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EDRI Federal Project Inventory:
61764-03 Anticarcinogenic Effects and Mechanisms of Genistein
- Sponsor Organization: NIH/NCI
- Project Title: 61764-03 ANTICARCINOGENIC EFFECTS AND MECHANISMS OF GENISTEIN
- Project Focus: HUMAN HEALTH EFFECTS
- Description: Epidemiological studies suggest an inverse correlation between soyfood
consumption and human cancer mortality.Laboratory studies indicate
that soy diets also inhibit experimentally induced animal tumors.
Although most studiesattribute the anticarcinogenic effect of soybeans
to the protease inhibitors, increasing evidence suggests that
isoflavones,non-protein components richly present in soybeans, may
also play important roles. Genistein, one of the major
soybeanisoflavones, has been shown to inhibit tyrosine protein kinase
(TPK), DNA topoisomerase II (Topo Il), and ribosomalS6 kinase (RS6K),
suppress tumor cell growth, and induce differentiation of several
malignant cell lines. Ourpreliminary studies have shown that
genistein suppresses 7,12-dimethylbenz[a]anthracene (DMBA)-induced
DNAadduct formation and DNA oxidation, and inhibits 12-O-
tetradecanoyl phorbol-13-acetate (TPA)-induced H2O2formation,
inflammatory responses, and proto-oncogene expression in vivo.
However, whether genistein modifieschemical carcinogenesis in vivo
remains unclear. This proposal is designed to test the hypothesis that
genistein inhibitsoxidative DNA damage induced by carcinogenic agents
and further modifies the initiational, promotional, andprogressional
processes of chemical carcinogenesis. The overall objective is to
determine if genistein modifies theinitiation- and promotion-related
biochemical events and subsequently inhibits skin tumor formation in
vivo. The initialaim of the project is to determine if topical
application of genistein modifies the initiation- and promotion-
related eventswith an emphasis on oxidative DNA damage. The second aim
is to determine if topical application of genistein affectsinitiation,
promotion and/or progression of multistage skin carcinogenesis.
Finally, we will determine if dietaryadministration of genistein
modulates these carcinogenic processes in the multistage
carcinogenesis model. If, in fact,genistein has anticarcinogenic
effects, an elucidation of the mechanisms of genistein's action will
contribute toapplication of this soybean isoflavone in prevention
and/or therapy of human cancers.
- References:
- Category: MODELS
- Subcategory: BASIC RESEARCH
- Keywords for Experimental System/Species: LABORATORY STUDY, MAMMALIAN
- Keywords for Experimental Endpoints: CARCINOGENESIS, GENE EXPRESSION, GROWTH
- Chemical Agents: SOY, ISOFLAVONE, GENISTEIN, PHYTOESTROGENS
- Performing Institution: MOUNT SINAI MEDICAL CENTER
- Contact: CONTRACT PERSON: ELAINE C. LEE; BUILDING 31; 11A21; NATIONAL CANCER
INSTITUTE, NIH,BETHESDA, MD 20892-2590; 301-496-5515;
LEEE@OD.NCI.NIH.GOV
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