Cargando…
Small molecule anion carriers facilitate lactate transport in model liposomes and cells
An excessive production of lactate by cancer cells fosters tumor growth and metastasis. Therefore, targeting lactate metabolism and transport offers a new therapeutic strategy against cancer, based on dependency of some cancer cells for lactate as energy fuel or as oncogenic signal. Herein we presen...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10543179/ https://www.ncbi.nlm.nih.gov/pubmed/37790273 http://dx.doi.org/10.1016/j.isci.2023.107898 |
_version_ | 1785114242853109760 |
---|---|
author | Alonso-Carrillo, Daniel Arias-Betancur, Alain Carreira-Barral, Israel Fontova, Pere Soto-Cerrato, Vanessa García-Valverde, María Pérez-Tomás, Ricardo Quesada, Roberto |
author_facet | Alonso-Carrillo, Daniel Arias-Betancur, Alain Carreira-Barral, Israel Fontova, Pere Soto-Cerrato, Vanessa García-Valverde, María Pérez-Tomás, Ricardo Quesada, Roberto |
author_sort | Alonso-Carrillo, Daniel |
collection | PubMed |
description | An excessive production of lactate by cancer cells fosters tumor growth and metastasis. Therefore, targeting lactate metabolism and transport offers a new therapeutic strategy against cancer, based on dependency of some cancer cells for lactate as energy fuel or as oncogenic signal. Herein we present a family of anionophores based on the structure of click-tambjamines that have proved to be extremely active lactate carriers across phospholipid membranes. Compound 1, the most potent lactate transmembrane carrier, was studied in HeLa cells. The use of a monocarboxylate transporters (MCTs) inhibitor proved that 1 is an active lactate transporter in living cells, confirming the results obtained in phospholipid vesicles. Moreover, an additive effect of compound 1 with cisplatin was observed in HeLa cells. Identification of active lactate anionophores working in living cells opens up ways to exploit this class of compounds as molecular tools and drugs addressing dysregulated lactate metabolism. |
format | Online Article Text |
id | pubmed-10543179 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-105431792023-10-03 Small molecule anion carriers facilitate lactate transport in model liposomes and cells Alonso-Carrillo, Daniel Arias-Betancur, Alain Carreira-Barral, Israel Fontova, Pere Soto-Cerrato, Vanessa García-Valverde, María Pérez-Tomás, Ricardo Quesada, Roberto iScience Article An excessive production of lactate by cancer cells fosters tumor growth and metastasis. Therefore, targeting lactate metabolism and transport offers a new therapeutic strategy against cancer, based on dependency of some cancer cells for lactate as energy fuel or as oncogenic signal. Herein we present a family of anionophores based on the structure of click-tambjamines that have proved to be extremely active lactate carriers across phospholipid membranes. Compound 1, the most potent lactate transmembrane carrier, was studied in HeLa cells. The use of a monocarboxylate transporters (MCTs) inhibitor proved that 1 is an active lactate transporter in living cells, confirming the results obtained in phospholipid vesicles. Moreover, an additive effect of compound 1 with cisplatin was observed in HeLa cells. Identification of active lactate anionophores working in living cells opens up ways to exploit this class of compounds as molecular tools and drugs addressing dysregulated lactate metabolism. Elsevier 2023-09-14 /pmc/articles/PMC10543179/ /pubmed/37790273 http://dx.doi.org/10.1016/j.isci.2023.107898 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Alonso-Carrillo, Daniel Arias-Betancur, Alain Carreira-Barral, Israel Fontova, Pere Soto-Cerrato, Vanessa García-Valverde, María Pérez-Tomás, Ricardo Quesada, Roberto Small molecule anion carriers facilitate lactate transport in model liposomes and cells |
title | Small molecule anion carriers facilitate lactate transport in model liposomes and cells |
title_full | Small molecule anion carriers facilitate lactate transport in model liposomes and cells |
title_fullStr | Small molecule anion carriers facilitate lactate transport in model liposomes and cells |
title_full_unstemmed | Small molecule anion carriers facilitate lactate transport in model liposomes and cells |
title_short | Small molecule anion carriers facilitate lactate transport in model liposomes and cells |
title_sort | small molecule anion carriers facilitate lactate transport in model liposomes and cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10543179/ https://www.ncbi.nlm.nih.gov/pubmed/37790273 http://dx.doi.org/10.1016/j.isci.2023.107898 |
work_keys_str_mv | AT alonsocarrillodaniel smallmoleculeanioncarriersfacilitatelactatetransportinmodelliposomesandcells AT ariasbetancuralain smallmoleculeanioncarriersfacilitatelactatetransportinmodelliposomesandcells AT carreirabarralisrael smallmoleculeanioncarriersfacilitatelactatetransportinmodelliposomesandcells AT fontovapere smallmoleculeanioncarriersfacilitatelactatetransportinmodelliposomesandcells AT sotocerratovanessa smallmoleculeanioncarriersfacilitatelactatetransportinmodelliposomesandcells AT garciavalverdemaria smallmoleculeanioncarriersfacilitatelactatetransportinmodelliposomesandcells AT pereztomasricardo smallmoleculeanioncarriersfacilitatelactatetransportinmodelliposomesandcells AT quesadaroberto smallmoleculeanioncarriersfacilitatelactatetransportinmodelliposomesandcells |