Ing: This analysis was funded by COLCIENCIAS grant number (111571250689) and Universidad Santiago de Cali grant number (DGI912621116C9). Acknowledgments: Authors thank L.M. Yepes for technical assistance. Conflicts of Interest: The authors declare no conflict of interest.AbbreviationsPKB RAC PH PI2P PI3P TcAKTlike OD Protein kinase B Related to A and Ckinases Pleckstrin homology domain Phosphatidylinositol bisphosphate Phosphatidylinositol trisphosphate AKTlike protein of Trypanosoma cruzi Optical densityInt. J. Mol. Sci. 2018, 19,12 of
JNJ-54861911 site International Journal ofMolecular SciencesArticleFomes fomentarius Ethanol Extract Exerts Inhibition of Cell Development and Motility Induction of Apoptosis through Targeting AKT in Human Breast Cancer MDAMB231 CellsSeonOK Lee 1, , MinHo Lee two, , KyungRan Lee 1 , EunOk Lee 1 and HyoJeong Lee 1, Division of Science in Korean Medicine, Graduate College, Kyung Hee University, Hoegidong, Dongdaemungu, Seoul 130701, Korea; [email protected] (S.O.L.); [email protected] (K.R.L.); [email protected] (E.O.L.) Department of meals technologies and solutions, Eulji University, Yangjidong, Sujeonggu, Seongnamsi, Gyeonggido 461713, Korea; [email protected] Correspondence: [email protected]; Tel.: 8229619625 These authors contributed equally to this work.Received: 28 December 2018; Accepted: 28 February 2019; Published: 6 MarchAbstract: Fomes fomentarius, an edible mushroom, is recognized to possess anticancer, antiinflammatory, and antidiabetes effects. Nonetheless, the underlying anticancer mechanism of F. fomentarius is unknown. To figure out the molecular mechanism from the anticancer effects of F. fomentarius, different procedures were employed such as fluorescenceactivated cell sorting, Western blotting, migration, and crystal violet assays. F. fomentarius ethanol extract (FFE) Unoprostone Membrane Transporter/Ion Channel decreased cell viability in six cancer cell lines (MDAMB231, MCF7, A549, H460, DU145, and PC3). FFE decreased the migration of MDAMB231 cells without having causing cell toxicity. Additionally, FFE attenuated the expression of matrix metalloproteinase9 and phosphorylation of Akt at the same time as elevated Ecadherin in MDAMB231 cells. FFE arrested the S and G2M populations by inhibiting the expression of cell cycle regulatory proteins including cyclindependent kinase 2, cyclin AE, and Sphase kinaseassociated protein 2. FFE improved the subG1 population and expression of cleaved caspase9, three, and cleaved poly adenosine diphosphate (ADPribose) polymerase at 72 h and suppressed Bcell lymphoma 2. Interestingly, FFE and AKT inhibitors showed similar effects in MDAMB231 cells. In addition, FFE contained betulin which inhibited pAKT in MDAMB231 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. Key phrases: Fomes fomentarius; AKT inhibitor; apoptosis; PI3AKT; migration1. Introduction Breast cancer is amongst the most typical forms of cancer in females. One particular in eight girls is diagnosed with breast cancer and approximately 12.5 will develop invasive breast cancer [1]. Triplenegative breast cancer which is associated with invasive breast cancer is usually a hugely aggressive subtype related with poor prognosis; this type accounts for 20 of breast cancer cases [2]. Triplenegative breast cancer is diagnosed depending on the absence of the three most common kinds of receptors: Estrogen, progesterone, and human epidermal growth aspect receptor two (HER2)neu genes. As a result of the lack of these rec.