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INSTITUT FÜR
TOXIKOLOGIE


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WÄTJEN


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1427


GRK-PROJEKT-2

GRK-PROJEKT-6

TOXIKOLOGIE VON
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ERGÄNZUNGSSTOFFEN


MYKOTOXINE

ANTI-TUMOR-
SUBSTANZEN AUS
TRAD. HEILPFLANZEN


ANTI-TUMOR-
SUBSTANZEN AUS
MARINEN
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SCHWERMETALL-
TOXIKOLOGIE



Projekt ANTI-TUMOR-SUBSTANZEN AUS TRADITIONELLEN HEILPFLANZEN

The genus Erythrina (Leguminosae), consisting of over 100 different species, is distributed in tropical regions. In traditional medicine, Erythrina species are used to treat cancer, but little is known about the anticancer mechanisms. From the stem bark of Erythrina addisoniae Hutch. & Dalziel, six prenylated pterocarpanes were isolated and analysed for pharmacological activity: While calopocarpin, cristacarpin, orientanol c and isoneorautenol showed only a weak or moderate toxicity in H4IIE cells (EC50-value > 25 µM), the toxicity of neorautenol and phaseollin was in the low micromolar range cells (EC50-value: 1 and 1.5 µM, respectively). We further focused on these two substances showing that both increased caspase 3/7 activity and nuclear fragmentation as markers for apoptotic cell death. Neorautenol (10 µM, 2 h), but not phaseollin induced the formation of DNA strand breaks (comet assay). Both substances (10 µM, 2 h) decreased the activation of the ERK MAP kinase (p44/p42) which is associated with cell proliferation. Analysing HepG2 human hepatoma cells phaseollin and neorautenol showed similar results. We conclude that the pterocarpanes phaseollin and neorautenol may be responsible for the anticarcinogenic actions of the plant extract reported in the literature. Further analysis of these substances may lead to new pharmacons to be used in cancer therapy.

 

structures of isolated pterocarpans

The genus Erythrina (Leguminosae), a group of more than 100 different species, is distributed in all tropical areas of the world (Krukof and Barneby, 1974). These plant species are widely used in folk medicine to treat diverse diseases, e.g. different kinds of infections as well as inflammation of skin and mucous membranes (Ghosal et al., 1972; Cox, 1993; Saiduh et al., 2000). They are also used due to their analgesic as well as tranquilizing and sedative activities (Ghosal et al., 1972; Burkill, 1995; Garin-Aguilar et al., 2000). Erythrina species are also used against cancer, e.g. stomach cancer in folk medicine (Hartwell, 1970). In spite of this therapeutic use, little is known about the anticancer mechanisms because only few investigations on cellular level have been conducted.

Erythrina addisoniae Hutch. & Dalziel occurs in tropical areas of Ghana and other West-African countries. Its stem and root bark is mainly used against dysentery, hepatitis, rheumatic disorders and pain (Burkill, 1995). In some areas of Ghana E. addisoniae is also used against swellings and cancer (Hartwell, 1970). Revently, we isolated six pterocarpanes (neorautenol, phaseollin, calopocarpin, isoneorautenol, orientanol c  and cristacarpin) from the stem bark of Erythrina addisoniae (Suckow-Schnitker et al., submitted). Here we analyse pharmacological effects (e.g. cytotoxic and pro-apoptotic effects) of the isolated compounds in different cancer cell lines to elucidate anticancer effects of the substances.

 

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