Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/70240
DC FieldValueLanguage
dc.contributor.authorChiu, Y.J.en_US
dc.contributor.authorHour, M.J.en_US
dc.contributor.authorLu, C.C.en_US
dc.contributor.authorChung, J.G.en_US
dc.contributor.authorKuo, S.C.en_US
dc.contributor.authorHuang, W.W.en_US
dc.contributor.authorChen, H.J.en_US
dc.contributor.authorJin, Y.A.en_US
dc.contributor.authorYang, J.S.en_US
dc.date2011zh_TW
dc.date.accessioned2014-06-11T05:59:33Z-
dc.date.available2014-06-11T05:59:33Z-
dc.identifier.issn0736-0266zh_TW
dc.identifier.urihttp://hdl.handle.net/11455/70240-
dc.description.abstractHuman osteogenic sarcoma is the most common primary bone tumor. Despite of the success of frontline therapy, about 40% of patients have disease progression and further therapy is palliative and toxic. In this study, we developed a novel quinazoline HMJ-30 to investigate the cell growth inhibition and apoptotic responses in U-2 OS human osteogenic sarcoma cells. Our results demonstrated that HMJ-30 significantly reduced cell viabilities of U-2 OS, HOS, and 143B cells in a dose-dependent manner, but it exhibited low cytotoxicity in normal hFOB cells. HMJ-30 induced DNA damage and apoptosis in U-2 OS cells as revealed by morphologic changes, comet assay and DAPI staining. Immuno-staining, colorimetric assays, and Western blotting analyses indicated that activities of caspase-8, caspase-9, and caspase-3 and the levels of Bcl-2 family-related proteins (Bcl-2, Mcl-1, Bax, BAD, and t-Bid) were altered in HMJ-30-treated U-2 OS cells. Pretreatment of cells with caspase-8, -9, and -3 specific inhibitors significantly reduced the cell growth inhibition. HMJ-30-induced apoptosis was mediated through both death-receptor and mitochondria-dependent apoptotic pathways in U-2 OS cells. HMJ-30 induced early phosphorylation of p53(Ser18) was through the activation of ataxia telangiectasia mutated (ATM) in U-2 OS cells. The cell growth inhibition by HMJ-30 was substantially attenuated either by the pre-incubation of U-2 OS cells with N-acetylcysteine (NAC, an antioxidant) and caffeine (an ATM kinase inhibitor) or by p53 knockdown via RNAi. In conclusion, ROS dependent-ATM/p53 signaling pathway is involved in HMJ-30-induced apoptosis in U-2 OS cells. (C) 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1448-1456, 2011en_US
dc.language.isoen_USzh_TW
dc.relationJournal of Orthopaedic Researchen_US
dc.relation.ispartofseriesJournal of Orthopaedic Research, Volume 29, Issue 9, Page(s) 1448-1456.en_US
dc.relation.urihttp://dx.doi.org/10.1002/jor.21398en_US
dc.subjectHMJ-30en_US
dc.subjecthuman osteogenic sarcoma U-2 OS cellsen_US
dc.subjectapoptosisen_US
dc.subjectATMen_US
dc.subjectp53en_US
dc.subjectmitochondria-dependent pathwaysen_US
dc.subjectcanceren_US
dc.subjectosteosarcomaen_US
dc.subjectagentsen_US
dc.subjectp53en_US
dc.subjectdnaen_US
dc.subjectatmen_US
dc.subjectautophosphorylationen_US
dc.subjectchemotherapyen_US
dc.subjectinhibitionen_US
dc.titleNovel Quinazoline HMJ-30 Induces U-2 OS Human Osteogenic Sarcoma Cell Apoptosis through Induction of Oxidative Stress and Up-Regulation of ATM/p53 Signaling Pathwayen_US
dc.typeJournal Articlezh_TW
dc.identifier.doi10.1002/jor.21398zh_TW
Appears in Collections:期刊論文
文件中的檔案:

取得全文請前往華藝線上圖書館



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.