Cancer chemopreventive potential of humulones and isohumulones (hops α- and iso-α-acids): Induction of NAD(P)H:quinone reductase as a novel mechanism

Natural Product Communications

Volumn 3, Issue 12, 2008, Pages 1971-1976

  Bohr, Gregor ^a   Klimo, Karin ^b   Zapp, Josef ^a   Becker, Hans ^a   Gerhäuser, Clarissa ^b  

^a SAARLAND UNIVERSITY   (Germany)

^b GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

Author keywords

Cancer chemoprevention; Hops; Hops iso acids; Hops acids; Humulinone; Humulone; Humulus lupulus L.; Isohumulone; NAD(P)H:quinone reductase

Indexed keywords

HUMULINONE; HUMULON; HUMULUS LUPULUS EXTRACT; I KAPPA B; INDUCIBLE NITRIC OXIDE SYNTHASE; ISOHUMULONE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE); UNCLASSIFIED DRUG;

ANIMAL CELL; ANTIOXIDANT ACTIVITY; ARTICLE; CELL CULTURE; CHEMOPROPHYLAXIS; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOTOXICITY; DRUG ISOLATION; DRUG SYNTHESIS; ENZYME ACTIVITY; FRACTIONATION; HEPATOMA CELL; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HOPS; HUMULUS LUPULUS; IC 50; MASS SPECTROMETRY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PHYTOCHEMISTRY;

ANIMALIA; HUMULUS; HUMULUS LUPULUS;

EID: 77950672898     PISSN: 1934578X     EISSN: 15559475     Source Type: Journal    
DOI: 10.1177/1934578x0800301206     Document Type: Article

References (43)

1. Verzele M. (1986) 100-Years of hop chemistry and its relevance to brewing. Journal of the Institute of Brewing, 92, 32-48.
2. Teuber M, Schmalreck AF. (1973) Membrane leakage in Bacillus subtilis 168 induced by the hop constituents lupulone, humulone, isohumulone and humulinic acid. Archives of Microbiology, 94, 159-171.
3. (a) De Keukeleire D, De Cooman L, Rong H, Heyerick A, Kalita J, Milligan SR. (1999) Functional properties of hop polyphenols. Basic Life Sciences, 66, 739-760;
4. (b) Hughes P. (2000) The significance of iso-α-acids for beer quality - Cambridge prize paper. Journal of the Institute of Brewing, 106, 271-276;
5. (c) De Keukeleire D. (2000) Fundamentals of beer and hop chemistry. Quimica Nova, 23, 108-112.
6. (a) Stevens JF, Page JE. (2004) Xanthohumol and related prenylflavonoids from hops and beer: to your good health! Phytochemistry, 65, 1317-1330;
7. (b) Kondo K. (2004) Beer and health: preventive effects of beer components on lifestyle-related diseases. Biofactors, 22, 303-310;
8. (c) Gerhauser C. (2005) Beer constituents as potential cancer chemopreventive agents. European Journal of Cancer, 41, 1941-1954.
9. Lee JC, Kundu JK, Hwang DM, Na HK, Surh YJ. (2007) Humulone inhibits phorbol ester-induced COX-2 expression in mouse skin by blocking activation of NF-κB and AP-1: I-κB kinase and c-Jun-N-terminal kinase as respective potential upstream targets. Carcinogenesis, 28, 1491-1498.
10. (a) Nozawa H, Nakao W, Zhao F, Kondo K. (2005) Dietary supplement of isohumulones inhibits the formation of aberrant crypt foci with a concomitant decrease in prostaglandin E2 level in rat colon. Molecular Nutrition and Food Research, 49, 772-778;
11. (b) Shindo S, Tomatsu M, Nakda T, Shibamoto N, Tachibana T, Mori K. (2002) Inhibition of aldose reductase activity by extracts from hops. Journal of the Institute of Brewing, 108, 344-347;
12. (c) Yajima H, Ikeshima E, Shiraki M, Kanaya T, Fujiwara D, Odai H, Tsuboyama-Kasaoka N, Ezaki O, Oikawa S, Kondo K. (2004) Isohumulones, bitter acids derived from hops, activate both peroxisome proliferator-activated receptor α and γ and reduce insulin resistance. Journal of Biological Chemistry, 279, 33456-33462;
13. (d) Yajima H, Noguchi T, Ikeshima E, Shiraki M, Kanaya T, Tsuboyama-Kasaoka N, Ezaki O, Oikawa S, Kondo K. (2005) Prevention of diet-induced obesity by dietary isomerized hop extract containing isohumulones, in rodents. International Journal of Obesity (London), 29, 991-997;
14. (e) Miura Y, Hosono M, Oyamada C, Odai H, Oikawa S, Kondo K. (2005) Dietary isohumulones, the bitter components of beer, raise plasma HDL-cholesterol levels and reduce liver cholesterol and triacylglycerol contents similar to PPARalpha activations in C57BL/6 mice. British Journal of Nutrition, 93, 559-567;
15. (f) Shimura M, Hasumi A, Minato T, Hosono M, Miura Y, Mizutani S, Kondo K, Oikawa S, Yoshida A. (2005) Isohumulones modulate blood lipid status through the activation of PPAR alpha. Biochimica et Biophysica Acta, 1736, 51-60;
16. (g) Namikoshi T, Tomita N, Fujimoto S, Haruna Y, Ohzeki M, Komai N, Sasaki T, Yoshida A, Kashihara N. (2007) Isohumulones derived from hops ameliorate renal injury via an anti-oxidative effect in Dahl salt-sensitive rats. Hypertension Research, 30, 175-184.
17. 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. Molecular Cancer Therapeutics, 1, 959-969.
18. Bohr G, Gerhauser C, Knauft J, Zapp J, Becker H. (2005) Anti-inflammatory acylphloroglucinol derivatives from hops (Humulus lupulus). Journal of Natural Products, 68, 1545-1548.
19. Biendl M, Methner F-J, Stettner G, Walker CJ. (2004) Brauversuche mit einem xanthohumolreichen Hopfenprodukt. Brauwelt, 144, 236-244.
20. (a) Meheus J, Verzele M, Alderweireldt F. (1964) Humulinone. Bulletin Des Societes Chimiques Belges, 73, 268-273;
21. (b) Verzele M, De Keukeleire D. (1991) Chemistry and analysis of hop and beer bitter acids. Elsevier Science Publishers B.V., Amsterdem, New York, 1-417;
22. (c) Nord LI, Sorensen SB, Duus JO. (2003) Characterization of reduced iso-α-acids derived from hops (Humulus lupulus) by NMR. Magnetic Resonance in Chemistry, 41, 660-670;
23. (d) Vanhoenacker G, De Keukeleire D, Sandra P. (2004) Analysis of iso-α-acids and reduced iso-α-acids in beer by direct injection and liquid chromatography with ultraviolet absorbance detection or with mass spectrometry. Journal of Chromatography A, 1035, 53-61;
24. (e) Chadwick LR, Nikolic D, Burdette JE, Overk CR, Bolton JL, van Breemen RB, Frohlich R, Fong HH, Farnsworth NR, Pauli GF. (2004) Estrogens and congeners from spent hops (Humulus lupulus). Journal of Natural Products, 67, 2024-2032;
25. (f) Khatib A, Wilson EG, Kim HK, Supardi M, Choi YH, Verpoorte R. (2007) NMR assignment of iso-α-acids from isomerised extracts of Humulus lupulus L. cones. Phytochemical Analysis, 18, 371-377.
26. Hermans-Lokkerbol ACJ, Verpoorte R. (1994) Preparative separation and isolation of three α-bitter acids from hop, Humulus lupulus L, by centrifugal partition chromatography. Journal of Chromatography A, 664, 45-53.
27. Sporn MB, Newton DL. (1979) Chemoprevention of cancer with retinoids. Federation Proceedings, 38, 2528-2534.
28. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. (2007) Free radicals and antioxidants in normal physiological functions and human disease. International Journal of Biochemistry and Cell Biology, 39, 44-84. (Pubitemid 44566469)
29. Tagashira M, Watanabe M, Uemitsu N. (1995) Antioxidative activity of hop bitter acids and their analogues. Bioscience Biotechnology and Biochemistry, 59, 740-742.
30. Gerhauser C, Klimo K, Heiss E, Neumann I, Gamal-Eldeen A, Knauft J, Liu GY, Sitthimonchai S, Frank N. (2003) Mechanismbased in vitro screening of potential cancer chemopreventive agents. Mutation Research, 523-524, 163-172.
31. Jaiswal AK. (2000) Regulation of genes encoding NAD(P)H:quinone oxidoreductases. Free Radical Biology and Medicine, 29, 254-262.
32. Eggler AL, Gay KA, Mesecar AD. (2008) Molecular mechanisms of natural products in chemoprevention: induction of cytoprotective enzymes by Nrf2. Molecular Nutrition and Food Research, 52 (Suppl 1): S84-94.
33. Ohshima H, Bartsch H. (1994) Chronic infections and inflammatory processes as cancer risk-factors - Possible role of nitric-oxide in carcinogenesis. Mutation Research, 305, 253-264.
34. (a) Gerhauser C, Heiss E, Herhaus C, Klimo K. (2001) Potential chemopreventive mechanisms of chalcones. In: Dietary anticarcinogens and antimutagens: chemical and biological aspects Vol. 4.4, Johnson IT, Fenwick GR (Eds.), Royal Society of Chemistry, Cambridge, 189-192;
35. (b) Heiss E, Herhaus C, Klimo K, Bartsch H, Gerhauser C. (2001) Nuclear factor kappa B is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms. Journal of Biological Chemistry, 276, 32008-32015;
36. (c) Dinkova-Kostova AT, Liby KT, Stephenson KK, Holtzclaw WD, Gao X, Suh N, Williams C, Risingsong R, Honda T, Gribble GW, Sporn MB, Talalay P. (2005) Extremely potent triterpenoid inducers of the phase 2 response: correlations of protection against oxidant and inflammatory stress. Proceedings of the National Academy of Sciences of the United States of America, 102, 4584-4589.
37. Yamamoto K, Wang J, Yamamoto S, Tobe H. (2000) Suppression of cyclooxygenase-2 gene transcription by humulone of beer hop extract studied with reference to glucocorticoid. FEBS Letters, 465, 103-106.
38. Zhao F, Nozawa H, Daikonnya A, Kondo K, Kitanaka S. (2003) Inhibitors of nitric oxide production from hops (Humulus lupulus L.). Biological & Pharmaceutical Bulletin, 26, 61-65. (Pubitemid 39663644)
39. Nozawa H, Nakao W, Takata J, Arimoto-Kobayashi S, Kondo K. (2006) Inhibition of PhIP-induced mammary carcinogenesis in female rats by ingestion of freeze-dried beer. Cancer Letters, 235, 121-129.
40. Carl H. (1997) Hops and Hop Products (Manual of good practice). EBC Technology and Engineering Forum, Nürnberg, pp. 67-68.
41. (a) Pusecker K, Albert K, Bayer E. (1999) Investigation of hop and beer bitter acids by coupling of high-performance liquid chromatography to nuclear magnetic resonance spectroscopy. Journal of Chromatography A, 836, 245-252;
42. (b) Hoek AC, Hermans-Lokkerbol ACJ, Verpoorte R. (2001) An improved NMR method for the quantification of alpha-acids in hops and hop products. Phytochemical Analysis, 12, 53-57.
43. Prochaska HJ, Santamaria AB. (1988) Direct measurement of NAD(P)H:quinone reductase from cells cultured in microtiter wells: a screening assay for anticarcinogenic enzyme inducers. Analytical Biochemistry, 169, 328-336.