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dc.contributor.authorGrogan, Patrick T.
dc.contributor.authorSleder, Kristina D.
dc.contributor.authorSamadi, Abbas K.
dc.contributor.authorTimmermann, Barbara N.
dc.contributor.authorCohen, Mark S.
dc.date.accessioned2017-06-13T20:39:35Z
dc.date.available2017-06-13T20:39:35Z
dc.date.issued2013-06
dc.identifier.citationGrogan, P.T., Sleder, K.D., Samadi, A.K. et al. Invest New Drugs (2013) 31: 545. doi:10.1007/s10637-012-9888-5en_US
dc.identifier.urihttp://hdl.handle.net/1808/24497
dc.description.abstractWithaferin A (WA), a steroidal lactone derived from the plant Vassobia breviflora, has been reported to have anti-proliferative, pro-apoptotic, and anti-angiogenic properties against cancer growth. In this study, we identified several key underlying mechanisms of anticancer action of WA in glioblastoma cells. WA was found to inhibit proliferation by inducing a dose-dependent G2/M cell cycle arrest and promoting cell death through both intrinsic and extrinsic apoptotic pathways. This was accompanied by an inhibitory shift in the Akt/mTOR signaling pathway which included diminished expression and/or phosphorylation of Akt, mTOR, p70 S6K, and p85 S6K with increased activation of AMPKα and the tumor suppressor tuberin/TSC2. Alterations in proteins of the MAPK pathway and cell surface receptors like EGFR, Her2/ErbB2, and c-Met were also observed. WA induced an N-acetyl-L-cysteinerepressible enhancement in cellular oxidative potential/stress with subsequent induction of a heat shock stress response primarily through HSP70, HSP32, and HSP27 upregulation and HSF1 downregulation. Taken together, we suggest that WA may represent a promising chemotherapeutic candidate in glioblastoma therapy warranting further translational evaluation.en_US
dc.publisherSpringer Verlagen_US
dc.rights© Springer Science+Business Media New York 2012en_US
dc.subjectWithaferin Aen_US
dc.subjectGlioblastoma multiformeen_US
dc.subjectOxidative stressen_US
dc.subjectHeat shock responseen_US
dc.subjectAkt/mTOR pathwayen_US
dc.subjectMAPK pathwayen_US
dc.titleCytotoxicity of withaferin A in glioblastomas involves induction of an oxidative stress-mediated heat shock response while altering Akt/mTOR and MAPK signaling pathwaysen_US
dc.typeArticleen_US
kusw.kuauthorTimmermann, Barbara N.
kusw.kudepartmentMedicinal Chemistryen_US
dc.identifier.doi10.1007/s10637-012-9888-5en_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC3677827en_US
dc.rights.accessrightsopenAccess


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