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Article

Antitumor, Immunomodulatory and Antiangiogenic Efficacy of Medicinal Mushroom Extract Mixtures in Advanced Colorectal Cancer Animal Model

1
Dr Myko San—Health from Mushrooms Co., Miramarska cesta 109, HR-10000 Zagreb, Croatia
2
Divison of Animal Physiology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, HR-10000 Zagreb, Croatia
3
Faculty of Health Studies, University of Rijeka, Ulica Viktora cara Emina 5, HR-51000 Rijeka, Croatia
*
Author to whom correspondence should be addressed.
Molecules 2020, 25(21), 5005; https://doi.org/10.3390/molecules25215005
Received: 24 September 2020 / Revised: 14 October 2020 / Accepted: 27 October 2020 / Published: 28 October 2020
(This article belongs to the Special Issue Translational Approach to Antitumor Drugs)
Due to frequent drug resistance and/or unwanted side-effects during conventional and targeted cancer treatments, development of multi-target therapies is an important research field. Medicinal mushrooms’ isolated specific compounds and mushroom extracts have been already proven as non-toxic multi-target inhibitors of specific oncogenic pathways, as well as potent immunomodulators. However, research on antitumor effects of multiple-species extract mixtures was limited so far. The aim of this study was therefore, a study of medicinal mushroom preparations AGARIKON.1 and AGARIKON PLUS on colorectal cell lines in vitro and colorectal mice model in vivo. We found a significant antiproliferative and pro-apoptotic effect of tested medicinal mushroom preparations on colorectal (HCT-116, SW620) tumor cell lines, while the effect on human fibroblast cell line (WI-38) was proliferative emphasizing a specificity towards tumor cell lines. We further investigated the effect of the medicinal mushroom preparations AGARIKON.1 and AGARIKON PLUS in various combinations with conventional cytostatic drug 5-fluorouracil in the advanced metastatic colorectal cancer mouse model CT26.WT. AGARIKON.1 and AGARIKON PLUS exhibited immunostimulatory and antiangiogenic properties in vivo which resulted in significantly increased survival and reduction in tumor volume. The antitumor effects of AGARIKON.1 and AGARIKON PLUS, with or without 5-fluorouracil, are based on M1 macrophage polarization enhancement, inhibition of M2 and tumor-associated macrophage (TAM) polarization, effects on T helper cell Th1/Th2/Th17 cytokine profiles, direct inhibition of CT26.WT tumor growth, inhibition of vascular endothelial growth factors (VEGF) and metalloproteinases 2 and 9 (MMP-2 and MMP-9) modulation. The administration of AGARIKON.1 and AGARIKON PLUS did not show genotoxic effect. This data provides good basis for an expanded translational study. View Full-Text
Keywords: colorectal cancer; medicinal mushrooms; immunotherapy; multi-target; combination therapy; 5-fluorouracil; survival; angiogenesis; macrophage polarization colorectal cancer; medicinal mushrooms; immunotherapy; multi-target; combination therapy; 5-fluorouracil; survival; angiogenesis; macrophage polarization
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MDPI and ACS Style

Jakopovic, B.; Oršolić, N.; Kraljević Pavelić, S. Antitumor, Immunomodulatory and Antiangiogenic Efficacy of Medicinal Mushroom Extract Mixtures in Advanced Colorectal Cancer Animal Model. Molecules 2020, 25, 5005. https://doi.org/10.3390/molecules25215005

AMA Style

Jakopovic B, Oršolić N, Kraljević Pavelić S. Antitumor, Immunomodulatory and Antiangiogenic Efficacy of Medicinal Mushroom Extract Mixtures in Advanced Colorectal Cancer Animal Model. Molecules. 2020; 25(21):5005. https://doi.org/10.3390/molecules25215005

Chicago/Turabian Style

Jakopovic, Boris, Nada Oršolić, and Sandra Kraljević Pavelić. 2020. "Antitumor, Immunomodulatory and Antiangiogenic Efficacy of Medicinal Mushroom Extract Mixtures in Advanced Colorectal Cancer Animal Model" Molecules 25, no. 21: 5005. https://doi.org/10.3390/molecules25215005

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