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The Agaricus blazei-Based Mushroom Extract, Andosan(™), Protects against Intestinal Tumorigenesis in the A/J Min/+ Mouse

BACKGROUND: The novel A/J Min/+ mouse, which is a model for human Familial Adenomatous Polyposis (FAP), develops spontaneously multiple adenocarcinomas in the colon as well as in the small intestine. Agaricus blazei Murill (AbM) is an edible Basidiomycetes mushroom that has been used in traditional...

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Autores principales: Hetland, Geir, Eide, Dag M., Tangen, Jon M., Haugen, Mads H., Mirlashari, Mohammad R., Paulsen, Jan E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5176274/
https://www.ncbi.nlm.nih.gov/pubmed/28002446
http://dx.doi.org/10.1371/journal.pone.0167754
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author Hetland, Geir
Eide, Dag M.
Tangen, Jon M.
Haugen, Mads H.
Mirlashari, Mohammad R.
Paulsen, Jan E.
author_facet Hetland, Geir
Eide, Dag M.
Tangen, Jon M.
Haugen, Mads H.
Mirlashari, Mohammad R.
Paulsen, Jan E.
author_sort Hetland, Geir
collection PubMed
description BACKGROUND: The novel A/J Min/+ mouse, which is a model for human Familial Adenomatous Polyposis (FAP), develops spontaneously multiple adenocarcinomas in the colon as well as in the small intestine. Agaricus blazei Murill (AbM) is an edible Basidiomycetes mushroom that has been used in traditional medicine against cancer and other diseases. The mushroom contains immunomodulating β-glucans and is shown to have antitumor effects in murine cancer models. Andosan(™) is a water extract based on AbM (82%), but it also contains the medicinal Basidiomycetes mushrooms Hericeum erinaceus and Grifola frondosa. METHODS AND FINDINGS: Tap water with 10% Andosan(™) was provided as the only drinking water for 15 or 22 weeks to A/J Min/+ mice and A/J wild-type mice (one single-nucleotide polymorphism (SNP) difference), which then were exsanguinated and their intestines preserved in formaldehyde and the serum frozen. The intestines were examined blindly by microscopy and also stained for the tumor-associated protease, legumain. Serum cytokines (pro- and anti-inflammatory, Th1-, Th2 -and Th17 type) were measured by Luminex multiplex analysis. Andosan(™) treated A/J Min/+ mice had a significantly lower number of adenocarcinomas in the intestines, as well as a 60% significantly reduced intestinal tumor load (number of tumors x size) compared to control. There was also reduced legumain expression in intestines from Andosan(™) treated animals. Moreover, Andosan(™) had a significant cytotoxic effect correlating with apoptosis on the human cancer colon cell line, Caco-2, in vitro. When examining serum from both A/J Min/+ and wild type mice, there was a significant increase in anti-tumor Th1 type and pro-inflammatory cytokines in the Andosan(™) treated mice. CONCLUSIONS: The results from this mouse model for colorectal cancer shows significant protection of orally administered Andosan(™) against development of intestinal cancer. This is supported by the finding of less legumain in intestines of Andosan(™) treated mice and increased systemic Th1 cytokine response. The mechanism is probably both immuno-modulatory and growth inhibition of tumor cells by induction of apoptosis.
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spelling pubmed-51762742017-01-04 The Agaricus blazei-Based Mushroom Extract, Andosan(™), Protects against Intestinal Tumorigenesis in the A/J Min/+ Mouse Hetland, Geir Eide, Dag M. Tangen, Jon M. Haugen, Mads H. Mirlashari, Mohammad R. Paulsen, Jan E. PLoS One Research Article BACKGROUND: The novel A/J Min/+ mouse, which is a model for human Familial Adenomatous Polyposis (FAP), develops spontaneously multiple adenocarcinomas in the colon as well as in the small intestine. Agaricus blazei Murill (AbM) is an edible Basidiomycetes mushroom that has been used in traditional medicine against cancer and other diseases. The mushroom contains immunomodulating β-glucans and is shown to have antitumor effects in murine cancer models. Andosan(™) is a water extract based on AbM (82%), but it also contains the medicinal Basidiomycetes mushrooms Hericeum erinaceus and Grifola frondosa. METHODS AND FINDINGS: Tap water with 10% Andosan(™) was provided as the only drinking water for 15 or 22 weeks to A/J Min/+ mice and A/J wild-type mice (one single-nucleotide polymorphism (SNP) difference), which then were exsanguinated and their intestines preserved in formaldehyde and the serum frozen. The intestines were examined blindly by microscopy and also stained for the tumor-associated protease, legumain. Serum cytokines (pro- and anti-inflammatory, Th1-, Th2 -and Th17 type) were measured by Luminex multiplex analysis. Andosan(™) treated A/J Min/+ mice had a significantly lower number of adenocarcinomas in the intestines, as well as a 60% significantly reduced intestinal tumor load (number of tumors x size) compared to control. There was also reduced legumain expression in intestines from Andosan(™) treated animals. Moreover, Andosan(™) had a significant cytotoxic effect correlating with apoptosis on the human cancer colon cell line, Caco-2, in vitro. When examining serum from both A/J Min/+ and wild type mice, there was a significant increase in anti-tumor Th1 type and pro-inflammatory cytokines in the Andosan(™) treated mice. CONCLUSIONS: The results from this mouse model for colorectal cancer shows significant protection of orally administered Andosan(™) against development of intestinal cancer. This is supported by the finding of less legumain in intestines of Andosan(™) treated mice and increased systemic Th1 cytokine response. The mechanism is probably both immuno-modulatory and growth inhibition of tumor cells by induction of apoptosis. Public Library of Science 2016-12-21 /pmc/articles/PMC5176274/ /pubmed/28002446 http://dx.doi.org/10.1371/journal.pone.0167754 Text en © 2016 Hetland 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hetland, Geir
Eide, Dag M.
Tangen, Jon M.
Haugen, Mads H.
Mirlashari, Mohammad R.
Paulsen, Jan E.
The Agaricus blazei-Based Mushroom Extract, Andosan(™), Protects against Intestinal Tumorigenesis in the A/J Min/+ Mouse
title The Agaricus blazei-Based Mushroom Extract, Andosan(™), Protects against Intestinal Tumorigenesis in the A/J Min/+ Mouse
title_full The Agaricus blazei-Based Mushroom Extract, Andosan(™), Protects against Intestinal Tumorigenesis in the A/J Min/+ Mouse
title_fullStr The Agaricus blazei-Based Mushroom Extract, Andosan(™), Protects against Intestinal Tumorigenesis in the A/J Min/+ Mouse
title_full_unstemmed The Agaricus blazei-Based Mushroom Extract, Andosan(™), Protects against Intestinal Tumorigenesis in the A/J Min/+ Mouse
title_short The Agaricus blazei-Based Mushroom Extract, Andosan(™), Protects against Intestinal Tumorigenesis in the A/J Min/+ Mouse
title_sort agaricus blazei-based mushroom extract, andosan(™), protects against intestinal tumorigenesis in the a/j min/+ mouse
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5176274/
https://www.ncbi.nlm.nih.gov/pubmed/28002446
http://dx.doi.org/10.1371/journal.pone.0167754
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