| Berries and ellagic acid prevent estrogen-induced mammary tumorigenesis by modulating enzymes of estrogen metabolism. | |
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MedLine Citation:
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PMID: 20501861 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To determine whether dietary berries and ellagic acid prevent 17beta-estradiol (E(2))-induced mammary tumors by altering estrogen metabolism, we randomized August-Copenhagen Irish rats (n = 6 per group) into five groups: sham implant + control diet, E(2) implant + control diet (E(2)-CD), E(2) + 2.5% black raspberry (E(2)-BRB), E(2) + 2.5% blueberry (E(2)-BB), and E(2) + 400 ppm ellagic acid (E(2)-EA). Animals were euthanized at early (6 wk), intermediate (18 wk), and late (24 wk) phases of E(2) carcinogenesis, and the mammary tissue was analyzed for gene expression changes using quantitative real-time PCR. At 6 weeks, E(2) treatment caused a 48-fold increase in cytochrome P450 1A1 (CYP1A1; P < 0.0001), which was attenuated by both BRB and BB diets to 12- and 21-fold, respectively (P < 0.001). E(2) did not alter CYP1B1 levels, but both berry and EA diets significantly suppressed it by 11- and 3.5-fold, respectively, from baseline (P < 0.05). There was a 5-fold increase in 17beta-hydroxysteroid dehydrogenase 7 (17betaHSD7), and this was moderately abrogated to approximately 2-fold by all supplementation (P < 0.05). At 18 weeks, CYP1A1 was elevated by 15-fold in E(2)-CD and only E(2)-BB reduced this increase to 7-fold (P < 0.05). Catechol-O-methyltransferase expression was elevated 2-fold by E(2) treatment (P < 0.05), and all supplementation reversed this. At 24 weeks, CYP1A1 expression was less pronounced but still high (8-fold) in E(2)-treated rats. This increase was reduced to 3.2- and 4.6-fold by E(2)-BRB and E(2)-EA, respectively (P < 0.05), but not by E(2)-BB. Supplementation did not alter the effect of E(2) on steroid receptors. The diets also significantly suppressed mammary tumor incidence (10-30%), volume (41-67%), and multiplicity (38-51%; P < 0.05). Berries may prevent mammary tumors by suppressing the levels of E(2)-metabolizing enzymes during the early phase of E(2) carcinogenesis. |
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Authors:
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Harini S Aiyer; Ramesh C Gupta |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Date: 2010-05-25 |
Journal Detail:
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Title: Cancer prevention research (Philadelphia, Pa.) Volume: 3 ISSN: 1940-6215 ISO Abbreviation: Cancer Prev Res (Phila) Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-04 Completed Date: 2010-09-30 Revised Date: 2012-01-24 |
Medline Journal Info:
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Nlm Unique ID: 101479409 Medline TA: Cancer Prev Res (Phila) Country: United States |
Other Details:
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Languages: eng Pagination: 727-37 Citation Subset: IM |
Copyright Information:
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2010 AACR. |
Affiliation:
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James Graham Brown Cancer Center, University of Louisville, KY 40202, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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17-Hydroxysteroid Dehydrogenases
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biosynthesis,
genetics Animals Aryl Hydrocarbon Hydroxylases / biosynthesis, genetics Blueberry Plant* Catechol O-Methyltransferase / biosynthesis, genetics Cell Transformation, Neoplastic Cytochrome P-450 CYP1A1 / biosynthesis, genetics Drug Screening Assays, Antitumor Ellagic Acid / pharmacology, therapeutic use* Estrogens / metabolism* Female Fruit Glutathione Transferase / biosynthesis, genetics Isoenzymes / biosynthesis, genetics Mammary Neoplasms, Experimental / enzymology, prevention & control* Neoplasms, Hormone-Dependent / enzymology, prevention & control* Phytotherapy* Random Allocation Rats Rats, Inbred Strains Receptors, Estrogen / biosynthesis, genetics Receptors, Progesterone / biosynthesis, genetics Rosaceae* |
| Grant Support | |
ID/Acronym/Agency:
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CA-118114/CA/NCI NIH HHS; CA-90892/CA/NCI NIH HHS; R01 CA090892-01A1/CA/NCI NIH HHS; R01 CA090892-02/CA/NCI NIH HHS; R01 CA090892-03/CA/NCI NIH HHS; R01 CA090892-04/CA/NCI NIH HHS; R01 CA090892-05/CA/NCI NIH HHS; R01 CA118114-01A2/CA/NCI NIH HHS; R01 CA118114-02/CA/NCI NIH HHS; R01 CA118114-03/CA/NCI NIH HHS; R01 CA125152-05/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Estrogens; 0/Isoenzymes; 0/Receptors, Estrogen; 0/Receptors, Progesterone; 476-66-4/Ellagic Acid; EC 1.1.-/17-Hydroxysteroid Dehydrogenases; EC 1.1.1.51/3 (or 17)-beta-hydroxysteroid dehydrogenase; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/Cytochrome P-450 CYP1A1; EC 1.14.14.1/cytochrome P450, family 1, subfamily B, polypeptide 1; EC 2.1.1.6/Catechol O-Methyltransferase; EC 2.5.1.18/Glutathione Transferase; EC 2.5.1.18/glutathione S-transferase M1; EC 2.5.1.18/glutathione S-transferase alpha |
| Comments/Corrections | |
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