Proteasome and heat shock protein 70 (HSP70) inhibitors as therapeutic alternative in multiple myeloma

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dc.citation.issue70
dc.citation.volume8
dc.contributor.authorPereira Eugenio, Angela Isabel [UNIFESP]
dc.contributor.authorFook-Alves, Veruska Lia [UNIFESP]
dc.contributor.authorde Oliveira, Mariana Bleker [UNIFESP]
dc.contributor.authorFernando, Rodrigo Carlini [UNIFESP]
dc.contributor.authorZanatta, Daniela B.
dc.contributor.authorStrauss, Bryan Eric
dc.contributor.authorRegis Silva, Maria Regina [UNIFESP]
dc.contributor.authorPorcionatto, Marimelia Aparecida [UNIFESP]
dc.contributor.authorBraga Colleoni, Gisele Wally [UNIFESP]
dc.coverageOrchard Park
dc.date.accessioned2020-07-02T18:52:15Z
dc.date.available2020-07-02T18:52:15Z
dc.date.issued2017
dc.description.abstractHSP70 connects multiple signaling pathways that work synergistically to protect tumor cells from death by proteotoxic stress and represents a possible target to establish a new approach for multiple myeloma treatment. Therefore, bioluminescent cell lines RPMI8226-LUC-PURO and U266-LUC-PURO were treated with HSP70 (VER155008) and/or proteasome (bortezomib) inhibitors and immunodeficient mice were used for subcutaneous xenograft models to evaluate tumor growth reduction and tumor growth inhibition after treatment. Bioluminescence imaging was used to follow tumor response. Treatment with bortezomib showed similar to 60% of late apoptosis in RPMI8226-LUC-PURO (without additional benefit of VER155008 in this cell line). However, U266-LUC-PURO showed similar to 60% of cell death after treatment with VER155008 (alone or with bortezomib). RPMI8226-LUC-PURO xenograft presented tumor reduction by bioluminescence imaging after treatment with bortezomib, VER155008 or drug combination compared to controls. Treatment with bortezomib, alone or combined with VER155008, showed inhibition of tumor growth assessed by bioluminescence imaging after one week in both RPMI8226-LUC-PURO and U266-LUC-PURO cell lines when compared to controls. In conclusion, our study shows that the combination of proteasome and HSP70 inhibitors induced cell death in tumor cells in vitro (late apoptosis induction) and in vivo (inhibition of tumor growth) with special benefit in U266-LUC-PURO, bearing 17p deletion.en
dc.description.affiliationUniv Fed Sao Paulo, UNIFESP, Dept Clin & Expt Oncol, Discipline Hematol & Hemotherapy, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Sao Paulo, Fac Med, Canc Inst State Sao Paulo, Ctr Translat Invest Oncol, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, UNIFESP, Dept Pathol, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, UNIFESP, Dept Biochem, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, UNIFESP, Dept Clin & Expt Oncol, Discipline Hematol & Hemotherapy, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, UNIFESP, Dept Pathol, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, UNIFESP, Dept Biochem, Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Brazil [2010/17668-6]
dc.description.sponsorshipIDFAPESP [2010/17668-6]
dc.format.extent114698-114709
dc.identifierhttp://dx.doi.org/10.18632/oncotarget.22815
dc.identifier.citationOncotarget. Orchard Park, v. 8, n. 70, p. 114698-114709, 2017.
dc.identifier.doi10.18632/oncotarget.22815
dc.identifier.fileWOS000419571000030.pdf
dc.identifier.issn1949-2553
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/53980
dc.identifier.wosWOS:000419571000030
dc.language.isoeng
dc.publisherImpact Journals Llc
dc.relation.ispartofOncotarget
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectmultiple myelomaen
dc.subjectHSP70en
dc.subjectubiquitin-proteasome systemen
dc.subjectunfolded protein responseen
dc.subjectautophagyen
dc.titleProteasome and heat shock protein 70 (HSP70) inhibitors as therapeutic alternative in multiple myelomaen
dc.typeinfo:eu-repo/semantics/article
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