Repercussion of mitochondria deformity induced by anti-Hsp90 drug 17AAG in human tumor cells

Handle URI:
http://hdl.handle.net/10754/325367
Title:
Repercussion of mitochondria deformity induced by anti-Hsp90 drug 17AAG in human tumor cells
Authors:
Vishal, Chaturvedi; Kumar, Jonnala Ujwal; Veera Brahmendra Swamy, Cherukuvada; Nandini, Rangaraj; Srinivas, Gunda; Kumaresan, Rathinam; Shashi, Singh; Sreedhar, Amere Subbarao
Abstract:
Inhibiting 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.
KAUST Department:
Biosciences Core Lab
Citation:
A 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.
Publisher:
Libertas Academica
Journal:
Drug Target Insights
Issue Date:
7-Jun-2011
DOI:
10.4137/DTI.S6582
PubMed ID:
22087060
PubMed Central ID:
PMC3178438
Type:
Article
Appears in Collections:
Articles; Biosciences Core Lab

Full metadata record

DC FieldValue Language
dc.contributor.authorVishal, Chaturvedien
dc.contributor.authorKumar, Jonnala Ujwalen
dc.contributor.authorVeera Brahmendra Swamy, Cherukuvadaen
dc.contributor.authorNandini, Rangarajen
dc.contributor.authorSrinivas, Gundaen
dc.contributor.authorKumaresan, Rathinamen
dc.contributor.authorShashi, Singhen
dc.contributor.authorSreedhar, Amere Subbaraoen
dc.date.accessioned2014-08-27T09:49:25Z-
dc.date.available2014-08-27T09:49:25Z-
dc.date.issued2011-06-07en
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.en
dc.identifier.pmid22087060en
dc.identifier.doi10.4137/DTI.S6582en
dc.identifier.urihttp://hdl.handle.net/10754/325367en
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.en
dc.language.isoenen
dc.publisherLibertas Academicaen
dc.rights© the author(s), publisher and licensee Libertas Academica Ltd.en
dc.rightsThis is an open access article. Unrestricted non-commercial use is permitted provided the original work is properly cited.en
dc.rightsArchived with thanks to Drug Target Insightsen
dc.subject??men
dc.subject17AAGen
dc.subjectHsp90en
dc.subjectMitochondriaen
dc.subjectTumor cellsen
dc.subjectcisplatinen
dc.subjectcurcuminen
dc.subjectcytochalasin Den
dc.subjectcytochrome cen
dc.subjectdigitoninen
dc.subjectheat shock protein 90en
dc.subjecthydrogen peroxideen
dc.subjectnovobiocinen
dc.subjectpaclitaxelen
dc.subjectradicicolen
dc.subjectreactive oxygen metaboliteen
dc.subjecttanespimycinen
dc.subjectvincristineen
dc.subjectcell vacuoleen
dc.subjectcontrolled studyen
dc.subjectglioblastomaen
dc.subjecthuman cellen
dc.subjectliquid chromatographyen
dc.subjectliver mitochondrionen
dc.subjectmass spectrometryen
dc.subjectmitochondrial deformityen
dc.subjectmitochondrial elongationen
dc.subjectmitochondrial membrane potentialen
dc.subjectmitochondrionen
dc.subjectmitochondrion swellingen
dc.subjectneuroblastoma cellen
dc.subjectpolyacrylamide gel electrophoresisen
dc.subjectproteomicsen
dc.subjecttumor cellen
dc.subjectuterine cervix canceren
dc.titleRepercussion of mitochondria deformity induced by anti-Hsp90 drug 17AAG in human tumor cellsen
dc.typeArticleen
dc.contributor.departmentBiosciences Core Laben
dc.identifier.journalDrug Target Insightsen
dc.identifier.pmcidPMC3178438en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionCentre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, Indiaen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
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