Antitumoral and antimetastatic activity of Maitake D-Fraction in triple-negative breast cancer cells

Abstract

Triple-negative breast cancer (TNBC) is associated with poor prognosis, high local recurrence rate and high rate of metastasis compared with other breast cancer subtypes. In addition, TNBC lacks a targeted therapy. This scenario highlights the need for novel compounds with high potential for TNBC treatment. In this regard, natural products are important sources of anticancer drugs. D-Fraction, a proteoglucan extracted from the edible and medicinal mushroom Grifola frondosa (Maitake), is a dietary supplement that has been shown to exert both immunostimulatory and immune-independent antitumoral effects on some cancer types. However, its antitumoral potential in TNBC is unknown. Therefore, we employed TNBC cells to investigate if D-Fraction is able to attenuate their aggressive phenotype. We found that D-Fraction decreases MDA-MB-231 cell viability through apoptosis induction and reduces their metastatic potential. D-Fraction increases cell-cell adhesion by increasing E-cadherin protein levels and β-catenin membrane localization, and increases cell-substrate adhesion. D-Fraction also decreases cell motility by affecting actin cytoskeleton rearrangements, and proteolytic activity of MMP-2 and MMP-9. Furthermore, D-Fraction decreases the invasive capacity of MDA-MB-231 cells. In concordance, D-Fraction retards tumor growth and reduces lung metastases in a xenograft model. Altogether, these results suggest the potential therapeutic role of D-Fraction in aggressive TNBC.

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

“…We may hypothesize that the lower expression of IL-6 determined in M. U-care-treated mice would be related to a decrease in cancer cell proliferation, in which IL-6 could act on Bcl-2 expression, altering the proliferation/apoptosis balance toward neoplastic cell apoptosis. This hypothesis seems to be strongly corroborated by previous in vitro findings, using BC cell models exposed to G. frondosa and G. lucidum [9,12,30,56].…”

“…(Noceto, Parma, Italy) consisting of a mixture of mycelium and sporophores extracts of five species, including Agaricus blazei, Ophiocordyceps sinensis, Ganoderma lucidum, Grifola frondosa, and Lentinula edodes. Anti-cancer, onco-immunological, and immuno-modulating properties of these five medicinal mushrooms have been previously described in vitro [11,12] and in preclinical [13] and clinical study [8].…”

Medicinal Mushrooms: Bioactive Compounds, Use, and Clinical Trials

“…Not only did it activate macrophages, T cells, and NK cells, but it also triggered the expression of BCL2-antagonist/killer 1 (BAK-1) and several other genes (RASSF-2, FADD, IGFBP-7, ITGA2, ICAM3, SOD2, CAV-1, Cul-3, NRF2, Cycline E, ST7, and SPARC) involved in apoptotic stimulation, the inhibition of cell growth and proliferation and cell cycle arrest, the suppression of tumor cell migration and metastasis, and the downregulation of the PI3K-AKT signaling pathway. In a subsequent study in rodent LM3 mammary adenocarcinoma cells, it was observed that D-fraction, in addition to inducing apoptosis and reducing cell motility and invasiveness, increased cell adhesion by upregulating E-cadherin protein levels and inhibiting matrix metalloproteinase-2 (MMP-2) activity [ 39 ], while in triple-negative breast cancer (TNBC) cells, in addition to the effects just described, it also suppressed MMP-9 and reduced cell–cell adhesion by also increasing the membrane localization of the β-catenin protein [ 40 ].…”

Nucleus-enriched Ruthenium Polypyridine Complex Acts as a Potent Inhibitor to Suppress Triple-negative Breast Cancer Metastasis In vivo

“…Considering that metastasis is a severe risk in TNBC treatment, it is important to search for effective drugs that can inhibit it [ 24 ]. To investigate the anti-metastatic activity of the complexes, wound healing assay was performed to estimate cell migration and repair ability because the healing degree of scratches can reflect the inhibition effect of drugs on the migration ability of tumor cells.…”