Deutsches Krebstforschungszentrum, Abteilung
Toxikologie und Krebsrisikofaktoren, Im Neuenheimer Feld 280, 69120
Heidelberg, Germany. c.gerhauser@dkfz.de
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.PMID: 12481418 [PubMed - indexed for MEDLINE
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