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Inhibition of Intestinal Adenoma Formation in APC(Min/) (+) Mice by Riccardin D, a Natural Product Derived from Liverwort Plant Dumortiera hirsuta
BACKGROUND: Mutation of tumor suppressor gene, adenomatous polyposis coli (APC), is the primary molecular event in the development of most intestinal carcinomas. Animal model with APC gene mutation is an effective tool for study of preventive approaches against intestinal carcinomas. We aimed to eva...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303813/ https://www.ncbi.nlm.nih.gov/pubmed/22432006 http://dx.doi.org/10.1371/journal.pone.0033243 |
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author | Liu, Hui-Ping Gao, Zu-Hua Cui, Shu-Xiang Sun, De-Fu Wang, Yan Zhao, Cui-Rong Lou, Hong-Xiang Qu, Xian-Jun |
author_facet | Liu, Hui-Ping Gao, Zu-Hua Cui, Shu-Xiang Sun, De-Fu Wang, Yan Zhao, Cui-Rong Lou, Hong-Xiang Qu, Xian-Jun |
author_sort | Liu, Hui-Ping |
collection | PubMed |
description | BACKGROUND: Mutation of tumor suppressor gene, adenomatous polyposis coli (APC), is the primary molecular event in the development of most intestinal carcinomas. Animal model with APC gene mutation is an effective tool for study of preventive approaches against intestinal carcinomas. We aimed to evaluate the effect of Riccardin D, a macrocyclic bisbibenzyl compound, as a chemopreventive agent against intestinal adenoma formation in APC(Min/+) mice. METHODS: APC(Min/+) mice were given Riccardin D by p.o. gavage for 7 weeks. Mice were sacrificed, and the number, size and histopathology of intestinal polyps were examined under a microscope. We performed immunohistochemical staining, western blotting, reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) in intestinal polyps to investigate the mechanism of chemopreventive effect of Riccardin D. RESULTS: Riccardin D treatment resulted in a significant inhibition of intestinal adenoma formation, showing a reduction of polyp number by 41.7%, 31.1% and 44.4%, respectively, in proximal, middle and distal portions of small intestine. The activity of Riccardin D against polyp formation was more profound in colon, wherein Riccardin D decreased polyp number by 79.3%. Size distribution analysis revealed a significant reduction in large-size polyps (2–3 mm) by 40.0%, 42.5% and 33.3%, respectively, in proximal, middle and distal portions of small intestine, and 77.8% in colon. Histopathological analysis of the intestinal polyps revealed mostly hyperplastic morphology without obvious dysplasia in Riccardin D-treated mice. Molecular analyses of the polyps suggested that the inhibitory effect of Riccardin D on intestinal adenoma formation was associated with its abilities of reduction in cell proliferation, induction of apoptosis, antiangiogenesis, inhibition of the Wnt signaling pathway and suppression of inflammatory mediators in polyps. CONCLUSIONS: Our results suggested that Riccardin D exerts its chemopreventive effect against intestinal adenoma formation through multiple mechanisms including anti-proliferative, apoptotic, anti-angiogenic and anti-inflammatory activity. |
format | Online Article Text |
id | pubmed-3303813 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33038132012-03-19 Inhibition of Intestinal Adenoma Formation in APC(Min/) (+) Mice by Riccardin D, a Natural Product Derived from Liverwort Plant Dumortiera hirsuta Liu, Hui-Ping Gao, Zu-Hua Cui, Shu-Xiang Sun, De-Fu Wang, Yan Zhao, Cui-Rong Lou, Hong-Xiang Qu, Xian-Jun PLoS One Research Article BACKGROUND: Mutation of tumor suppressor gene, adenomatous polyposis coli (APC), is the primary molecular event in the development of most intestinal carcinomas. Animal model with APC gene mutation is an effective tool for study of preventive approaches against intestinal carcinomas. We aimed to evaluate the effect of Riccardin D, a macrocyclic bisbibenzyl compound, as a chemopreventive agent against intestinal adenoma formation in APC(Min/+) mice. METHODS: APC(Min/+) mice were given Riccardin D by p.o. gavage for 7 weeks. Mice were sacrificed, and the number, size and histopathology of intestinal polyps were examined under a microscope. We performed immunohistochemical staining, western blotting, reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) in intestinal polyps to investigate the mechanism of chemopreventive effect of Riccardin D. RESULTS: Riccardin D treatment resulted in a significant inhibition of intestinal adenoma formation, showing a reduction of polyp number by 41.7%, 31.1% and 44.4%, respectively, in proximal, middle and distal portions of small intestine. The activity of Riccardin D against polyp formation was more profound in colon, wherein Riccardin D decreased polyp number by 79.3%. Size distribution analysis revealed a significant reduction in large-size polyps (2–3 mm) by 40.0%, 42.5% and 33.3%, respectively, in proximal, middle and distal portions of small intestine, and 77.8% in colon. Histopathological analysis of the intestinal polyps revealed mostly hyperplastic morphology without obvious dysplasia in Riccardin D-treated mice. Molecular analyses of the polyps suggested that the inhibitory effect of Riccardin D on intestinal adenoma formation was associated with its abilities of reduction in cell proliferation, induction of apoptosis, antiangiogenesis, inhibition of the Wnt signaling pathway and suppression of inflammatory mediators in polyps. CONCLUSIONS: Our results suggested that Riccardin D exerts its chemopreventive effect against intestinal adenoma formation through multiple mechanisms including anti-proliferative, apoptotic, anti-angiogenic and anti-inflammatory activity. Public Library of Science 2012-03-14 /pmc/articles/PMC3303813/ /pubmed/22432006 http://dx.doi.org/10.1371/journal.pone.0033243 Text en Liu et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Liu, Hui-Ping Gao, Zu-Hua Cui, Shu-Xiang Sun, De-Fu Wang, Yan Zhao, Cui-Rong Lou, Hong-Xiang Qu, Xian-Jun Inhibition of Intestinal Adenoma Formation in APC(Min/) (+) Mice by Riccardin D, a Natural Product Derived from Liverwort Plant Dumortiera hirsuta |
title | Inhibition of Intestinal Adenoma Formation in APC(Min/)
(+) Mice by Riccardin D, a Natural Product Derived from Liverwort Plant Dumortiera hirsuta
|
title_full | Inhibition of Intestinal Adenoma Formation in APC(Min/)
(+) Mice by Riccardin D, a Natural Product Derived from Liverwort Plant Dumortiera hirsuta
|
title_fullStr | Inhibition of Intestinal Adenoma Formation in APC(Min/)
(+) Mice by Riccardin D, a Natural Product Derived from Liverwort Plant Dumortiera hirsuta
|
title_full_unstemmed | Inhibition of Intestinal Adenoma Formation in APC(Min/)
(+) Mice by Riccardin D, a Natural Product Derived from Liverwort Plant Dumortiera hirsuta
|
title_short | Inhibition of Intestinal Adenoma Formation in APC(Min/)
(+) Mice by Riccardin D, a Natural Product Derived from Liverwort Plant Dumortiera hirsuta
|
title_sort | inhibition of intestinal adenoma formation in apc(min/)
(+) mice by riccardin d, a natural product derived from liverwort plant dumortiera hirsuta |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303813/ https://www.ncbi.nlm.nih.gov/pubmed/22432006 http://dx.doi.org/10.1371/journal.pone.0033243 |
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