Antitumoral and antimetastatic activity of Maitake D-Fraction in triple-negative breast cancer cells
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Eliana Noelia Alonso1,*, María Julia Ferronato1,*, María Eugenia Fermento1, Norberto Ariel Gandini1, Alejandro López Romero2, Josefina Alejandra Guevara1, María Marta Facchinetti1 and Alejandro Carlos Curino1
1Laboratorio 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
2Departamento de Hematología, IACA Laboratorios, Bahía Blanca, Argentina
*These authors contributed equally to this work
Alejandro Carlos Curino, email: [email protected]
Keywords: Maitake D-Fraction; mushroom; triple-negative breast cancer; antitumoral; antimetastatic
Received: May 09, 2017 Accepted: April 05, 2018 Published: May 04, 2018
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.
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