Identification and evaluation of novel potential cancer chemopreventive agents

Scheme of multistage carcinogenesis (left) and mechanisms of cancer chemoprevention (right)

Carcinogenesis can be regarded as an accumulation of genetic or biochemical cell damage, which offers a variety of targets for chemopreventive agents to prevent or inhibit the slow progression from early genetic lesions to tumor development.

Well established molecular mechanisms of chemoprevention include modulation of drug metabolism, anti-oxidant, radical-scavenging, anti-inflammatory, anti-tumor promoting and anti-proliferative activities as well as induction of terminal cell differentiation and apoptosis.

Knowledge of molecular mechanisms is of importance for safe application of known, but also for further development of novel potential cancer preventive agents.

Consequently, we have set up a battery of cell- and enzyme-based in vitro marker systems relevant for inhibition of carcinogenesis in vivo. These test systems offer fast (within days), sensitive and inexpensive identification and evaluation of lead compounds for the development of effective chemopreventive agents and the elucidation of their modes of action [Gerhauser et al., 2003]. Mechanisms are targeted at all stages of carcinogenesis and include modulation of xenobiotic metabolism, determination of radical-scavenging and anti-oxidant effects, inhibition of tumor promotion through anti-inflammatory and anti-hormonal mechanisms, inhibition of cell proliferation by induction of cell cycle arrest and apoptosis, and anti-angiogenic effects.

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