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Metabolism of resveratrol and its hydroxymetabolites - impact on their anticancer properties

Ziel

Breast cancer is the major cause of cancer death in women worldwide, however significant geographical differences in morbidity can be observed. Studies of migrant populations have indicated that the genetic background only plays a tiny, if any, role in differences in breast cancer morbidity. The lower incidence of breast cancer in Asian population was associated with diet contents phytoestrogens.

Their potential health benefits include protection against hormone-dependent cancer, cardiovascular disease and osteoporosis. Resveratrol (3,4',5-trihydroxystilbene) has attracted considerable attention because its presence in diet and its wide spectrum of biological activity including antioxidative, antiplatelet, antifungal, phytoestrogenic, cardioprotective properties. Because of its structural similarity to diethylstilbestrol resveratrol can act as phytoestrogen. Many authors proposed this mechanism as explanation its action against breast cancer cells.

Moreover resveratrol acts as growth inhibitor of estrogen-independent cell lines. Piceatannol (3,3'4'5 trihydroxystilbene) is naturally occurring analog of resveratrol and as well as resveratrol has been classified as a phytoalexin. Many reports show that piceatannol interferes with neoplastic growth by modifying multiple cellular targets. While effects of resveratrol and piceatannol are well studied in various in vitro and animal models, up to now, little is known about their higher hydroxy analogs. Some findings suggest that they may be formed as the metabolites of resveratrol and piceatannol.

The main aims of this proposal are: estimation of cytotoxicity and apoptosis induction in estrogen receptor positive, negative and genetically transfected breast cancer cell lines by resveratrol analogs and investigation of metabolism of resveratrol analogs in these cell lines. Results will provide valuable information in design of new anticancer drugs as well as understanding and resolving problems of cancer drug resistance.

Wissenschaftliches Gebiet (EuroSciVoc)

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Aufforderung zur Vorschlagseinreichung

FP6-2002-MOBILITY-11
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Finanzierungsplan

ERG - Marie Curie actions-European Re-integration Grants

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DEPARTMENT OF TOXICOLOGY, FACULTY OF PHARMACY, POZNAN UNIVERSITY OF MEDICAL SCIENCES
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