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

PLoS One. 2016 Dec 21;11(12):e0167754. doi: 10.1371/journal.pone.0167754. eCollection 2016.

Abstract

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.

MeSH terms

  • Agaricus / chemistry*
  • Agaricus / metabolism
  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects
  • Caco-2 Cells
  • Cysteine Endopeptidases / metabolism
  • Cytokines / blood
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Intestinal Mucosa / metabolism*
  • Intestines / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Plant Extracts / chemistry*
  • Plant Extracts / pharmacology
  • Protective Agents / chemistry*
  • Protective Agents / pharmacology

Substances

  • Antineoplastic Agents, Phytogenic
  • Cytokines
  • Plant Extracts
  • Protective Agents
  • Cysteine Endopeptidases
  • asparaginylendopeptidase

Grant support

The authors received no specific funding for this work, except for Andosan that was provided free of charge for the study from the Norwegian company Immunopharma.