Inhibiting cancer metabolism by aromatic carbohydrate amphiphiles that act as antagonists of the glucose transporter GLUT1

Detalhes bibliográficos
Autor(a) principal: Brito, Alexandra
Data de Publicação: 2020
Outros Autores: Pereira, Patrícia M., Costa, Diana Soares da, Reis, R. L., Ulijn, Rein V., Lewis, Rein V., Pires, R. A., Pashkuleva, I.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/66345
Resumo: We report on aromatic N-glucosides that inhibit selectively the cancer metabolism via two coexistent mechanisms: by initial deprivation of the glucose uptake through competitive binding in the glucose binding pocket of GLUT1 and by formation of a sequestering nanoscale supramolecular network at the cell surface through localized (biocatalytic) self-assembly. We demonstrate that the expression of the cancer associated GLUT1 and alkaline phosphatase are crucial for the effectiveness of this combined approach: cancer cells that overexpress both proteins are prompter to cell death when compared to GLUT1 overexpressing cells. Overall, we showcase that the synergism between physical and biochemical deprivation of cancer metabolism is a powerful approach for development of effective anticancer therapies.
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spelling Inhibiting cancer metabolism by aromatic carbohydrate amphiphiles that act as antagonists of the glucose transporter GLUT1ApoptosisBiocatalytic self-assemblyGLUT inhibitorOsteosarcomaWarburg effectScience & TechnologyWe report on aromatic N-glucosides that inhibit selectively the cancer metabolism via two coexistent mechanisms: by initial deprivation of the glucose uptake through competitive binding in the glucose binding pocket of GLUT1 and by formation of a sequestering nanoscale supramolecular network at the cell surface through localized (biocatalytic) self-assembly. We demonstrate that the expression of the cancer associated GLUT1 and alkaline phosphatase are crucial for the effectiveness of this combined approach: cancer cells that overexpress both proteins are prompter to cell death when compared to GLUT1 overexpressing cells. Overall, we showcase that the synergism between physical and biochemical deprivation of cancer metabolism is a powerful approach for development of effective anticancer therapies.We acknowledge the EU's H2020 program (Forecast 668983; THE DISCOVERIES CTR 739572) and the Portuguese FCT (BD/ 113794/2015; BPD/85790/2012; PTDC/NAN-MAT/28468/2017 CANCER_CAGE) for the financial support. The authors gratefully acknowledge members of the MSKCC Small Animal Imaging Core Facility, the Radiochemistry and Molecular Imaging Probe Core (both supported by NIH P30 CA008748) as well as NIH R35 CA232130 (JSL). PMRP acknowledges the Tow Foundation Postdoctoral Fellowship from the MSK Center for Molecular Imaging and Nanotechnology. AB is grateful to the Portuguese League Against Cancer for her Fellowship. RVU acknowledges support from the US Army Research 719 Office (proposal number 69180-CH). We thank Luca Gasperini for his help in the quantification of NBDG fluorescence images using the Cell Profiler software and Andreia Carvalho for providing comments and suggestions that were helpful in acquiring data for this manuscript.Royal Society of ChemistryUniversidade do MinhoBrito, AlexandraPereira, Patrícia M.Costa, Diana Soares daReis, R. L.Ulijn, Rein V.Lewis, Rein V.Pires, R. A.Pashkuleva, I.20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/66345engBrito A., Pereira P. M. R., Soares da Costa D., Reis R. L., Ulijn R. V., Lewis J. S., Pires R. A., Pashkuleva I. Inhibiting cancer metabolism by aromatic carbohydrate amphiphiles that act as antagonists of the glucose transporter GLUT1, Chemical Science, Vol. 11, Issue 14, pp. 3737-3744, doi:10.1039/D0SC00954G, 20202041-653910.1039/D0SC00954Ghttps://doi.org/10.1039/D0SC00954Ginfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-05-11T06:03:50Zoai:repositorium.sdum.uminho.pt:1822/66345Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-05-11T06:03:50Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Inhibiting cancer metabolism by aromatic carbohydrate amphiphiles that act as antagonists of the glucose transporter GLUT1
title Inhibiting cancer metabolism by aromatic carbohydrate amphiphiles that act as antagonists of the glucose transporter GLUT1
spellingShingle Inhibiting cancer metabolism by aromatic carbohydrate amphiphiles that act as antagonists of the glucose transporter GLUT1
Brito, Alexandra
Apoptosis
Biocatalytic self-assembly
GLUT inhibitor
Osteosarcoma
Warburg effect
Science & Technology
title_short Inhibiting cancer metabolism by aromatic carbohydrate amphiphiles that act as antagonists of the glucose transporter GLUT1
title_full Inhibiting cancer metabolism by aromatic carbohydrate amphiphiles that act as antagonists of the glucose transporter GLUT1
title_fullStr Inhibiting cancer metabolism by aromatic carbohydrate amphiphiles that act as antagonists of the glucose transporter GLUT1
title_full_unstemmed Inhibiting cancer metabolism by aromatic carbohydrate amphiphiles that act as antagonists of the glucose transporter GLUT1
title_sort Inhibiting cancer metabolism by aromatic carbohydrate amphiphiles that act as antagonists of the glucose transporter GLUT1
author Brito, Alexandra
author_facet Brito, Alexandra
Pereira, Patrícia M.
Costa, Diana Soares da
Reis, R. L.
Ulijn, Rein V.
Lewis, Rein V.
Pires, R. A.
Pashkuleva, I.
author_role author
author2 Pereira, Patrícia M.
Costa, Diana Soares da
Reis, R. L.
Ulijn, Rein V.
Lewis, Rein V.
Pires, R. A.
Pashkuleva, I.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Brito, Alexandra
Pereira, Patrícia M.
Costa, Diana Soares da
Reis, R. L.
Ulijn, Rein V.
Lewis, Rein V.
Pires, R. A.
Pashkuleva, I.
dc.subject.por.fl_str_mv Apoptosis
Biocatalytic self-assembly
GLUT inhibitor
Osteosarcoma
Warburg effect
Science & Technology
topic Apoptosis
Biocatalytic self-assembly
GLUT inhibitor
Osteosarcoma
Warburg effect
Science & Technology
description We report on aromatic N-glucosides that inhibit selectively the cancer metabolism via two coexistent mechanisms: by initial deprivation of the glucose uptake through competitive binding in the glucose binding pocket of GLUT1 and by formation of a sequestering nanoscale supramolecular network at the cell surface through localized (biocatalytic) self-assembly. We demonstrate that the expression of the cancer associated GLUT1 and alkaline phosphatase are crucial for the effectiveness of this combined approach: cancer cells that overexpress both proteins are prompter to cell death when compared to GLUT1 overexpressing cells. Overall, we showcase that the synergism between physical and biochemical deprivation of cancer metabolism is a powerful approach for development of effective anticancer therapies.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/66345
url http://hdl.handle.net/1822/66345
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Brito A., Pereira P. M. R., Soares da Costa D., Reis R. L., Ulijn R. V., Lewis J. S., Pires R. A., Pashkuleva I. Inhibiting cancer metabolism by aromatic carbohydrate amphiphiles that act as antagonists of the glucose transporter GLUT1, Chemical Science, Vol. 11, Issue 14, pp. 3737-3744, doi:10.1039/D0SC00954G, 2020
2041-6539
10.1039/D0SC00954G
https://doi.org/10.1039/D0SC00954G
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Royal Society of Chemistry
publisher.none.fl_str_mv Royal Society of Chemistry
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv mluisa.alvim@gmail.com
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