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dc.contributor.authorSamadi, Abbas K.
dc.contributor.authorZhang, Xuan
dc.contributor.authorMukerji, Ridhwi
dc.contributor.authorDonnelly, Alison C.
dc.contributor.authorBlagg, Brian S. J.
dc.contributor.authorCohen, Mark S.
dc.date.accessioned2018-02-01T18:15:33Z
dc.date.available2018-02-01T18:15:33Z
dc.date.issued2011-12-22
dc.identifier.citationSamadi, A. K., Zhang, X., Mukerji, R., Donnelly, A. C., Blagg, B. S., & Cohen, M. S. (2011). A novel C-terminal HSP90 inhibitor KU135 induces apoptosis and cell cycle arrest in melanoma cells. Cancer Letters, 312(2), 158–167. http://doi.org/10.1016/j.canlet.2011.07.031en_US
dc.identifier.urihttp://hdl.handle.net/1808/25901
dc.description.abstractHeat shock protein 90 (Hsp90) is differentially expressed in tumor cells including melanoma and involved in proper folding, stabilization and regulation of cellular proteins. We investigated a novobiocin-derived Hsp90 C-terminal inhibitor, KU135, for anti-proliferative effects in melanoma cells. The results indicate that KU135 reduced cell viability and cell proliferation in melanoma cells and IC50 values for A735(DRO), M14(NPA), B16F10 and SKMEL28 cells were 0.82, 0.92, 1.33 and 1.30 M respectively. KU135 induced a more potent anti-proliferative effect in most melanoma cells versus N-terminal Hsp90 inhibitor 17AAG. KU135 induced apoptosis in melanoma cells, as indicated by annexin V/PI staining, reduction in the mitochondrial membrane potential, mitochondrial cytochrome C release and caspase 3 activation. KU135 reduced levels of Hsp90 client proteins Akt, BRAF, RAF-1, cyclin B and cdc25 proteins. Additionally, it reduced Hsp70, Hsp90 paralog, GRP94 and HSF1 levels. KU135 induced strong G2/M cell cycle arrest, associated with decreased expression of cdc25c, cyclin B and increased phosphorylation of cdc25c. These finding show that KU135 reduced cell survival, proliferation, and induces apoptosis in melanoma cells. We suggest that KU135 may be a potential candidate for cancer therapy against melanoma.en_US
dc.publisherElsevieren_US
dc.rightsThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.subjectHsp90 inhibitoren_US
dc.subjectC-terminalen_US
dc.subjectMelanomaen_US
dc.titleA novel C-terminal HSP90 inhibitor KU135 induces apoptosis and cell cycle arrest in melanoma cellsen_US
dc.typeArticleen_US
kusw.kuauthorDonnelly, Alison C.
kusw.kuauthorBlagg, Brian S.
kusw.kudepartmentMedicinal Chemistryen_US
dc.identifier.doi10.1016/j.canlet.2011.07.031en_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC5683962en_US
dc.rights.accessrightsopenAccessen_US


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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Except where otherwise noted, this item's license is described as: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.