Hop (Humulus lupulus L.) Extract and 6-Prenylnaringenin Induce P450 1A1 Catalyzed Estrogen 2-Hydroxylation

Chemical Research in Toxicology

Volumn 29, Issue 7, 2016, Pages 1142-1150

  Wang, Shuai ^a   Dunlap, Tareisha L ^a   Howell, Caitlin E ^a   Mbachu, Obinna C ^a   Rue, Emily A ^a   Phansalkar, Rasika ^a   Chen, Shao Nong ^a   Pauli, Guido F ^a   Dietz, Birgit M ^a   Bolton, Judy L ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 METHOXYESTRONE; 2,3,7,8 TETRACHLORODIBENZO PARA DIOXIN; 6 PRENYLNARINGENIN; 8 PRENYLNARINGENIN; AROMATIC HYDROCARBON RECEPTOR; CHALCONE DERIVATIVE; CYTOCHROME P450 1A1; CYTOCHROME P450 1B1; ESTROGEN; ETHOXYRESORUFIN DEETHYLASE; FLAVONE DERIVATIVE; HUMULUS LUPULUS EXTRACT; ISOXANTHOHUMOL; MESSENGER RNA; UNCLASSIFIED DRUG; XANTHOHUMOL; 6-PRENYLNARINGENIN; CYP1A1 PROTEIN, HUMAN; FLAVONOID; PLANT EXTRACT;

AEROBIC METABOLISM; ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER CELL LINE; CONTROLLED STUDY; DRUG HYDROXYLATION; ENZYME INHIBITION; ESTROGEN METABOLISM; HUMAN; HUMAN CELL; NONHUMAN; PROTEIN EXPRESSION; UPREGULATION; XENOBIOTIC METABOLISM; BIOSYNTHESIS; CHEMISTRY; FEMALE; GENETICS; HUMULUS; HYDROXYLATION; METABOLISM; TUMOR CELL LINE;

CELL LINE, TUMOR; CYTOCHROME P-450 CYP1A1; ESTROGENS; FEMALE; FLAVONOIDS; HUMANS; HUMULUS; HYDROXYLATION; PLANT EXTRACTS; RNA, MESSENGER;

EID: 84979009969     PISSN: 0893228X     EISSN: 15205010     Source Type: Journal    
DOI: 10.1021/acs.chemrestox.6b00112     Document Type: Article

References (73)

1. Gelety, T. J. and Judd, H. L. (1992) Menopause: new indications and management strategies Curr. Opin. Obstet. Gynecol. 4, 346-353 10.1097/00001703-199206000-00002
2. Rossouw, J. E., Anderson, G. L., Prentice, R. L., LaCroix, A. Z., Kooperberg, C., Stefanick, M. L., Jackson, R. D., Beresford, S. A. A., Howard, B. V., Johnson, K. C., Kotchen, J. M., and Ockene, J. (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women-Principal results from the Women's Health Initiative randomized controlled trial J. Am. Med. Assoc. 288, 321-333 10.1001/jama.288.3.321
3. Beral, V. (2003) Breast cancer and hormone-replacement therapy in the Million Women Study Lancet 362, 419-427 10.1016/S0140-6736(03)14065-2
4. Holmberg, L. and Anderson, H. (2004) HABITS (hormonal replacement therapy after breast cancer - is it safe?), a randomised comparison: trial stopped Lancet 363, 453-455 10.1016/S0140-6736(04)15493-7
5. Dietz, B. M., Hajirahimkhan, A., Dunlap, T. L., and Bolton, J. L. (submitted) Botanicals and their bioactive phytochemicals for women's health. Pharmacol. Rev.
6. Bailey, R. L., Gahche, J. J., Lentino, C. V., Dwyer, J. T., Engel, J. S., Thomas, P. R., Betz, J. M., Sempos, C. T., and Picciano, M. F. (2011) Dietary Supplement Use in the United States, 2003-2006 J. Nutr. 141, 261-266 10.3945/jn.110.133025
7. Cavalieri, E. and Rogan, E. (2014) The molecular etiology and prevention of estrogen-initiated cancers Mol. Aspects Med. 36, 1-55 10.1016/j.mam.2013.08.002
8. Yager, J. D. (2015) Mechanisms of estrogen carcinogenesis: The role of E2/E1-quinone metabolites suggests new approaches to preventive intervention - A review Steroids 99, 56-60 10.1016/j.steroids.2014.08.006
9. Russo, J. and Russo, I. H. (2006) The role of estrogen in the initiation of breast cancer J. Steroid Biochem. Mol. Biol. 102, 89-96 10.1016/j.jsbmb.2006.09.004
10. Dallal, C. M., Tice, J. A., Buist, D. S., Bauer, D. C., Lacey, J. V., Cauley, J. A., Hue, T. F., LaCroix, A., Falk, R. T., Pfeiffer, R. M., Fuhrman, B. J., Veenstra, T. D., Xu, X., Brinton, L. A., and Grp, B. F. R. (2014) Estrogen metabolism and breast cancer risk among postmenopausal women: a casecohort study within B similar to FIT Carcinogenesis 35, 346-355 10.1093/carcin/bgt367
11. Fuhrman, B. J., Schairer, C., Gail, M. H., Boyd-Morin, J., Xu, X., Sue, L. Y., Buys, S. S., Isaacs, C., Keefer, L. K., Veenstra, T. D., Berg, C. D., Hoover, R. N., and Ziegler, R. G. (2012) Estrogen metabolism and risk of breast cancer in postmenopausal women J. Natl. Cancer Inst. 104, 326-339 10.1093/jnci/djr531
12. Falk, R. T., Brinton, L. A., Dorgan, J. F., Fuhrman, B. J., Veenstra, T. D., Xu, X., and Gierach, G. L. (2013) Relationship of serum estrogens and estrogen metabolites to postmenopausal breast cancer risk: a nested case-control study Breast Cancer Res. 15, R34 10.1186/bcr3416
13. Lakhani, N. J., Sarkar, M. A., Venitz, J., and Figg, W. D. (2003) 2-Methoxyestradiol, a promising anticancer agent Pharmacotherapy 23, 165-172 10.1592/phco.23.2.165.32088
14. Zahid, M., Kohli, E., Saeed, M., Rogan, E., and Cavalieri, E. (2006) The greater reactivity of estradiol-3,4-quinone vs estradiol-2,3-quinone with DNA in the formation of depurinating adducts: implications for tumor-initiating activity Chem. Res. Toxicol. 19, 164-172 10.1021/tx050229y
15. Ziegler, R. G., Fuhrman, B. J., Moore, S. C., and Matthews, C. E. (2015) Epidemiologic studies of estrogen metabolism and breast cancer Steroids 99, 67-75 10.1016/j.steroids.2015.02.015
16. Lee, A. J., Cai, M. X., Thomas, P. E., Conney, A. H., and Zhu, B. T. (2003) Characterization of the oxidative metabolites of 17 beta-estradiol and estrone formed by 15 selectively expressed human cytochrome P450 isoforms Endocrinology 144, 3382-3398 10.1210/en.2003-0192
17. Nebert, D. W., Dalton, T. P., Okey, A. B., and Gonzalez, F. J. (2004) Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer J. Biol. Chem. 279, 23847-23850 10.1074/jbc.R400004200
18. Hemachandra, L. P., Madhubhani, P., Esala, R., Chandrasena, P., Chen, S. N., Main, M., Lankin, D. C., Scism, R. A., Dietz, B. M., Pauli, G. F., Thatcher, G. R. J., and Bolton, J. L. (2012) Hops (Humulus lupulus) Inhibits oxidative estrogen metabolism and estrogen-induced malignant transformation in human mammary epithelial cells (MCF-10A) Cancer Prev. Res. 5, 73-81 10.1158/1940-6207.CAPR-11-0348
19. Xu, X. and Veenstra, T. D. (2012) Concentration of endogenous estrogens and estrogen metabolites in the NCI-60 human tumor cell lines Genome Med. 4, 31 10.1186/gm330
20. Aghamiri, V., Mirghafourvand, M., Mohammad-Alizadeh-Charandabi, S., and Nazemiyeh, H. (2016) The effect of Hop (Humulus lupulus L.) on early menopausal symptoms and hot flashes: a randomized placebo-controlled trial Complement. Ther. Clin. Pract. 23, 130-135 10.1016/j.ctcp.2015.05.001
21. Keiler, A. M., Zierau, O., and Kretzschmar, G. (2013) Hop extracts and hop substances in treatment of menopausal complaints Planta Med. 79, 576-579 10.1055/s-0032-1328330
22. Chadwick, L. R., Nikolic, D., Burdette, J. E., Overk, C. R., Bolton, J. L., van Breemen, R. B., Fröhlich, R., Fong, H. H. S., Farnsworth, N. R., and Pauli, G. F. (2004) Estrogens and congeners from spent hops (Humulus lupulus) J. Nat. Prod. 67, 2024-2032 10.1021/np049783i
23. Stevens, J. F. and Page, J. E. (2004) Xanthohumol and related prenylflavonoids from hops and beer: to your good health! Phytochemistry 65, 1317-1330 10.1016/j.phytochem.2004.04.025
24. Gerhäuser, C., Alt, A., Heiss, E., Gamal-Eldeen, A., Klimo, K., Knauft, J., Neumann, I., Scherf, H. R., Frank, N., Bartsch, H., and Becker, H. (2002) Cancer chemopreventive activity of xanthohumol, a natural product derived from hop Mol. Cancer Ther. 1, 959-969
25. Dietz, B. M., Hagos, G. K., Eskra, J. N., Wijewickrama, G. T., Anderson, J. R., Nikolic, D., Guo, J., Wright, B., Chen, S. N., Pauli, G. F., van Breemen, R. B., and Bolton, J. L. (2013) Differential regulation of detoxification enzymes in hepatic and mammary tissue by hops (Humulus lupulus) in vitro and in vivo Mol. Nutr. Food Res. 57, 1055-1066 10.1002/mnfr.201200534
26. Legette, L., Karnpracha, C., Reed, R. L., Choi, J., Bobe, G., Christensen, J. M., Rodriguez-Proteau, R., Purnell, J. Q., and Stevens, J. F. (2014) Human pharmacokinetics of xanthohumol, an antihyperglycemic flavonoid from hops Mol. Nutr. Food Res. 58, 248-255 10.1002/mnfr.201300333
27. Nikolic, D., Li, Y., Chadwick, L. R., Pauli, G. F., and van Breemen, R. B. (2005) Metabolism of xanthohumol and isoxanthohumol, prenylated flavonoids from hops (Humulus lupulus L.), by human liver microsomes J. Mass Spectrom. 40, 289-299 10.1002/jms.753
28. Milligan, S. R., Kalita, J. C., Pocock, V., Van de Kauter, V., Stevens, J. F., Deinzer, M. L., Rong, H., and De Keukeleire, D. (2000) The endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus L.) flavonoids J. Clin. Endocrinol. Metab. 85, 4912-4915 10.1210/jcem.85.12.7168
29. Krause, E., Yuan, Y., Hajirahimkhan, A., Dong, H. L., Dietz, B. M., Nikolic, D., Pauli, G. F., Bolton, J. L., and van Breemen, R. B. (2014) Biological and chemical standardization of a hop (Humulus lupulus) botanical dietary supplement Biomed. Chromatogr. 28, 729-734 10.1002/bmc.3177
30. Ramos Alvarenga, R. F., Friesen, J. B., Nikolic, D., Simmler, C., Napolitano, J. G., van Breemen, R., Lankin, D. C., McAlpine, J. B., Pauli, G. F., and Chen, S. N. (2014) K-targeted metabolomic analysis extends chemical subtraction to DESIGNER extracts: selective depletion of extracts of hops (Humulus lupulus) J. Nat. Prod. 77, 2595-2604 10.1021/np500376g
31. van Breemen, R. B., Yuan, Y., Banuvar, S., Shulman, L. P., Qiu, X., Alvarenga, R. F. R., Chen, S. N., Dietz, B. M., Bolton, J. L., Pauli, G. F., Krause, E., Viana, M., and Nikolic, D. (2014) Pharmacokinetics of prenylated hop phenols in women following oral administration of a standardized extract of hops Mol. Nutr. Food Res. 58, 1962-1969 10.1002/mnfr.201400245
32. Dunlap, T. L., Wang, S., Simmler, C., Chen, S. N., Pauli, G. F., Dietz, B. M., and Bolton, J. L. (2015) Differential effects of Glycyrrhiza species on genotoxic estrogen metabolism: licochalcone A downregulates P450 1B1, whereas isoliquiritigenin stimulates it Chem. Res. Toxicol. 28, 1584-1594 10.1021/acs.chemrestox.5b00157
33. Xu, X., Roman, J. M., Issaq, H. J., Keefer, L. K., Veenstra, T. D., and Zieger, R. G. (2007) Quantitative measurement of endogenous estrogens and estrogen metabolites in human serum by liquid chromatography-tandem mass spectrometry Anal. Chem. 79, 7813-7821 10.1021/ac070494j
34. Andrieux, L., Langouet, S., Fautrel, A., Ezan, F., Krauser, J. A., Savouret, J. F., Guengerich, F. P., Baffet, G., and Guillouzo, A. (2004) Aryl hydrocarbon receptor activation and cytochrome P450 1A induction by the mitogen-activated protein kinase inhibitor U0126 in hepatocytes Mol. Pharmacol. 65, 934-943 10.1124/mol.65.4.934
35. Henderson, M. C., Miranda, C. L., Stevens, J. F., Deinzer, M. L., and Buhler, D. R. (2000) In vitro inhibition of human P450 enzymes by prenylated flavonoids from hops, Humulus lupulus Xenobiotica 30, 235-251 10.1080/004982500237631
36. Spink, D. C., Spink, B. C., Cao, J. Q., DePasquale, J. A., Pentecost, B. T., Fasco, M. J., Li, Y., and Sutter, T. R. (1998) Differential expression of CYP1A1 and CYP1B1 in human breast epithelial cells and breast tumor cells Carcinogenesis 19, 291-298 10.1093/carcin/19.2.291
37. Takemura, H., Itoh, T., Yamamoto, K., Sakakibara, H., and Shimoi, K. (2010) Selective inhibition of methoxyflavonoids on human CYP1B1 activity Bioorg. Med. Chem. 18, 6310-6315 10.1016/j.bmc.2010.07.020
38. Chaudhary, A. and Willett, K. L. (2006) Inhibition of human cytochrome CYP1 enzymes by flavonoids of St. John's wort Toxicology 217, 194-205 10.1016/j.tox.2005.09.010
39. Zhai, S., Dai, R. K., Friedman, F. K., and Vestal, R. E. (1998) Comparative inhibition of human cytochromes P450 1A1 and 1A2 by flavonoids Drug Metab. Dispos. 26, 989-992
40. Cavalieri, E., Chakravarti, D., Guttenplan, J., Hart, E., Ingle, J., Jankowiak, R., Muti, P., Rogan, E., Russo, J., Santen, R., and Sutter, T. (2006) Catechol estrogen quinones as initiators of breast and other human cancers: implications for biomarkers of susceptibility and cancer prevention Biochim. Biophys. Acta, Rev. Cancer 1766, 63-78 10.1016/j.bbcan.2006.03.001
41. Park, S. A., Na, H. K., Kim, E. H., Cha, Y. N., and Surh, Y. J. (2009) 4-Hydroxyestradiol induces anchorage-independent growth of human mammary epithelial cells via activation of I kappa B kinase: potential role of reactive oxygen species Cancer Res. 69, 2416-2424 10.1158/0008-5472.CAN-08-2177
42. Huang, Z. Q., Fasco, M. J., Figge, H. L., Keyomarsi, K., and Kaminsky, L. S. (1996) Expression of cytochromes P450 in human breast tissue and tumors Drug Metab. Dispos. 24, 899-905
43. Williams, J. A. and Phillips, D. H. (2000) Mammary expression of xenobiotic metabolizing enzymes and their potential role in breast cancer Cancer Res. 60, 4667-4677
44. Tijet, N., Boutros, P. C., Moffat, I. D., Okey, A. B., Tuomisto, J., and Pohjanvirta, R. (2006) Aryl hydrocarbon receptor regulates distinct dioxin-dependent and dioxin-independent gene batteries Mol. Pharmacol. 69, 140-153 10.1124/mol.105.018705
45. Androutsopoulos, V. P., Tsatsakis, A. M., and Spandidos, D. A. (2009) Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention BMC Cancer 9, 187 10.1186/1471-2407-9-187
46. Gajjar, K., Martin-Hirsch, P. L., and Martin, F. L. (2012) CYP1B1 and hormone-induced cancer Cancer Lett. 324, 13-30 10.1016/j.canlet.2012.04.021
47. Yang, X. H., Solomon, S., Fraser, L. R., Trombino, A. F., Liu, D. H., Sonenshein, G. E., Hestermann, E. V., and Sherr, D. H. (2008) Constitutive regulation of CYP1B1 by the aryl hydrocarbon receptor (AhR) in pre-malignant and malignant mammary tissue J. Cell. Biochem. 104, 402-417 10.1002/jcb.21630
48. Beischlag, T. V., Morales, J. L., Hollingshead, B. D., and Perdew, G. H. (2008) The aryl hydrocarbon receptor complex and the control of gene expression Crit. Rev. Eukaryotic Gene Expression 18, 207-250 10.1615/CritRevEukarGeneExpr.v18.i3.20
49. Russo, J., Lareef, A. H., Balogh, G., Guo, S., and Russo, I. H. (2003) Estrogen and its metabolites are carcinogenic agents in human breast epithelial cells J. Steroid Biochem. Mol. Biol. 87, 1-25 10.1016/S0960-0760(03)00390-X
50. Chen, Z. H., Hurh, Y. J., Na, H. K., Kim, J. H., Chun, Y. J., Kim, D. H., Kang, K. S., Cho, M. H., and Surh, Y. J. (2004) Resveratrol inhibits TCDD-induced expression of CYP1A1 and CYP1B1 and catechol estrogen-mediated oxidative DNA damage in cultured human mammary epithelial cells Carcinogenesis 25, 2005-2013 10.1093/carcin/bgh183
51. Santen, R. J., Yue, W., and Wang, J. P. (2015) Estrogen metabolites and breast cancer Steroids 99, 61-66 10.1016/j.steroids.2014.08.003
52. Fu, J. Q., Fang, H. L., Paulsen, M., Ljungman, M., Kocarek, T. A., and Runge-Morris, M. (2011) Regulation of estrogen sulfotransferase expression by confluence of MCF-10A breast epithelial cells: role of the aryl hydrocarbon receptor J. Pharmacol. Exp. Ther. 339, 597-606 10.1124/jpet.111.185173
53. Lane, M. A., Romagnoli, L., Cruise, B., and Cohn, G. M. (1999) Spontaneous conversion to estrogen receptor expression by the human breast epithelial cell line, MCF-10A Oncol. Rep. 6, 507-511 10.3892/or.6.3.507
54. van Duursen, M. B. M., Sanderson, J. T., van der Bruggen, M., van der Linden, J., and van den Burg, M. (2003) Effects of several dioxin-like compounds on estrogen metabolism in the malignant MCF-7 and nontumorigenic MCF-10A human mammary epithelial cell lines Toxicol. Appl. Pharmacol. 190, 241-250 10.1016/S0041-008X(03)00166-2
55. Huang, H. J., Chiang, P. H., and Chen, S. H. (2011) Quantitative analysis of estrogens and estrogen metabolites in endogenous MCF-7 breast cancer cells by liquid chromatography-tandem mass spectrometry J. Chromatogr. B: Anal. Technol. Biomed. Life Sci. 879, 1748-1756 10.1016/j.jchromb.2011.04.020
56. Wormke, M., Stoner, M., Saville, B., Walker, K., Abdelrahim, M., Burghardt, R., and Safe, S. (2003) The aryl hydrocarbon receptor mediates degradation of estrogen receptor alpha through activation of proteasomes Mol. Cell. Biol. 23, 1843-1855 10.1128/MCB.23.6.1843-1855.2003
57. Tiong, C. T., Chen, C., Zhang, S. J., Li, J., Soshilov, A., Denison, M. S., Lee, L. S. U., Tam, V. H., Wong, S. P., Xu, H. E., and Yong, E. L. (2012) A novel prenylflavone restricts breast cancer cell growth through AhR-mediated destabilization of ER alpha protein Carcinogenesis 33, 1089-1097 10.1093/carcin/bgs110
58. Moon, Y. J., Wang, X. D., and Morris, M. E. (2006) Dietary flavonoids: effects on xenobiotic and carcinogen metabolism Toxicol. In Vitro 20, 187-210 10.1016/j.tiv.2005.06.048
59. Zhang, S., Qin, C. H., and Safe, S. H. (2003) Flavonoids as aryl hydrocarbon receptor agonists/antagonists: effects of structure and cell context Environ. Health Perspect. 111, 1877-1882 10.1289/ehp.6322
60. Mense, S. M., Chhabra, J., and Bhat, H. K. (2008) Preferential induction of cytochrome P450 1A1 over cytochrome P4501B1 in human breast epithelial cells following exposure to quercetin J. Steroid Biochem. Mol. Biol. 110, 157-162 10.1016/j.jsbmb.2008.03.029
61. Wen, C. J., Wu, L. X., Fu, L. J., Shen, D. Y., Zhang, X., Zhang, Y. W., Yu, J., and Zhou, H. H. (2014) Preferential induction of CYP1A1 over CYP1B1 in human breast cancer MCF-7 cells after exposure to berberine Asian Pac. J. Cancer Prev. 15, 495-499 10.7314/APJCP.2014.15.1.495
62. Wen, X. and Walle, T. (2005) Preferential induction of CYP1B1 by benzo a pyrene in human oral epithelial cells: impact on DNA adduct formation and prevention by polyphenols Carcinogenesis 26, 1774-1781 10.1093/carcin/bgi127
63. Allen, S. W., Mueller, L., Williams, S. N., Quattrochi, L. C., and Raucy, J. (2001) The use of a high-volume screening procedure to assess the effects of dietary flavonoids on human CYP1A1 expression Drug Metab. Dispos. 29, 1074-1079
64. Gross-Steinmeyer, K., Stapleton, P. L., Liu, F., Tracy, J. H., Bammler, T. K., Quigley, S. D., Farin, F. M., Buhler, D. R., Safe, S. H., Strom, S. C., and Eaton, D. L. (2004) Phytochemical-induced changes in gene expression of carcinogen-metabolizing enzymes in cultured human primary hepatocytes Xenobiotica 34, 619-632 10.1080/00498250412331285481
65. Smerdova, L., Smerdova, J., Kabatkova, M., Kohoutek, J., Blazek, D., Machala, M., and Vondracek, J. (2014) Upregulation of CYP1B1 expression by inflammatory cytokines is mediated by the p38 MAP kinase signal transduction pathway Carcinogenesis 35, 2534-2543 10.1093/carcin/bgu190
66. Hu, W. Y., Sorrentino, C., Denison, M. S., Kolaja, K., and Fielden, M. R. (2007) Induction of CYP1A1 is a nonspecific biomarker of aryl hydrocarbon receptor activation: Results of large scale screening of pharmaceuticals and toxicants in vivo and in vitro Mol. Pharmacol. 71, 1475-1486 10.1124/mol.106.032748
67. Lu, F., Zahid, M., Wang, C., Saeed, M., Cavalieri, E. L., and Rogan, E. G. (2008) Resveratrol prevents estrogen-DNA adduct formation and neoplastic transformation in MCF-10F cells Cancer Prev. Res. 1, 135-145 10.1158/1940-6207.CAPR-08-0037
68. Shimada, T., Tanaka, K., Takenaka, S., Murayama, N., Martin, M. V., Foroozesh, M. K., Yamazaki, H., Guengerich, F. P., and Komori, M. (2010) Structure-function relationships of inhibition of human cytochromes P450 1A1, 1A2, 1B1, 2C9, and 3A4 by 33 flavonoid derivatives Chem. Res. Toxicol. 23, 1921-1935 10.1021/tx100286d
69. Leung, H. Y., Wang, Y., Chan, H. Y., and Leung, L. K. (2007) Developing a high-throughput system for the screening of cytochrome P450 1A1-Inhibitory polyphenols Toxicol. In Vitro 21, 996-1002 10.1016/j.tiv.2007.04.005
70. Wang, H., Wang, Y., Chen, Z. Y., Chan, F. L., and Leung, L. K. (2005) Hydroxychalcones exhibit differential effects on XRE transactivation Toxicology 207, 303-313 10.1016/j.tox.2004.10.005
71. Yuan, Y., Qiu, X., Nikolic, D., Chen, S. N., Huang, K., Li, G. N., Pauli, G. F., and van Breemen, R. B. (2014) Inhibition of human cytochrome P450 enzymes by hops (Humulus lupulus) and hop prenylphenols Eur. J. Pharm. Sci. 53, 55-61 10.1016/j.ejps.2013.12.003
72. Monteiro, R., Becker, H., Azevedo, I., and Calhau, C. (2006) Effect of hop (Humulus lupulus L.) flavonoids on aromatase (estrogen synthase) activity J. Agric. Food Chem. 54, 2938-2943 10.1021/jf053162t
73. Possemiers, S., Bolca, S., Grootaert, C., Heyerick, A., Decroos, K., Dhooge, W., De Keukeleire, D., Rabot, S., Verstraete, W., and Van de Wiele, T. (2006) The prenylflavonoid isoxanthohumol from hops (Humulus lupulus L.) is activated into the potent phytoestrogen 8-prenylnaringenin in vitro and in the human intestine J. Nutr. 136, 1862-1867