Metformin as an adjuvant to photodynamic therapy in resistant basal cell carcinoma cells

Photodynamic Therapy (PDT) with methyl-aminolevulinate (MAL-PDT) is being used for the treatment of Basal Cell Carcinoma (BCC), although resistant cells may appear. Normal differentiated cells depend primarily on mitochondrial oxidative phosphorylation (OXPHOS) to generate energy, but cancer cells s...

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Authors: Mascaraque, Marta, Delgado-Wicke, Pablo, Nuevo-Tapioles, Cristina, Gracia-Cazaña, Tamara, Abarca-Lachen, Edgar, González, Salvador, Cuezva, José M., Gilaberte, Yolanda, Juarranz, Ángeles
Format: article
Status:Published version
Publication Date:2020
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/237610
Online Access:http://hdl.handle.net/10261/237610
Access Level:Open access
Keyword:Basal cell carcinoma
Photodynamic therapy
Resistance
Metabolic markers
Metformin
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spelling Metformin as an adjuvant to photodynamic therapy in resistant basal cell carcinoma cellsMascaraque, MartaDelgado-Wicke, PabloNuevo-Tapioles, CristinaGracia-Cazaña, TamaraAbarca-Lachen, EdgarGonzález, SalvadorCuezva, José M.Gilaberte, YolandaJuarranz, ÁngelesBasal cell carcinomaPhotodynamic therapyResistanceMetabolic markersMetforminPhotodynamic Therapy (PDT) with methyl-aminolevulinate (MAL-PDT) is being used for the treatment of Basal Cell Carcinoma (BCC), although resistant cells may appear. Normal differentiated cells depend primarily on mitochondrial oxidative phosphorylation (OXPHOS) to generate energy, but cancer cells switch this metabolism to aerobic glycolysis (Warburg effect), influencing the response to therapies. We have analyzed the expression of metabolic markers (β-F1-ATPase/GAPDH (glyceraldehyde-3-phosphate dehydrogenase) ratio, pyruvate kinase M2 (PKM2), oxygen consume ratio, and lactate extracellular production) in the resistance to PDT of mouse BCC cell lines (named ASZ and CSZ, heterozygous for ptch1). We have also evaluated the ability of metformin (Metf), an antidiabetic type II compound that acts through inhibition of the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway to sensitize resistant cells to PDT. The results obtained indicated that resistant cells showed an aerobic glycolysis metabolism. The treatment with Metf induced arrest in the G0/G1 phase and a reduction in the lactate extracellular production in all cell lines. The addition of Metf to MAL-PDT improved the cytotoxic effect on parental and resistant cells, which was not dependent on the PS protoporphyrin IX (PpIX) production. After Metf + MAL-PDT treatment, activation of pAMPK was detected, suppressing the mTOR pathway in most of the cells. Enhanced PDT-response with Metf was also observed in ASZ tumors. In conclusion, Metf increased the response to MAL-PDT in murine BCC cells resistant to PDT with aerobic glycolysis.Spanish grants from Instituto de Salud Carlos III MINECO and Feder Funds (FIS PI15/00974 and PI18/00708) and Ministerio de Ciencia, Innovación y Universidades (SAF2016-75916-R)Multidisciplinary Digital Publishing InstituteInstituto de Salud Carlos IIIMinisterio de Ciencia, Innovación y Universidades (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120202021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/237610reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.3390/cancers12030668Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2376102026-05-22T06:33:51Z
dc.title.none.fl_str_mv Metformin as an adjuvant to photodynamic therapy in resistant basal cell carcinoma cells
title Metformin as an adjuvant to photodynamic therapy in resistant basal cell carcinoma cells
spellingShingle Metformin as an adjuvant to photodynamic therapy in resistant basal cell carcinoma cells
Mascaraque, Marta
Basal cell carcinoma
Photodynamic therapy
Resistance
Metabolic markers
Metformin
title_short Metformin as an adjuvant to photodynamic therapy in resistant basal cell carcinoma cells
title_full Metformin as an adjuvant to photodynamic therapy in resistant basal cell carcinoma cells
title_fullStr Metformin as an adjuvant to photodynamic therapy in resistant basal cell carcinoma cells
title_full_unstemmed Metformin as an adjuvant to photodynamic therapy in resistant basal cell carcinoma cells
title_sort Metformin as an adjuvant to photodynamic therapy in resistant basal cell carcinoma cells
dc.creator.none.fl_str_mv Mascaraque, Marta
Delgado-Wicke, Pablo
Nuevo-Tapioles, Cristina
Gracia-Cazaña, Tamara
Abarca-Lachen, Edgar
González, Salvador
Cuezva, José M.
Gilaberte, Yolanda
Juarranz, Ángeles
author Mascaraque, Marta
author_facet Mascaraque, Marta
Delgado-Wicke, Pablo
Nuevo-Tapioles, Cristina
Gracia-Cazaña, Tamara
Abarca-Lachen, Edgar
González, Salvador
Cuezva, José M.
Gilaberte, Yolanda
Juarranz, Ángeles
author_role author
author2 Delgado-Wicke, Pablo
Nuevo-Tapioles, Cristina
Gracia-Cazaña, Tamara
Abarca-Lachen, Edgar
González, Salvador
Cuezva, José M.
Gilaberte, Yolanda
Juarranz, Ángeles
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Ministerio de Ciencia, Innovación y Universidades (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Basal cell carcinoma
Photodynamic therapy
Resistance
Metabolic markers
Metformin
topic Basal cell carcinoma
Photodynamic therapy
Resistance
Metabolic markers
Metformin
description Photodynamic Therapy (PDT) with methyl-aminolevulinate (MAL-PDT) is being used for the treatment of Basal Cell Carcinoma (BCC), although resistant cells may appear. Normal differentiated cells depend primarily on mitochondrial oxidative phosphorylation (OXPHOS) to generate energy, but cancer cells switch this metabolism to aerobic glycolysis (Warburg effect), influencing the response to therapies. We have analyzed the expression of metabolic markers (β-F1-ATPase/GAPDH (glyceraldehyde-3-phosphate dehydrogenase) ratio, pyruvate kinase M2 (PKM2), oxygen consume ratio, and lactate extracellular production) in the resistance to PDT of mouse BCC cell lines (named ASZ and CSZ, heterozygous for ptch1). We have also evaluated the ability of metformin (Metf), an antidiabetic type II compound that acts through inhibition of the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway to sensitize resistant cells to PDT. The results obtained indicated that resistant cells showed an aerobic glycolysis metabolism. The treatment with Metf induced arrest in the G0/G1 phase and a reduction in the lactate extracellular production in all cell lines. The addition of Metf to MAL-PDT improved the cytotoxic effect on parental and resistant cells, which was not dependent on the PS protoporphyrin IX (PpIX) production. After Metf + MAL-PDT treatment, activation of pAMPK was detected, suppressing the mTOR pathway in most of the cells. Enhanced PDT-response with Metf was also observed in ASZ tumors. In conclusion, Metf increased the response to MAL-PDT in murine BCC cells resistant to PDT with aerobic glycolysis.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/237610
url http://hdl.handle.net/10261/237610
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.3390/cancers12030668
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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