Cancer Letters
Volume 246, Issue 1 , Pages 201-209 , 8 February 2007

Xanthohumol, a prenylflavonoid derived from hops induces apoptosis and inhibits NF-kappaB activation in prostate epithelial cells

  • Emily C. Colgate

      Affiliations

    • Department of Nutrition and Exercise Sciences, Oregon State University, Corvallis, OR, USA
  • ,
  • Cristobal L. Miranda

      Affiliations

    • Environmental Molecular Toxicology, Oregon State University, Corvallis, OR, USA
    • Pharmaceutical Sciences, Oregon State University, Corvallis, OR, USA
  • ,
  • Jan F. Stevens

      Affiliations

    • Pharmaceutical Sciences, Oregon State University, Corvallis, OR, USA
    • Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
  • ,
  • Tammy M. Bray

      Affiliations

    • Department of Nutrition and Exercise Sciences, Oregon State University, Corvallis, OR, USA
    • Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
  • ,
  • Emily Ho

      Affiliations

    • Department of Nutrition and Exercise Sciences, Oregon State University, Corvallis, OR, USA
    • Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
    • Corresponding Author InformationCorresponding author. Address: Department of Nutrition and Exercise Sciences, Oregon State University, 108 Milam, Corvallis, OR 97331, USA. Tel.: +1 541 737 9559; fax: +1 541 737 6914.

Received 29 October 2005 ,Revised 30 January 2006 ,Accepted 20 February 2006.

References 

  1. Stevens JF, Page JE. Xanthohumol and related prenylflavonoids from hops and beer: to your good health. Phytochemistry. 2004;65:1317–1330
  2. Dietz BM, Kang YH, Liu G, Eggler AL, Yao P, Chadwick LR, et al. Xanthohumol isolated from humulus lupulus inhibits menadione-induced DNA damage through induction of quinone reductase. Chem. Res. Toxicol. 2005;18:1296–1305
  3. Gerhauser C, Alt A, Heiss E, Gamal-Eldeen A, Klimo K, Knauft J, et al. Cancer chemopreventive activity of Xanthohumol, a natural product derived from hop. Mol. Cancer Ther. 2002;1:959–969
  4. Goto K, Asai T, Hara S, Namatame I, Tomoda H, Ikemoto M, et al. Enhanced antitumor activity of xanthohumol, a diacylglycerol acyltransferase inhibitor, under hypoxia. Cancer Lett. 2005;219:215–222
  5. Miranda CL, Yang YH, Henderson MC, Stevens JF, Santana-Rios G, Deinzer ML, et al. Prenylflavonoids from hops inhibit the metabolic activation of the carcinogenic heterocyclic amine 2-amino-3-methylimidazo[4, 5-f]quinoline, mediated by cDNA-expressed human CYP1A2. Drug Metab. Dispos. 2000;28:1297–1302
  6. Stevens JF, Miranda CL, Frei B, Buhler DR. Inhibition of peroxynitrite-mediated LDL oxidation by prenylated flavonoids: the alpha,beta-unsaturated keto functionality of 2′-hydroxychalcones as a novel antioxidant pharmacophore. Chem. Res. Toxicol. 2003;16:1277–1286
  7. Vanhoecke B, Derycke L, Van Marck V, Depypere H, De Keukeleire D, Bracke M. Antiinvasive effect of xanthohumol, a prenylated chalcone present in hops (Humulus lupulus L.) and beer. Int. J. Cancer. 2005;
  8. Zhao F, Nozawa H, Daikonnya A, Kondo K, Kitanaka S. Inhibitors of nitric oxide production from hops (Humulus Lupulus L.). Biol. Pharm. Bull. 2003;26:61–65
  9. Gerhauser C. Beer constituents as potential cancer chemopreventive agents. Eur. J. Cancer. 2005;
  10. Steele VE, Boone CW, Lubet RA, Crowell JA, Holmes CA, Sigman CC, et al. Preclinical drug development paradigms for chemopreventives. Hematol. Oncol. Clin. North Am. 1998;12:943–961(see also pages v–vi)
  11. Tsuda H, Ohshima Y, Nomoto H, Fujita K, Matsuda E, Iigo M, et al. Cancer prevention by natural compounds. Drug Metab. Pharmacokinet. 2004;19:245–263
  12. Baldwin AS. Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB. J. Clin. Invest. 2001;107:241–246
  13. Rayet B, Gelinas C. Aberrant rel/nfkb genes and activity in human cancer. Oncogene. 1999;18:6938–6947
  14. Stevens JF, Taylor AW, Deinzer ML. Quantitative analysis of xanthohumol and related prenylflavonoids in hops and beer by liquid chromatography–tandem mass spectrometry. J. Chromatogr. A. 1999;832:97–107
  15. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods. 1983;65:55–63
  16. Martin SJ, Reutelingsperger CP, McGahon AJ, Rader JA, van Schie RC, LaFace DM, et al. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J. Exp. Med. 1995;182:1545–1556
  17. Diaz GD, Li Q, Dashwood RH. Caspase-8 and apoptosis-inducing factor mediate a cytochrome c-independent pathway of apoptosis in human colon cancer cells induced by the dietary phytochemical chlorophyllin. Cancer Res. 2003;63:1254–1261
  18. Pan L, Becker H, Gerhauser C. Xanthohumol induces apoptosis in cultured 40-16 human colon cancer cells by activation of the death receptor- and mitochondrial pathway. Mol. Nutr. Food Res. 2005;
  19. Lust S, Vanhoecke B, Janssens A, Philippe J, Bracke M, Offner F. Xanthohumol kills B-chronic lymphocytic leukemia cells by an apoptotic mechanism. Mol. Nutr. Food Res. 2005;49:844–850
  20. Nikolic D, Li Y, Chadwick LR, Pauli GF, van Breemen RB. Metabolism of xanthohumol and isoxanthohumol, prenylated flavonoids from hops (Humulus lupulus L.), by human liver microsomes. J. Mass. Spectrom. 2005;40:289–299
  21. Baeuerle PA, Henkel T. Function and activation of NF-kappa B in the immune system. Annu. Rev. Immunol. 1994;12:141–179
  22. Yeh KY, Yeh M, Glass J, Granger DN. Rapid activation of NF-kappaB and AP-1 and target gene expression in postischemic rat intestine. Gastroenterology. 2000;118:525–534
  23. De Plaen IG, Tan XD, Chang H, Qu XW, Liu QP, Hsueh W. Intestinal NF-kappaB is activated, mainly as p50 homodimers, by platelet-activating factor. Biochim. Biophys. Acta. 1998;1392:185–192
  24. Thompson JE, Phillips RJ, Erdjument-Bromage H, Tempst P, Ghosh S. I kappa B-beta regulates the persistent response in a biphasic activation of NF-kappa B. Cell. 1995;80:573–582
  25. Malek S, Huxford T, Ghosh G. Ikappa Balpha functions through direct contacts with the nuclear localization signals and the DNA binding sequences of NF-kappaB. J. Biol. Chem. 1998;273:25427–25435
  26. Gasparian AV, Yao YJ, Kowalczyk D, Lyakh LA, Karseladze A, Slaga TJ, et al. The role of IKK in constitutive activation of NF-kappaB transcription factor in prostate carcinoma cells. J. Cell Sci. 2002;115:141–151
  27. Lessard L, Mes-Masson AM, Lamarre L, Wall L, Lattouf JB, Saad F. NF-kappa B nuclear localization and its prognostic significance in prostate cancer. BJU Int. 2003;91:417–420
  28. Levine L, Lucci JA, Pazdrak B, Cheng JZ, Guo YS, Townsend CM, et al. Bombesin stimulates nuclear factor kappa B activation and expression of proangiogenic factors in prostate cancer cells. Cancer Res. 2003;63:3495–3502
  29. Suh J, Payvandi F, Edelstein LC, Amenta PS, Zong WX, Gelinas C, et al. Mechanisms of constitutive NF-kappaB activation in human prostate cancer cells. Prostate. 2002;52:183–200
  30. Gunawardena K, Murray DK, Swope RE, Meikle AW. Inhibition of nuclear factor kappaB induces apoptosis following treatment with tumor necrosis factor alpha and an antioxidant in human prostate cancer cells. Cancer Detect. Prev. 2002;26:229–237
  31. Miranda CL, Stevens JF, Helmrich A, Henderson MC, Rodriguez RJ, Yang YH, et al. Antiproliferative and cytotoxic effects of prenylated flavonoids from hops (Humulus lupulus) in human cancer cell lines. Food Chem. Toxicol. 1999;37:271–285
  32. Miranda CL, Aponso GL, Stevens JF, Deinzer ML, Buhler DR. Prenylated chalcones and flavanones as inducers of quinone reductase in mouse Hepa 1c1c7 cells. Cancer Lett. 2000;149:21–29
  33. Liu G, Eggler AL, Dietz BM, Mesecar AD, Bolton JL, Pezzuto JM, et al. Screening method for the discovery of potential cancer chemoprevention agents based on mass spectrometric detection of alkylated Keap1. Anal. Chem. 2005;77:6407–6414
  34. Hussong R, Frank N, Knauft J, Ittrich C, Owen R, Becker H, et al. A safety study of oral xanthohumol administration and its influence on fertility in sprague dawley rats. Mol. Nutr. Food Res. 2005;49:861–867

PII: S0304-3835(06)00123-6

doi: 10.1016/j.canlet.2006.02.015

Cancer Letters
Volume 246, Issue 1 , Pages 201-209 , 8 February 2007