Proteasome and heat shock protein 70 (HSP70) inhibitors as therapeutic alternative in multiple myeloma
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , |
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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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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1814268285536960512 |