title: Apoptosis prediction via inhibition of AKT signaling pathway by neogrifolin.
abstract: Neogrifolin, a natural biologically active substance isolated from the edible bodies of the mushroom Albatrellus confluens, has been shown to possess several pharmacological properties. No studies were investigated against osteosarcoma cancer. Hence, in this study, we investigated the apoptosis-inducing effects and the mechanisms of neogrifolin on human osteosarcoma cells. Our results demonstrated that neogrifolin induced concentration- and time-dependent suppression of proliferation. Further, induction of apoptosis in U2OS and MG63 osteosarcoma cell lines were also observed. Neogrifolin induced the release of cytochrome c accompanied by activation of caspase-9, caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP). In addition, z-VAD-fmk, a universal inhibitor of caspases, prevented caspase-3 activation and PARP cleavage and inhibited neogrifolin-induced cell growth inhibition. Furthermore, neogrifolin treatment resulted in a reduction of phosphorylated AKT level, FOXO transcription factor, and glycogen synthase kinase 3 (GSK3). Knockdown of GSK3 with siRNA inhibited the apoptotic effects of neogrifolin. On the other hand, neogrifolin treatment also down-regulated the expression of the inhibitor of apoptosis protein (IAP) in both osteosarcoma cells. Collectively, our results suggested that neogrifolin is a potential candidate for osteosarcoma.
authors.affiliation: Department of Orthopedics, Linyi People's Hospital 27 Jiefang Road, Linyi City 276003, Shandong Province, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Linyi People's Hospital 27 Jiefang Road, Linyi City 276003, Shandong Province, P.R. China.
authors.forename: Guo-Fang
authors.initials: GF
authors.lastname: Peng
authors.affiliation: Department of Orthopedics, Linyi People's Hospital 27 Jiefang Road, Linyi City 276003, Shandong Province, P.R. China.
authors.forename: Xiang-Zhen
authors.initials: XZ
authors.lastname: Han
authors.affiliation: Department of Orthopedics, Linyi People's Hospital 27 Jiefang Road, Linyi City 276003, Shandong Province, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Linyi People's Hospital 27 Jiefang Road, Linyi City 276003, Shandong Province, P.R. China.
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Linyi People's Hospital 27 Jiefang Road, Linyi City 276003, Shandong Province, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D012516:Osteosarcoma / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012118:Resorcinols / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: C000605323:4-farnesyl-5-methylresorcinol; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D012118:Resorcinols; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
keywords: AKT signaling pathway; Neogrifolin; osteosarcoma