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Novel Medicinal Mushroom Blend as a Promising Supplement in Integrative Oncology: A Multi-Tiered Study using 4T1 Triple-Negative Mouse Breast Cancer Model.

ABSTRACT: Although medicinal mushroom extracts have been proposed as promising anti-cancer agents, their precise impacts on metastatic breast cancer are still to be clarified. For this purpose, the present study exploited the effect of a novel medicinal mushroom blend, namely Micotherapy U-care, in a 4T1 triple-negative mouse breast cancer model. Mice were orally administered with Micotherapy U-care, consisting of a mixture of Agaricus blazei, Ophiocordyceps sinensis, Ganoderma lucidum, Grifola frondosa, and Lentinula edodes. The syngeneic tumor-bearing mice were generated by injecting 4T1 cells in both supplemented and non-supplemented mice. After sacrifice 25 days later, specific endpoints and pathological outcomes of the murine pulmonary tissue were evaluated. (i) Histopathological and ultrastructural analysis and (ii) immunohistochemical assessment of TGF-ß1, IL-6 and NOS2, COX2, SOD1 as markers of inflammation and oxidative stress were performed. The QoL was comparatively evaluated. Micotherapy U-care supplementation, starting before 4T1 injection and lasting until the end of the experiment, dramatically reduced the pulmonary metastases density, also triggering a decrease of fibrotic response, and reducing IL-6, NOS, and COX2 expression. SOD1 and TGF-ß1 results were also discussed. These findings support the valuable potential of Micotherapy U-care as adjuvant therapy in the critical management of triple-negative breast cancer.

SUBMITTER: Roda E

PROVIDER: S-EPMC7279026 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Novel Medicinal Mushroom Blend as a Promising Supplement in Integrative Oncology: A Multi-Tiered Study using 4T1 Triple-Negative Mouse Breast Cancer Model.

Roda Elisa E Luca Fabrizio De F Iorio Carmine Di CD Ratto Daniela D Siciliani Stella S Ferrari Beatrice B Cobelli Filippo F Borsci Giuseppina G Priori Erica Cecilia EC Chinosi Silvia S Ronchi Andrea A Franco Renato R Di Francia Raffaele R Berretta Massimiliano M Locatelli Carlo Alessandro CA Gregori Andrej A Savino Elena E Bottone Maria Grazia MG Rossi Paola P

International journal of molecular sciences 20200514 10

Although medicinal mushroom extracts have been proposed as promising anti-cancer agents, their precise impacts on metastatic breast cancer are still to be clarified. For this purpose, the present study exploited the effect of a novel medicinal mushroom blend, namely Micotherapy U-care, in a 4T1 triple-negative mouse breast cancer model. Mice were orally administered with Micotherapy U-care, consisting of a mixture of Agaricus blazei, Ophiocordyceps sinensis, ...[more]

PMID: 32423132

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Project description:Ganoderma lucidum is one of the well-known medicinal basidiomycetes worldwide. The mitochondrion, referred to as the second genome, is an organelle found in most eukaryotic cells and participates in critical cellular functions. Elucidating the structure and function of this genome is important to understand completely the genetic contents of G. lucidum. In this study, we assembled the mitochondrial genome of G. lucidum and analyzed the differential expressions of its encoded genes across three developmental stages. The mitochondrial genome is a typical circular DNA molecule of 60,630 bp with a GC content of 26.67%. Genome annotation identified genes that encode 15 conserved proteins, 27 tRNAs, small and large rRNAs, four homing endonucleases, and two hypothetical proteins. Except for genes encoding trnW and two hypothetical proteins, all genes were located on the positive strand. For the repeat structure analysis, eight forward, two inverted, and three tandem repeats were detected. A pair of fragments with a total length around 5.5 kb was found in both the nuclear and mitochondrial genomes, which suggests the possible transfer of DNA sequences between two genomes. RNA-Seq data for samples derived from three stages, namely, mycelia, primordia, and fruiting bodies, were mapped to the mitochondrial genome and qualified. The protein-coding genes were expressed higher in mycelia or primordial stages compared with those in the fruiting bodies. The rRNA abundances were significantly higher in all three stages. Two regions were transcribed but did not contain any identified protein or tRNA genes. Furthermore, three RNA-editing sites were detected. Genome synteny analysis showed that significant genome rearrangements occurred in the mitochondrial genomes. This study provides valuable information on the gene contents of the mitochondrial genome and their differential expressions at various developmental stages of G. lucidum. The results contribute to the understanding of the functions and evolution of fungal mitochondrial DNA.

Project description:It is known that many edible mushrooms have important medicinal properties, including effects on different types of cancers. This is the first report regarding the neuroprotective, antimicrobial, antioxidative and anticancer activities of the acetone extract of edible mushroom Hygrophorus eburneus. Neuroprotective potential was evaluated by measuring the capacity of the extract to inhibit acetylcholinesterase. In this assay, the tested extract showed activity against acetylcholinesterase in a dose-dependent manner where the percentage of inhibition ranged from 13.19 to 46.44 %. The antimicrobial potential was determined by the microdilution method against five species of bacteria and eight species of fungi and the results of this method exhibited moderate antimicrobial activity of H. eburneus with MIC values ranging from 6.25 to 25 mg/mL. Antioxidant activity was evaluated by measuring the scavenging capacity of the tested sample on DPPH and superoxide anion radicals, by the reducing power assay and by measuring the amounts of total phenolics in extract. As a result of the study, H. eburneus extract showed a potent antioxidant activity (IC50 were 102.93 μg/mL for DPPH radical scavenging activity and 123.27 μg/mL for superoxide anion radicals scavenging) while absorbances for reducing power assay were from 0.0235 to 0.1161. The total phenolic content in the extract was 9.27 µg PE/mg. Finally, anticancer effects were evaluated by MTT test for cytotoxicity, acridine orange/ethidium bromide staining for detection of the type of cell death and wound healing assay for antimigratory effects on human colorectal cancer cell line (HCT-116) and human breast cancer cell line (MDA-MB-231). The results for cytotoxicity and apoptosis were measured after 24 and 72 h and for anti-migratory effect after 12 and 24 h. The tested H. eburneus mushroom extract expressed cell selectivity, with notable cytotoxic effects observed on HCT-116 cells, with a strong proapoptotic potential. The migration of HCT-116 cells was significantly inhibited, while MDA-MB-231 cells were less sensitive to the treatment. The results of this study revealed that the tested extract had relatively strong neuroprotective, antimicrobial, antioxidant, and anticancer effects. It suggests that this mushroom can be proposed as a novel source of nutraceuticals and pharmaceuticals.

Dataset Information

Novel Medicinal Mushroom Blend as a Promising Supplement in Integrative Oncology: A Multi-Tiered Study using 4T1 Triple-Negative Mouse Breast Cancer Model.

Publications

Novel Medicinal Mushroom Blend as a Promising Supplement in Integrative Oncology: A Multi-Tiered Study using 4T1 Triple-Negative Mouse Breast Cancer Model.

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