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dc.contributor.authorLeibou, Stav
dc.contributor.authorLu, Sumin
dc.contributor.authorDebbab, Abdssamad
dc.contributor.authorChadli, Ahmed
dc.date.accessioned2017-03-09T21:47:55Z
dc.date.available2017-03-09T21:47:55Z
dc.date.issued2017-03
dc.identifier.urihttp://hdl.handle.net/10675.2/621334
dc.descriptionPoster presented at the 18th Annual Phi Kappa Phi Student Research and Fine Arts Conferenceen
dc.description.abstractMolecular chaperones have been the focus of intense research for their important role in cancer cell homeostasis. Heat shock protein 90 (Hsp90) promotes metastasis, evasion of apoptosis, and proliferative angiogenesis in tumors through preserving the stability and functionality of its client proteins [1]. While the first generation of Hsp90 inhibitors has proven effective in hindering Hsp90 function, they have shown low clinical efficacy in part due to the induction of anti-apoptotic proteins Hsp27, Hsp40, and Hsp70 [2,3]. It is therefore our objective to develop novel efficacious Hsp90 inhibitors without these detrimental effects. During our screen for novel Hsp90 inhibitors, we found that the natural product, Chetomin, is a potent inhibitor of the Hsp90 machine chaperoning activity. Our in vitro data using human and murine mammary carcinoma cell lines suggest that Chetomin is effective in causing degradation of several known Hsp90 physiological client proteins that are crucial to cancer cell proliferation and survival. While the molecular mechanism by which Chetomin inhibits the Hsp90 function is still unclear, our data suggests that Chetomin is highly efficacious in killing cancer cells without induction of the anti-apoptotic proteins as does the first generation of Hsp90 inhibitors making Chetomin a promising new therapeutic agent.
dc.description.sponsorshipNational Institutes of Healthen
dc.language.isoenen
dc.subjectNeoplasmsen
dc.subjectHSP90 Heat-Shock Proteinsen
dc.subjectChetominen
dc.titleChetomin as a Potent Hsp90 Inhibitoren
dc.typeOtheren
dc.contributor.departmentGeorgia Cancer Centeren
refterms.dateFOA2019-04-10T08:23:33Z
html.description.abstractMolecular chaperones have been the focus of intense research for their important role in cancer cell homeostasis. Heat shock protein 90 (Hsp90) promotes metastasis, evasion of apoptosis, and proliferative angiogenesis in tumors through preserving the stability and functionality of its client proteins [1]. While the first generation of Hsp90 inhibitors has proven effective in hindering Hsp90 function, they have shown low clinical efficacy in part due to the induction of anti-apoptotic proteins Hsp27, Hsp40, and Hsp70 [2,3]. It is therefore our objective to develop novel efficacious Hsp90 inhibitors without these detrimental effects. During our screen for novel Hsp90 inhibitors, we found that the natural product, Chetomin, is a potent inhibitor of the Hsp90 machine chaperoning activity. Our in vitro data using human and murine mammary carcinoma cell lines suggest that Chetomin is effective in causing degradation of several known Hsp90 physiological client proteins that are crucial to cancer cell proliferation and survival. While the molecular mechanism by which Chetomin inhibits the Hsp90 function is still unclear, our data suggests that Chetomin is highly efficacious in killing cancer cells without induction of the anti-apoptotic proteins as does the first generation of Hsp90 inhibitors making Chetomin a promising new therapeutic agent.


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