metabolism, DNA binding and mutagenicity of benzo[a]pyrene in memmalian cell cultures. Carcinogenesis 12, 2001–2006.CrossRefGoogle Scholar
Chae, YH, Ho, DK, Cassady, JM, Cook, VM, Marcus, CB & Baird, WM (1992) Effects of synthetic and naturally occurring flavonoids on metabolic activation of benzo[a]pyrene in hamster embryo cell cultures. Chem Biol Interact 82, 181–193.CrossRefGoogle Scholar
Chan, HY, Chen, ZY, Tsang, DSC & Leung, LK (2002) Baicalein reduces DMBA-DNA adduct formation by modulating CYP1A1 and CYP1B1. Biomed Pharmacother 56, 269–275.CrossRefGoogle ScholarPubMed
Ciolino, HP, Daschner, PJ, Wang, TT & Yeh, GC (1998) Effect of curcumin on the aryl hydrocarbon receptor and cytochrome P450 1A1 in MCF-7 human breast carcinoma cells. Biochem Pharmacol 56, 197–206.CrossRefGoogle ScholarPubMed
Ciolino, HP, Daschner, PJ & Yeh, GC (1999) The flavonoid galangin is an inhibitor of CYP1A1 activity and an agonist/antagonist of the aryl hydrocarbon receptor. Br J Cancer 79, 1340–1346.CrossRefGoogle Scholar
Ciolino, HP, Daschner, PJ & Yeh, GC (1999) Dietary flavonols quercetin and kaempferol are ligands of the aryl hydrocarbon receptor that affect CYP1A1 transcription differentially. Biochem J 340, 715–722.CrossRefGoogle ScholarPubMed
Ciolino, HP & Yeh, GC (1999) Inhibition of aryl hydrocarbon-induced cytochrome P-450 1A1 enzyme activity and CYP1A1 expression by resveratrol. Mol Pharmacol 56, 760–767.Google ScholarPubMed
Dertinger, SD, Lantum, HB, Silverstone, AE & Gasiewicz, TA (2000) Effect of 3′-methoxy-4′-nitroflavone on benzo[a]pyrene toxicity. Aryl hydrocarbon receptor-dependent and -independent mechanisms. Biochem Pharmacol 60, 189–196.CrossRefGoogle Scholar
Dohr, O, Vogel, C & Abel, J (1995) Different response of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-sensitive genes in human breast cancer MCF-7 and MDA-MB 231 cells. Arch Biochem Biophys 321, 405–412.CrossRefGoogle ScholarPubMed
Environmental Protection Agency (1990) Aerometric Information Retrieval System (AIRS), Data for 1985–1990, DC, USA: Environmental Protection Agency, US Government Printing Office.Google Scholar
Francis, AR, Shetty, TK & Bhattacharya, RK (1989 a) Modifying role of dietary factors on the mutagenicity of aflatoxin B1: in vitro effect of plant flavonids. Mutat Res 222, 393–401.CrossRefGoogle Scholar
Francis, AR, Shetty, TK & Bhattacharya, RK (1989) Modulating effect of plant flavonoids on the mutagenicity of N-methyl-N′-nitro-N-nitrosoguanidine. Carcinogenesis 10, 1953–1955.CrossRefGoogle ScholarPubMed
Gonzalez, FJ & Gelboin, HV (1994) Role of human cytochromes P450 in the metabolic activation of chemical carcinogens and toxins. Drug Metab Rev 26, 165–183.CrossRefGoogle ScholarPubMed
Gotoh, T, Yamada, K, Yin, H, Ito, A, Kataoka, T & Dohi, K (1998) Chemoprevention of N-nitroso-N-methylurea-induced rat mammary carcinogenesis by soy foods or biochanin A. Jpn J Cancer Res 89, 137–142.CrossRefGoogle ScholarPubMed
Higginson, J, Muir, CS & Munoz, N (1992) In Cambridge Monographs on Cancer Research, Human Cancer: Epidemiology and Environmental Causes. pp 377–387. Cambridge: Cambridge University Press.CrossRefGoogle Scholar
International Agency for Research on Cancer (1983) Polynuclear aromatic compounds. Part I: Chemical, environmental and experimental data. In IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. vol. 32, pp 1–453. Lyon: IARC.Google Scholar
Kleiner, HE, Vulimiri, SV, Reed, MJ, Uberecken, A & DiGiovanni, J (2002) Role of cytochrome P450 1a1 and 1b1 in the metabolic activation of 7,12-dimethylbenz-[a]anthracene and the effects of naturally occurring furanocoumarins on skin tumor initiation. Chem Res Toxicol 15, 226–235.CrossRefGoogle Scholar
Kronenberg, S, Esser, C & Carlberg, C (2000) An aryl hydrocarbon receptor conformation acts as the functional core of nuclear dioxin signaling. Nucleic Acids Res 28, 2286–2291.CrossRefGoogle ScholarPubMed
Li, D, Wang, M, Dhingra, K & Hittelman, WN (1996) Aromatic DNA adducts in adjacent tissues of breast cancer patients: clues to breast cancer etiology. Cancer Res 56, 287–293.Google ScholarPubMed
MacDonald, CJ, Ciolino, HP & Yeh, GC (2001) Dibenzoylmethane modulates aryl hydrocarbon receptor function and expression of cytochromes P50 1A1, 1A2, and 1B1. Cancer Res 61, 3919–3924.Google ScholarPubMed
Mosmann, T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65, 55–63.CrossRefGoogle ScholarPubMed
Mizunuma, H, Kanazawa, K, Ogura, S, Otsuka, S & Nagai, H (2002) Anticarcinogenic effects of isoflavones may be mediated by genistein in mouse mammary tumor virus-induced breast cancer. Oncology 62, 78–84.CrossRefGoogle ScholarPubMed
Peterson, TG, Coward, L, Kirk, M, Falany, CN & Barnes, S (1996) The role of metabolism in mammary epithelial cell growth inhibition by the isoflavones genistein and biochanin A. Carcinogenesis 17, 1861–1869.CrossRefGoogle ScholarPubMed
Peterson, TG, Ji, GP, Kirk, M, Coward, L, Falany, CN & Barnes, S (1998) Metabolism of the isoflavones genistein and biochanin A in human breast cancer cell lines. Am J Clin Nutr 68(Suppl.), 1505S–1511S.CrossRefGoogle ScholarPubMed
Safe, S (2001) Molecular biology of the Ah receptor and its role in carcinogenesis. Toxicol Lett 120, 1–7.CrossRefGoogle Scholar
Shimizu, Y, Nakatsuru, Y & Ichinose, M (2000) Benzo[a]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor. Proc Natl Acad Sci USA 97, 779–782.CrossRefGoogle Scholar
Taioli, E (1999) International collaborative study on genetic susceptibility to environmental carcinogens. Cancer Epidemiol Biomarkers Prev 8, 727–728.Google Scholar
Wang, TT & Phang, JM (1995) Effects of estrogen on apoptotic pathways in human breast cancer cell line MCF-7. Cancer Res 55, 2487–2489.Google ScholarPubMed
Zheng, W, Xie, DW & Jin, F (2000) Genetic polymorphism of P450 1B1 and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 9, 147–150.Google ScholarPubMed
Ziegler, RG, Hoover, RN & Pike, MC (1993) Migration patterns and breast cancer risk in Asian-American women. J Natl Cancer Inst 85, 1819–1827.CrossRefGoogle ScholarPubMed