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dc.contributor.authorJorfi, Samireh
dc.contributor.authorAnsa-Addo, Ephraim A.
dc.contributor.authorKholia, Sharad
dc.contributor.authorStratton, Dan
dc.contributor.authorValley, Shaunelle
dc.contributor.authorLange, Sigrun
dc.contributor.authorInal, Jameel
dc.date.accessioned2018-01-30T22:32:08Z
dc.date.available2018-01-30T22:32:08Z
dc.date.issued2015-08-25
dc.identifier.citationJorfi , S , Ansa-Addo , E A , Kholia , S , Stratton , D , Valley , S , Lange , S & Inal , J 2015 , ' Inhibition of microvesiculation sensitizes prostate cancer cells to chemotherapy and reduces docetaxel dose required to limit tumor growth in vivo ' , Scientific Reports , vol. 5 , 13006 . https://doi.org/10.1038/srep13006
dc.identifier.issn2045-2322
dc.identifier.otherPURE: 13068157
dc.identifier.otherPURE UUID: 067a210b-eb47-4e5a-9e03-c949d5ef9b79
dc.identifier.otherScopus: 84940063564
dc.identifier.otherPubMed: 26302712
dc.identifier.urihttp://hdl.handle.net/2299/19674
dc.descriptionThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
dc.description.abstractMicrovesicles shed from cells carry constituents of the cell cytoplasm, including, of importance in multidrug resistance to cancer chemotherapy, drugs that the tumor cell attempts to efflux. To see whether such drugs could be used at lower concentrations with the same efficacy, it was first shown that microvesiculation of prostate cancer (PCa) cells, PC3, could be inhibited pharmacologically with calpeptin (calpain inhibitor) and by siRNA (CAPNS1). In cells treated with docetaxel (DTX), this inhibition resulted in a third-fold increase in intracellular concentrations of DTX. As a result, 20-fold lower concentrations of DTX (5 nM) could be used, in the presence of calpeptin (20μM) inducing the same degree of apoptosis after 48 h in PC3 cells, as 100 nM of DTX alone. Inhibition of microvesiculation similarly improved combination chemotherapy (DTX and methotrexate). In a mouse xenograft model of PCa, DTX (0.1 mg/kg) together with calpeptin (10 mg/kg), administered i.p., significantly reduced tumor volumes compared to DTX alone (0.1 mg/kg) and brought about the same reductions in tumor growth as 10 mg/kg of DTX alone. As well as further reducing vascularization, it also increased apoptosis and reduced proliferation of PC3 cells in tumor xenografts.en
dc.format.extent13
dc.language.isoeng
dc.relation.ispartofScientific Reports
dc.rightsOpen
dc.subjectGeneral
dc.titleInhibition of microvesiculation sensitizes prostate cancer cells to chemotherapy and reduces docetaxel dose required to limit tumor growth in vivoen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionDepartment of Biological and Environmental Sciences
dc.contributor.institutionBiosciences Research Group
dc.description.statusPeer reviewed
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=84940063564&partnerID=8YFLogxK
dc.relation.schoolSchool of Life and Medical Sciences
dc.description.versiontypeFinal Published version
dcterms.dateAccepted2015-08-25
rioxxterms.versionVoR
rioxxterms.versionofrecordhttps://doi.org/10.1038/srep13006
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.rights.accesstypeOpen


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