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dc.contributor.authorVishal, Chaturvedi
dc.contributor.authorKumar, Jonnala Ujwal
dc.contributor.authorVeera Brahmendra Swamy, Cherukuvada
dc.contributor.authorNandini, Rangaraj
dc.contributor.authorSrinivas, Gunda
dc.contributor.authorKumaresan, Rathinam
dc.contributor.authorShashi, Singh
dc.contributor.authorSreedhar, Amere Subbarao
dc.date.accessioned2014-08-27T09:49:25Z
dc.date.available2014-08-27T09:49:25Z
dc.date.issued2011-06-07
dc.identifier.citationA S Sreedhar, Chaturvedi Vishal, Jonnala Ujwal Kumar, Cherukuvada Veera Brahmendra Swamy, Rangaraj Nandini, et al. (2011) Repercussion of Mitochondria Deformity Induced by Anti-Hsp90 Drug 17AAG in Human Tumor Cells. DTI: 11. doi:10.4137/DTI.S6582.
dc.identifier.pmid22087060
dc.identifier.doi10.4137/DTI.S6582
dc.identifier.urihttp://hdl.handle.net/10754/325367
dc.description.abstractInhibiting Hsp90 chaperone roles using 17AAG induces cytostasis or apoptosis in tumor cells through destabilization of several mutated cancer promoting proteins. Although mitochondria are central in deciding the fate of cells, 17AAG induced effects on tumor cell mitochondria were largely unknown. Here, we show that Hsp90 inhibition with 17AAG first affects mitochondrial integrity in different human tumor cells, neuroblastoma, cervical cancer and glial cells. Using human neuroblastoma tumor cells, we found the early effects associated with a change in mitochondrial membrane potential, elongation and engorgement of mitochondria because of an increased matrix vacuolization. These effects are specific to Hsp90 inhibition as other chemotherapeutic drugs did not induce similar mitochondrial deformity. Further, the effects are independent of oxidative damage and cytoarchitecture destabilization since cytoskeletal disruptors and mitochondrial metabolic inhibitors also do not induce similar deformity induced by 17AAG. The 1D PAGE LC MS/ MS mitochondrial proteome analysis of 17AAG treated human neuroblastoma cells showed a loss of 61% proteins from membrane, metabolic, chaperone and ribonucleoprotein families. About 31 unmapped protein IDs were identified from proteolytic processing map using Swiss-Prot accession number, and converted to the matching gene name searching the ExPASy proteomics server. Our studies display that Hsp90 inhibition effects at first embark on mitochondria of tumor cells and compromise mitochondrial integrity. the author(s), publisher and licensee Libertas Academica Ltd.
dc.language.isoen
dc.publisherAboutscience Srl
dc.rights© the author(s), publisher and licensee Libertas Academica Ltd.
dc.rightsThis is an open access article. Unrestricted non-commercial use is permitted provided the original work is properly cited.
dc.rightsArchived with thanks to Drug Target Insights
dc.subject??m
dc.subject17AAG
dc.subjectHsp90
dc.subjectMitochondria
dc.subjectTumor cells
dc.subjectcisplatin
dc.subjectcurcumin
dc.subjectcytochalasin D
dc.subjectcytochrome c
dc.subjectdigitonin
dc.subjectheat shock protein 90
dc.subjecthydrogen peroxide
dc.subjectnovobiocin
dc.subjectpaclitaxel
dc.subjectradicicol
dc.subjectreactive oxygen metabolite
dc.subjecttanespimycin
dc.subjectvincristine
dc.subjectcell vacuole
dc.subjectcontrolled study
dc.subjectglioblastoma
dc.subjecthuman cell
dc.subjectliquid chromatography
dc.subjectliver mitochondrion
dc.subjectmass spectrometry
dc.subjectmitochondrial deformity
dc.subjectmitochondrial elongation
dc.subjectmitochondrial membrane potential
dc.subjectmitochondrion
dc.subjectmitochondrion swelling
dc.subjectneuroblastoma cell
dc.subjectpolyacrylamide gel electrophoresis
dc.subjectproteomics
dc.subjecttumor cell
dc.subjectuterine cervix cancer
dc.titleRepercussion of mitochondria deformity induced by anti-Hsp90 drug 17AAG in human tumor cells
dc.typeArticle
dc.contributor.departmentBioscience Core Lab
dc.identifier.journalDrug Target Insights
dc.identifier.pmcidPMC3178438
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionCentre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)
kaust.personGunda Srinivas,
refterms.dateFOA2018-06-14T04:28:01Z
dc.date.published-online2011-06-07
dc.date.published-print2011-01


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