Fomes fomentarius, an edible mushroom, is known to have anti-cancer, anti-inflammatory, and anti-diabetes effects. However, the underlying anti-cancer mechanism of F. fomentarius is unknown. To determine the molecular mechanism of the anti-cancer effects of F. fomentarius, various methods were used including fluorescence-activated cell sorting, Western blotting, migration, and crystal violet assays. F. fomentarius ethanol extract (FFE) decreased cell viability in six cancer cell lines (MDA-MB-231, MCF-7, A549, H460, DU145, and PC-3). FFE decreased the migration of MDA-MB-231 cells without causing cell toxicity. Furthermore, FFE attenuated the expression of matrix metalloproteinase-9 and phosphorylation of Akt as well as increased E-cadherin in MDA-MB-231 cells. FFE arrested the S and G2/M populations by inhibiting the expression of cell cycle regulatory proteins such as cyclin-dependent kinase 2, cyclin A/E, and S-phase kinase-associated protein 2. FFE increased the sub-G1 population and expression of cleaved caspase-9, -3, and cleaved poly adenosine diphosphate (ADP-ribose) polymerase at 72 h and suppressed B-cell lymphoma 2. Interestingly, FFE and AKT inhibitors showed similar effects in MDA-MB-231 cells. Additionally, FFE contained betulin which inhibited p-AKT in MDA-MB-231 cells. Our findings demonstrate that FFE inhibits cell motility and growth and induces apoptosis by inhibiting the phsphoinositide 3- kinase /AKT pathway and caspase activation.
Keywords: AKT inhibitor; Fomes fomentarius; PI3/AKT; apoptosis; migration.