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dc.contributor.authorFang, Wayne
dc.date.accessioned2020-06-17T15:11:15Z
dc.date.available2020-06-17T15:11:15Z
dc.date.issued2020-05
dc.identifier.urihttp://hdl.handle.net/10675.2/623403
dc.descriptionRecord is embargoed until 04/10/2025en_US
dc.description.abstractProtection of oncogenic proteins is the foundation of many hallmarks of cancer. Based on this, hsp90 inhibitors have emerged as a potentially potent strategy for cancer treatment. The clinical efficacy of the earlier Hsp90 inhibitors remains unsatisfactory, in part due to their induction of heat shock response and anti-apoptotic mechanisms in cancer cells. To identify alternative therapeutic agents without these effects, we have developed a cell-free high-throughput screen (HTS) platform based on the folding of progesterone receptor (PR) by the core components of the Hsp90 chaperoning machine. During our initial screening of 175 natural products from North African medicinal plants, we discovered the cyclic peptide AD05 as a novel Hsp90 inhibitor. AD05 has shown a powerful antitumor activity against various cancer cell lines including HeLa, Hs578T, MDA-MB231, MDA-MB453, E0771, THP1, and U937. Western blot analysis revealed that AD05 destabilizes Hsp90 client proteins without inducing heat shock response as indicated by lack of upregulation of Hsp70, Hsp40 and Hsp27. Remarkably, AD05 does not induce apoptosis but rather triggers autophagy in various cell lines.en_US
dc.language.isoen_USen_US
dc.publisherAugusta Universityen_US
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.en_US
dc.titleCharacterization of a Cyclic Peptide (ADO5) as a Novel Inhibitor of the Hsp90 Chaperoning Machineen_US
dc.typeThesisen_US
dc.contributor.departmentDepartment of Biological Sciencesen_US
dc.description.advisorAhmed Chadli
dc.description.committeeJennifer Bradford; Thomas Colbert
refterms.dateFOA2020-06-17T15:11:16Z


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