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 <i>Grifola frondosa</i> (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 <i>viability</i> through <i>apoptosis</i> induction and reduces their metastatic potential. D-Fraction increases <i>cell-cell adhesion</i> by increasing E-cadherin protein levels and β-catenin membrane localization, and increases <i>cell-substrate adhesion</i>. D-Fraction also decreases cell <i>motility</i> by affecting actin cytoskeleton rearrangements, and <i>proteolytic activity</i> of MMP-2 and MMP-9. Furthermore, D-Fraction decreases the <i>invasive</i> capacity of MDA-MB-231 cells. In concordance, D-Fraction <i>retards tumor growth</i> and <i>reduces lung metastases</i> in a xenograft model. Altogether, these results suggest the potential therapeutic role of D-Fraction in aggressive TNBC.