Identification and use of effective
cancer chemopreventive agents have become an important issue in public health-related research. For identification of potential
cancer chemopreventive constituents we have set up a battery of cell- and
enzyme-based in vitro marker systems relevant for prevention of
carcinogenesis in vivo. These systems include modulation of drug metabolism (inhibition of Cyp1A activity, induction of
NAD(P)H:
quinone reductase (QR) activity in Hepa1c1c7 murine
hepatoma cell culture), determination of radical scavenging (DPPH scavenging) and
antioxidant effects (scavenging of
superoxide anion-,
hydroxyl- and peroxyl-radicals), anti-inflammatory mechanisms (inhibition of
lipopolysaccharide (LPS)-mediated
nitric oxide (NO) generation by inducible
NO synthase (iNOS) in Raw 264.7 murine macrophages,
cyclooxygenase-1 (Cox-1) inhibition), and anti-
tumor promoting activities (inhibition of
phorbol ester-induced
ornithine decarboxylase (ODC) activity in 308 murine keratinocytes). We have tested a series of known chemopreventive substances belonging to several structural classes as reference compounds for the identification of novel chemopreventive agents or mechanisms. These include organosulfur compounds (
phenethylisothiocyanate (
PEITC),
diallylsulfide, diallyldisulfide),
terpenes (
limonene,
perillyl alcohol,
oleanolic acid, 18-beta-
glycyrrhetinic acid),
short-chain fatty acids (
sodium butyrate),
indoles (indole-3-carbinol), isoflavonoids (
quercetin,
silymarin,
genistein), catechins ((-)-
epigallocatechin gallate (EGCG)), simple
phenols (
ellagic acid,
resveratrol,
piceatannol,
curcumin), pharmaceutical agents (
piroxicam,
acetylsalicylic acid,
tamoxifen), and
vitamins/derivatives (
ascorbic acid,
Trolox). We confirmed known chemopreventive mechanisms of these compounds. Additionally, we could demonstrate the usefulness of our approach by identification of hitherto unknown mechanisms of selected agents. As an example, we detected anti-inflammatory properties of
PEITC, based on
NF-kappaB-mediated inhibition of NO production. Further,
PEITC inhibited
phorbol ester-induced
superoxide anion radical production in granulocytes, and ODC induction in the 308 cell line. These mechanisms might contribute to the chemopreventive potential of
PEITC.