ATTENTION: The software behind KU ScholarWorks is being upgraded to a new version. Starting July 15th, users will not be able to log in to the system, add items, nor make any changes until the new version is in place at the end of July. Searching for articles and opening files will continue to work while the system is being updated.
If you have any questions, please contact Marianne Reed at mreed@ku.edu .
A novel C-terminal HSP90 inhibitor KU135 induces apoptosis and cell cycle arrest in melanoma cells
dc.contributor.author | Samadi, Abbas K. | |
dc.contributor.author | Zhang, Xuan | |
dc.contributor.author | Mukerji, Ridhwi | |
dc.contributor.author | Donnelly, Alison C. | |
dc.contributor.author | Blagg, Brian S. J. | |
dc.contributor.author | Cohen, Mark S. | |
dc.date.accessioned | 2018-02-01T18:15:33Z | |
dc.date.available | 2018-02-01T18:15:33Z | |
dc.date.issued | 2011-12-22 | |
dc.identifier.citation | Samadi, 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.2011.07.031 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/25901 | |
dc.description.abstract | Heat 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.publisher | Elsevier | en_US |
dc.rights | 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. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.subject | Hsp90 inhibitor | en_US |
dc.subject | C-terminal | en_US |
dc.subject | Melanoma | en_US |
dc.title | A novel C-terminal HSP90 inhibitor KU135 induces apoptosis and cell cycle arrest in melanoma cells | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Donnelly, Alison C. | |
kusw.kuauthor | Blagg, Brian S. | |
kusw.kudepartment | Medicinal Chemistry | en_US |
dc.identifier.doi | 10.1016/j.canlet.2011.07.031 | 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 | PMC5683962 | en_US |
dc.rights.accessrights | openAccess | en_US |
Files in this item
This item appears in the following Collection(s)
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.