title: 5,7-Dihydroxy-4'-methoxyisoflavone induces apoptosis by inhibiting the ERK and Akt pathways in human osteosarcoma cells.
abstract: Phytoestrogens are known to prevent tumor progression by inhibiting proliferation and inducing apoptosis in cancer cells. In this study we determine the effect of 5,7-dihydroxy-4'-methoxyisoflavone, a phytoestrogen, on proliferation and apoptosis in the human osteosarcoma (OS) cell line U2OS. 5,7-Dihydroxy-4'-methoxyisoflavone dose-dependently inhibited proliferation in U2OS cells, which was accompanied by an increase of early apoptotic cells. However, 5,7-dihydroxy-4'-methoxyisoflavone had little effect on the growth and apoptosis of normal human skin fibroblast (HSF) cells. This may indicate that 5,7-dihydroxy-4'-methoxyisoflavone can selectively inhibit the proliferation of cancerous cells. Meanwhile, 5,7-dihydroxy-4'-methoxyisoflavone decreased the protein levels of phosphorylated ERK and Akt. Inactivation of these pathways was confirmed by upregulation of Bax expression and downregulation of Bcl-2 expression. Phosphorylated Akt protein levels were decreased in HSF cells only at a high concentration (80 μM) of 5,7-dihydroxy-4'-methoxyisoflavone. Together, we suggest that 5,7-dihydroxy-4'-methoxyisoflavone promotes cell death of human OS cells U2OS by induction of apoptosis, which is associated with the inhibition of ERK and Akt signaling. Thus, 5,7-dihydroxy-4'-methoxyisoflavone may have less toxicity compared to normal tissue and could be a potential therapy for OS.
authors.affiliation: Renmin Hospital of Baise , Baise , China and.
authors.forename: Xiaosheng
authors.initials: X
authors.lastname: Lu
authors.forename: Jinmin
authors.initials: J
authors.lastname: Zhao
authors.forename: Tingyang
authors.initials: T
authors.lastname: Li
authors.forename: Meijing
authors.initials: M
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Liang
authors.forename: Wen
authors.initials: W
authors.lastname: Wei
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D012516:Osteosarcoma / Q000201:enzymology* / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D012867:Skin / Q000166:cytology; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D007529:Isoflavones; D047428:Protein Kinase Inhibitors; D051028:bcl-2-Associated X Protein; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: 5,7-dihydroxy-4′-methoxyisoflavone; MAPK; PI3K/Akt; apoptosis; osteosarcoma; phytoestrogen