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 35 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.

From a Medicinal Mushroom Blend a Direct Anticancer Effect on Triple-Negative Breast Cancer: A Preclinical Study on Lung Metastases

“…For the syngeneic tumor-bearing mice (4T1 and 4T1 M. U-care) generation see the work in [36]. The syngeneic tumor-bearing mice (4T1 and 4T1 M. U-care) were generated by injecting 1 × 10 6 of the 4T1 cells into the nape of the neck of the female Balb/C mice.…”

“…Immunohistochemical labeling extent evaluation was previously described in detail [36]. The optical density (OD), intended as immunohistochemical intensity, was assessed in 30 cells/section per six slides/mouse.…”

“…In addition, based on the notion that proliferative activity of cancer cells is also a crucial prognostic marker in the tumor diagnosis, we investigated the role of Proliferating Cell Nuclear Antigen (PCNA), being a pivotal protein directly related to the degrees of tumor malignancy and diagnosis [38,39]. Figure 1 emphasizes the key outcomes of the present investigation and also summarizes some major results of our previous study (for details see the work in [36]).…”

Medicinal Properties and Bioactive Compounds from Wild Mushrooms Native to North America

“…A mushroom mixture named as Micotherapy U-care consisted of G. lucidum, Lentinula edodes, Agaricus blazei, Ophiocordyceps sinensis, and Grifola frondosa was orally administered in mice implanted with triple-negative breast cancer. The results showed reduced pulmonary metastases density as well as decreased expression of interleukin-6, NOS, and COX-2 [ 53 ]. In another study, the anticancer effect of β-glucans along with radiation therapy was evaluated against lung cancer.…”

Use of Zebrafish Embryo Assay to Evaluate Toxicity and Safety of Bioreactor-Grown Exopolysaccharides and Endopolysaccharides from European Ganoderma applanatum Mycelium for Future Aquaculture Applications

“…Over the past two decades, medicinal mushroom exopolysaccharides (EPS) and endopolysaccharide (ENS) have been increasingly exploited for human benefits including clinical trials [ 1 ], neurological protection [ 2 ], potent in vitro biological activities [ 3 ], chicken patty [ 4 ], anti-oral cancer [ 5 ], and breast cancer models [ 6 ]; however, there is still limited development as yet on their commercial use by the aquaculture industry. Development and exploitation of medicinal mushroom products has significant potential to improve farmed fish health, where appropriate innovation in fish feed and formulation potentially offers safe, affordable and future intensive sustainability needs [ 7 , 8 , 9 ].…”