ANTITUMORAL EFFECTS OF GRIFOLA FRONDOSA (MAITAKE) D FRACTION IN BREAST CANCER

CURINO, A.C.; FERRONATO, M.J.; GANDINI, N.A.; OBIOL, D. J.; FERMENTO, M.E.; FACCHINETTI, M.M.; LÓPEZ ROMERO, A.; ALONSO, E.N.

San Carlos de Bariloche

Congreso; Sistam 2015; 2015

CONICET

DFraction is a proteoglycan extract obtained from the medicinal mushroom Grifola frondosa (Maitake). Theantitumoral effect of D Fraction is mainly attributed to its immunomodulatorycapacity and numerous studies have investigated the cellular and molecularmechanisms involved in this capacity. Recently, some reports have described adirect effect of D fraction on some neoplastic cells. We propose to demonstratethat D Fraction is also able to act directly on mammary tumor cells MDA-MB-231and LM3, modulating their tumoral capacities and to elucidate the molecularmechanisms involved. We observed that D Fraction treatment decrease cellviability of MDA-MB-231 and LM3 in a dose‐ and time‐dependent manner,compared to vehicle-treated cells (WST-1 and subsequent manual counting; p<0.05). An increase in subG0/G1 cell population onboth lines (flow cytometry; p <0.01) following D fraction treatment suggeststhe induction of cell death. Furthermore, treatment of MDA-MB-231 and LM3 cellswith D Fraction decreases migratory capacity of both lines (wound healingassay; p <0.001) and invasive capacity of MDA-MB-231 (matrigel assay; p <0.001).In concordance with these results, we observed a decrease in the number ofstress fibers (immunofluorescence; p <0.001) and increased levels ofE-cadherin (western blot) in MDA-MB-231 cells following D Fraction treatment.Moreover, in a murine model of syngeneic transplantation with LM3, we demonstratedthat D Fraction treatment decreased tumor volume (D Fraction median=1.90 vscontrol median=3.46; p <0.05) and the number of lung metastases (DFraction median=0 vs control median=2; p <0.05), compared to the controlgroup. Finally, we detected that the tumor of mice treated with D Fraction showedincreased expression of the apoptotic protein Bax (immunohistochemistry; p<0.05). In conclusion, in cultureand in vivo results suggest that D Fractionaffects tumor growth and metastasis by inhibiting cell viability, migration andinvasion.