dc.contributor.author | Grogan, Patrick T. | |
dc.contributor.author | Sleder, Kristina D. | |
dc.contributor.author | Samadi, Abbas K. | |
dc.contributor.author | Timmermann, Barbara N. | |
dc.contributor.author | Cohen, Mark S. | |
dc.date.accessioned | 2017-06-13T20:39:35Z | |
dc.date.available | 2017-06-13T20:39:35Z | |
dc.date.issued | 2013-06 | |
dc.identifier.citation | Grogan, P.T., Sleder, K.D., Samadi, A.K. et al. Invest New Drugs (2013) 31: 545. doi:10.1007/s10637-012-9888-5 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/24497 | |
dc.description.abstract | Withaferin 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.publisher | Springer Verlag | en_US |
dc.rights | © Springer Science+Business Media New York 2012 | en_US |
dc.subject | Withaferin A | en_US |
dc.subject | Glioblastoma multiforme | en_US |
dc.subject | Oxidative stress | en_US |
dc.subject | Heat shock response | en_US |
dc.subject | Akt/mTOR pathway | en_US |
dc.subject | MAPK pathway | en_US |
dc.title | Cytotoxicity of withaferin A in glioblastomas involves induction of an oxidative stress-mediated heat shock response while altering Akt/mTOR and MAPK signaling pathways | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Timmermann, Barbara N. | |
kusw.kudepartment | Medicinal Chemistry | en_US |
dc.identifier.doi | 10.1007/s10637-012-9888-5 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC3677827 | en_US |
dc.rights.accessrights | openAccess | |