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

Detalhes bibliográficos
Autor(a) principal: Pereira Eugenio, Angela Isabel [UNIFESP]
Data de Publicação: 2017
Outros Autores: Fook-Alves, Veruska Lia [UNIFESP], de Oliveira, Mariana Bleker [UNIFESP], Fernando, Rodrigo Carlini [UNIFESP], Zanatta, Daniela B., Strauss, Bryan Eric, Regis Silva, Maria Regina [UNIFESP], Porcionatto, Marimelia Aparecida [UNIFESP], Braga Colleoni, Gisele Wally [UNIFESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: http://dx.doi.org/10.18632/oncotarget.22815
https://repositorio.unifesp.br/handle/11600/53980
Resumo: HSP70 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.
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spelling Proteasome and heat shock protein 70 (HSP70) inhibitors as therapeutic alternative in multiple myelomamultiple myelomaHSP70ubiquitin-proteasome systemunfolded protein responseautophagyHSP70 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.Univ Fed Sao Paulo, UNIFESP, Dept Clin & Expt Oncol, Discipline Hematol & Hemotherapy, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med, Canc Inst State Sao Paulo, Ctr Translat Invest Oncol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, UNIFESP, Dept Pathol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, UNIFESP, Dept Biochem, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, UNIFESP, Dept Clin & Expt Oncol, Discipline Hematol & Hemotherapy, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, UNIFESP, Dept Pathol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, UNIFESP, Dept Biochem, Sao Paulo, SP, BrazilWeb of ScienceConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), BrazilFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Brazil [2010/17668-6]FAPESP [2010/17668-6]Impact Journals Llc2020-07-02T18:52:15Z2020-07-02T18:52:15Z2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion114698-114709application/pdfhttp://dx.doi.org/10.18632/oncotarget.22815Oncotarget. Orchard Park, v. 8, n. 70, p. 114698-114709, 2017.10.18632/oncotarget.22815WOS000419571000030.pdf1949-2553https://repositorio.unifesp.br/handle/11600/53980WOS:000419571000030engOncotargetOrchard Parkinfo:eu-repo/semantics/openAccessPereira Eugenio, Angela Isabel [UNIFESP]Fook-Alves, Veruska Lia [UNIFESP]de Oliveira, Mariana Bleker [UNIFESP]Fernando, Rodrigo Carlini [UNIFESP]Zanatta, Daniela B.Strauss, Bryan EricRegis Silva, Maria Regina [UNIFESP]Porcionatto, Marimelia Aparecida [UNIFESP]Braga Colleoni, Gisele Wally [UNIFESP]reponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-03T05:20:50Zoai:repositorio.unifesp.br/:11600/53980Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-03T05:20:50Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Proteasome and heat shock protein 70 (HSP70) inhibitors as therapeutic alternative in multiple myeloma
title Proteasome and heat shock protein 70 (HSP70) inhibitors as therapeutic alternative in multiple myeloma
spellingShingle Proteasome and heat shock protein 70 (HSP70) inhibitors as therapeutic alternative in multiple myeloma
Pereira Eugenio, Angela Isabel [UNIFESP]
multiple myeloma
HSP70
ubiquitin-proteasome system
unfolded protein response
autophagy
title_short Proteasome and heat shock protein 70 (HSP70) inhibitors as therapeutic alternative in multiple myeloma
title_full Proteasome and heat shock protein 70 (HSP70) inhibitors as therapeutic alternative in multiple myeloma
title_fullStr Proteasome and heat shock protein 70 (HSP70) inhibitors as therapeutic alternative in multiple myeloma
title_full_unstemmed Proteasome and heat shock protein 70 (HSP70) inhibitors as therapeutic alternative in multiple myeloma
title_sort Proteasome and heat shock protein 70 (HSP70) inhibitors as therapeutic alternative in multiple myeloma
author Pereira Eugenio, Angela Isabel [UNIFESP]
author_facet Pereira Eugenio, Angela Isabel [UNIFESP]
Fook-Alves, Veruska Lia [UNIFESP]
de Oliveira, Mariana Bleker [UNIFESP]
Fernando, Rodrigo Carlini [UNIFESP]
Zanatta, Daniela B.
Strauss, Bryan Eric
Regis Silva, Maria Regina [UNIFESP]
Porcionatto, Marimelia Aparecida [UNIFESP]
Braga Colleoni, Gisele Wally [UNIFESP]
author_role author
author2 Fook-Alves, Veruska Lia [UNIFESP]
de Oliveira, Mariana Bleker [UNIFESP]
Fernando, Rodrigo Carlini [UNIFESP]
Zanatta, Daniela B.
Strauss, Bryan Eric
Regis Silva, Maria Regina [UNIFESP]
Porcionatto, Marimelia Aparecida [UNIFESP]
Braga Colleoni, Gisele Wally [UNIFESP]
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Pereira Eugenio, Angela Isabel [UNIFESP]
Fook-Alves, Veruska Lia [UNIFESP]
de Oliveira, Mariana Bleker [UNIFESP]
Fernando, Rodrigo Carlini [UNIFESP]
Zanatta, Daniela B.
Strauss, Bryan Eric
Regis Silva, Maria Regina [UNIFESP]
Porcionatto, Marimelia Aparecida [UNIFESP]
Braga Colleoni, Gisele Wally [UNIFESP]
dc.subject.por.fl_str_mv multiple myeloma
HSP70
ubiquitin-proteasome system
unfolded protein response
autophagy
topic multiple myeloma
HSP70
ubiquitin-proteasome system
unfolded protein response
autophagy
description HSP70 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.
publishDate 2017
dc.date.none.fl_str_mv 2017
2020-07-02T18:52:15Z
2020-07-02T18:52:15Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.18632/oncotarget.22815
Oncotarget. Orchard Park, v. 8, n. 70, p. 114698-114709, 2017.
10.18632/oncotarget.22815
WOS000419571000030.pdf
1949-2553
https://repositorio.unifesp.br/handle/11600/53980
WOS:000419571000030
url http://dx.doi.org/10.18632/oncotarget.22815
https://repositorio.unifesp.br/handle/11600/53980
identifier_str_mv Oncotarget. Orchard Park, v. 8, n. 70, p. 114698-114709, 2017.
10.18632/oncotarget.22815
WOS000419571000030.pdf
1949-2553
WOS:000419571000030
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Oncotarget
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 114698-114709
application/pdf
dc.coverage.none.fl_str_mv Orchard Park
dc.publisher.none.fl_str_mv Impact Journals Llc
publisher.none.fl_str_mv Impact Journals Llc
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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