| Apigenin and naringenin suppress colon carcinogenesis through the aberrant crypt stage in azoxymethane-treated rats. | |
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MedLine Citation:
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PMID: 20511675 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Epidemiological evidence suggests that a diet abundant in fruits and vegetables may protect against colon cancer. Bioactive compounds, including flavonoids and limonoids, have been shown to possess antiproliferative and antitumorigenic effects in various cancer models. This experiment investigated the effects of four citrus flavonoids and one limonoid mixture at the promotion stage of chemically induced colon cancer in rats. Male Sprague-Dawley rats (n = 10 rats/group) were randomly allocated to one of six diets formulated to contain 0.1% apigenin, 0.02% naringenin, 0.1% hesperidin, 0.01% nobiletin, 0.035% limonin glucoside/obacunone glucoside mixture or a control diet (0% flavonoid/limonoid). Rats received experimental diets for 10 weeks and were injected with azoxymethane (15 mg/kg) at weeks 3 and 4. Excised colons were evaluated for aberrant crypt foci (ACF) formation, colonocyte proliferation (proliferating cell nuclear antigen assay), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling assay) and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) (immunoblotting). When compared with the control diet, apigenin lowered the number of high multiplicity ACF (HMACF >4 aberrant crypts/focus) by 57% (P < 0.05), while naringenin lowered both the number of HMACF by 51% (P < 0.05) and the proliferative index by 32% (P < 0.05). Both apigenin and naringenin increased apoptosis of luminal surface colonocytes (78% and 97%, respectively; P < 0.05) when compared with the control diet. Hesperidin, nobiletin and the limonin glucoside/obacunone glucoside mixture did not affect these variables. The colonic mucosal protein levels of iNOS or COX-2 were not different among the six diet groups. The ability of dietary apigenin and naringenin to reduce HMACF, lower proliferation (naringenin only) and increase apoptosis may contribute toward colon cancer prevention. However, these effects were not due to mitigation of iNOS and COX-2 protein levels at the ACF stage of colon cancer. |
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Authors:
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Tety Leonardi; Jairam Vanamala; Stella S Taddeo; Laurie A Davidson; Mary E Murphy; Bhimanagouda S Patil; Naisyin Wang; Raymond J Carroll; Robert S Chapkin; Joanne R Lupton; Nancy D Turner |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Experimental biology and medicine (Maywood, N.J.) Volume: 235 ISSN: 1535-3699 ISO Abbreviation: Exp. Biol. Med. (Maywood) Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-31 Completed Date: 2010-06-15 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 100973463 Medline TA: Exp Biol Med (Maywood) Country: England |
Other Details:
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Languages: eng Pagination: 710-7 Citation Subset: IM |
Affiliation:
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Faculty of Nutrition, Texas A&M University, College Station, TX 77843-3143, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents / administration & dosage*, pharmacology Apigenin / administration & dosage*, pharmacology Apoptosis Azoxymethane / toxicity* Blotting, Western Cell Proliferation Citrus / chemistry Colon / pathology Colonic Neoplasms / chemically induced*, prevention & control* Cyclooxygenase 2 / biosynthesis Diet / methods Flavanones / administration & dosage*, pharmacology Histocytochemistry Male Nitric Oxide Synthase Type II / biosynthesis Rats Rats, Sprague-Dawley |
| Grant Support | |
ID/Acronym/Agency:
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P30 ES009106-08/ES/NIEHS NIH HHS; P30-ES09106/ES/NIEHS NIH HHS; R37 CA057030-20/CA/NCI NIH HHS; R37 CA057030-23/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Flavanones; 25843-45-2/Azoxymethane; 480-41-1/naringenin; 520-36-5/Apigenin; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos2 protein, rat; EC 1.14.99.-/Ptgs2 protein, mouse; EC 1.14.99.1/Cyclooxygenase 2 |
| Comments/Corrections | |
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