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

// Eliana Noelia Alonso 1, * , María Julia Ferronato 1, * , María Eugenia Fermento 1 , Norberto Ariel Gandini 1 , Alejandro López Romero 2 , Josefina Alejandra Guevara 1 , María Marta Facchinetti 1 and Alejandro Carlos Curino 1 1 Laboratorio de Biología del Cáncer, Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Universidad Nacional del Sur (UNS)–CONICET, Departamento de Biología, Bioquímica y Farmacia (UNS), Bahía Blanca, Argentina 2 Departamento de Hematología, IACA Laboratorios, Bahía Blanca, Argentina * These authors contributed equally to this work Correspondence to: Alejandro Carlos Curino, email: acurino@criba.edu.ar Keywords: Maitake D-Fraction; mushroom; triple-negative breast cancer; antitumoral; antimetastatic Received: May 09, 2017      Accepted: April 05, 2018      Published: May 04, 2018 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.