title: Cancer chemopreventive activity of Xanthohumol, a natural product derived from hop.
abstract: Characterization and use of effective cancer chemopreventive agents have become important issues in public health-related research. Aiming to identify novel potential chemopreventive agents, we have established an interrelated series of bioassay systems targeting molecular mechanisms relevant for the prevention of tumor development. We report anticarcinogenic properties of Xanthohumol (XN), a prenylated chalcone from hop (Humulus Iupulus L.) with an exceptional broad spectrum of inhibitory mechanisms at the initiation, promotion, and progression stage of carcinogenesis. Consistent with anti-initiating potential, XN potently modulates the activity of enzymes involved in carcinogen metabolism and detoxification. Moreover, XN is able to scavenge reactive oxygen species, including hydroxyl- and peroxyl radicals, and to inhibit superoxide anion radical and nitric oxide production. As potential antitumor-promoting mechanisms, it demonstrates anti-inflammatory properties by inhibition of cyclooxygenase-1 and cyclooxygenase-2 activity and is antiestrogenic without possessing intrinsic estrogenic potential. Antiproliferative mechanisms of XN to prevent carcinogenesis in the progression phase include inhibition of DNA synthesis and induction of cell cycle arrest in S phase, apoptosis, and cell differentiation. Importantly, XN at nanomolar concentrations prevents carcinogen-induced preneoplastic lesions in mouse mammary gland organ culture. Because XN is easily cyclized to the flavanone isoxanthohumol, activities of both compounds were compared throughout the study. Together, our data provide evidence for the potential application of XN as a novel, readily available chemopreventive agent, and clinical investigations are warranted once efficacy and safety in animal models have been established.
authors.affiliation: Deutsches Krebstforschungszentrum, Abteilung Toxikologie und Krebsrisikofaktoren, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. c.gerhauser@dkfz.de
authors.forename: Clarissa
authors.initials: C
authors.lastname: Gerhauser
authors.forename: Axel
authors.initials: A
authors.lastname: Alt
authors.forename: Elke
authors.initials: E
authors.lastname: Heiss
authors.forename: Amira
authors.initials: A
authors.lastname: Gamal-Eldeen
authors.forename: Karin
authors.initials: K
authors.lastname: Klimo
authors.forename: Jutta
authors.initials: J
authors.lastname: Knauft
authors.forename: Isabell
authors.initials: I
authors.lastname: Neumann
authors.forename: Hans-Rudolf
authors.initials: HR
authors.lastname: Scherf
authors.forename: Norbert
authors.initials: N
authors.lastname: Frank
authors.forename: Helmut
authors.initials: H
authors.lastname: Bartsch
authors.forename: Hans
authors.initials: H
authors.lastname: Becker
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D002273:Carcinogens / Q000494:pharmacology; D002454:Cell Differentiation; D002455:Cell Division; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids; D005434:Flow Cytometry; D027582:Humulus / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007700:Kinetics; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008956:Models, Chemical; D009369:Neoplasms / Q000517:prevention & control*; D010936:Plant Extracts / Q000378:metabolism*; D011230:Precancerous Conditions; D011427:Propiophenones / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases; D016196:S Phase
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D002273:Carcinogens; D005419:Flavonoids; D007527:Isoenzymes; D008565:Membrane Proteins; D010936:Plant Extracts; D011427:Propiophenones; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; C104536:xanthohumol