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The effects of blended medicinal mushroom extracts with or without 5-fluorouracil on survival and various antitumor parameters in mouse CT26.WT colon cancer

Medicinal mushrooms are for millennia widely appreciated as natural sources of bioactive substances and are recognized as significant immunomodulatory and antitumor agents. In the last 50 years there has been an increased interest in the use of fungi in the (traditional) medicine as well as in determining their therapeutic and medicinal properties, resulting in exponential growth of the number of scientific research papers on their impact on animal and human organism. This paper describes the effects of two commercial preparations from medicinal mushrooms, tableted preparation AGARIKON.1® and liquid preparation AGARIKON PLUS® (manufacturer: Dr Myko San – Health from Mushrooms). These extract preparations from various mushroom species with proven antitumor effects were compared in various combinations, with or without 5-fluorouracil (5-FU), which is a common antimetabolite class drug used in treating colon cancer. An important hypothesis throughout is that the blend of different medicinal mushroom substances of the same class of compounds achieved synergistic effects, and consequently significantly stronger cytotoxic and other effects. The preparations AGARIKON.1® and AGARIKON PLUS® differ significantly in their polysaccharide to polyphenol contents ratio which differentiates their immunological and antimetastatic effects. We have simulated an advanced disease model by starting with the therapy late in the course of the disease. Two models of experimental design in studying survival were used: curative and preventative. Besides observed effects on survival, we also recorded the effects of mushroom preparations with or without cytostatic drug on angiogenesis and tumor invasiveness by measuring MMP-2, MMP-9 and VEGF levels, as well as immunological parameters such as macrophage polarization by measuring NO, arginase levels, as well as by using Th1/Th2/Th17 cytokine panels. Additionally, we have observed direct cytotoxic effects of mushroom preparations on human colorectal cell lines using MTT assay and proved their apoptosis inducing properties by flow cytometry. The results show significant beneficial effects on various parameters related to tumor suppression and show that medicinal mushrooms preparations alone and in combination with standard therapies have a major role in this in vivo model of colorectal cancer, which should be further explored in the clinic.

medicinal mushrooms, polysaccharides ; colon cancer ; immunomodulation ; metastasis

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