2026-04-17T12:09:56Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/86082024-02-08T01:05:28Zcom_10259_3592com_10259_3591com_10259.4_106com_10259_2604com_10259_3924com_10259_5086col_10259_3930col_10259_3925

Small molecule anion carriers facilitate lactate transport in model liposomes and cells Alonso Carrillo, Daniel Arias Betancur, Alain Carreira Barral, Israel Fontova Pale, Pere Soto Cerrato, Vanessa García Valverde, María Pérez Tomás, Ricardo Quesada Pato, Roberto Biología molecular Química orgánica Bioquímica Molecular biology Chemistry, Organic Biochemistry 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. This research has been financially supported by Consejería de Educación de la Junta de Castilla y León (project BU067P20) and Ministerio de Ciencia e Innovación (project PID2020-117610RB-I00). D.A.-C., I.C.-B. and P.F. thank Consejería de Educación de la Junta de Castilla y León, European Regional Development Fund (ERDF) and European Social Fund (ESF) for their pre-doctoral (D.A.-C.) and post-doctoral (I.C.-B. and P.F.) contracts. A.A.-B. thanks to PFCHA/Becas Chile (Folio#72200156). The authors gratefully acknowledge Andrea Sancho-Medina for her contributions to transmembrane anion transport experiments. 2024-02-07T07:45:24Z 2024-02-07T07:45:24Z 2023-09 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 2589-0042 http://hdl.handle.net/10259/8608 10.1016/j.isci.2023.107898 eng iScience. 2023, V. 26, n. 10, 107898 https://doi.org/10.1016/j.isci.2023.107898 Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess application/pdf Elsevier