The iron effect on the cell survival of breast cancer depends on its overload level

Autores
Gómez, Florencia Magalí; Mascaró, Marilina; Curino, Alejandro Carlos; Facchinetti, Maria Marta; Giorgi, Gisela
Año de publicación
2024
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Cancer cells develop metabolic alterations to sustain an increased proliferation. The iron is an essential element required for many bi- ological processes and its metabolism is disrupted in breast cancer (BC) cells. It has been reported that high cellular iron concentra- tion accelerates the proliferation of BC cells. However, recent works described that the iron overload induce cell death by ferroptosis, a form of cell death caused by iron-catalyzed excessive peroxidation of polyunsaturated fatty acids; being a promising therapeutic target for therapy-resistant cancers. In this study we aimed to analyze the behavior of BC cells exposed to an increasing iron overload. To that end, the murine BC cell line, LM3, was treated with increasing ferric ammonium citrate (FAC) concentrations (0- 400 μM) for 48 h and cell viability (by crystal violet), intracellular iron (by Prussian Blue), reac- tive oxygen species (ROS) (by DFCA), lipid peroxidation (TBARS) (by MDA accumulation) and the expression of divalent metal trans- porter 1 (DMT1) by immunocytochemistry, were analyzed. LM3 cell viability increased after FAC treatment with 25 μM and 50 μM (p< 0.05) but decreased with 200 μM and 400 μM FAC (p< 0.05 and p< 0.01, respectively), respect to vehicle. The ROS levels increased after FAC treatment with 50 μM (p< 0.05), 200 μM (p< 0.001) and 400 μM (p< 0.001) compared to vehicle. In addition, we detected an increase in lipid peroxidation in LM3 cells treated with 200 μM and 400 μM of FAC compared to vehicle (p< 0.01, in both). Also, we found iron accumulation as hemosiderin form and high DMT1 importer expression in LM3 cells treated with 200 μM and 400 μM of FAC, compared to vehicle. Altogether these results suggest that the effect of iron on cell viability depends on its overload level and that a high iron overload promotes the iron entry through DMT1 and its accumulation as hemosiderin inducing lower cell viability through lipid peroxidation-dependent mechanisms.
Fil: Gómez, Florencia Magalí. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Mascaró, Marilina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Giorgi, Gisela. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Biología
Asociación Argentina de Farmacología Experimental
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Materia
IRON
BREST CANCER
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/236165

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spelling The iron effect on the cell survival of breast cancer depends on its overload levelGómez, Florencia MagalíMascaró, MarilinaCurino, Alejandro CarlosFacchinetti, Maria MartaGiorgi, GiselaIRONBREST CANCERhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Cancer cells develop metabolic alterations to sustain an increased proliferation. The iron is an essential element required for many bi- ological processes and its metabolism is disrupted in breast cancer (BC) cells. It has been reported that high cellular iron concentra- tion accelerates the proliferation of BC cells. However, recent works described that the iron overload induce cell death by ferroptosis, a form of cell death caused by iron-catalyzed excessive peroxidation of polyunsaturated fatty acids; being a promising therapeutic target for therapy-resistant cancers. In this study we aimed to analyze the behavior of BC cells exposed to an increasing iron overload. To that end, the murine BC cell line, LM3, was treated with increasing ferric ammonium citrate (FAC) concentrations (0- 400 μM) for 48 h and cell viability (by crystal violet), intracellular iron (by Prussian Blue), reac- tive oxygen species (ROS) (by DFCA), lipid peroxidation (TBARS) (by MDA accumulation) and the expression of divalent metal trans- porter 1 (DMT1) by immunocytochemistry, were analyzed. LM3 cell viability increased after FAC treatment with 25 μM and 50 μM (p< 0.05) but decreased with 200 μM and 400 μM FAC (p< 0.05 and p< 0.01, respectively), respect to vehicle. The ROS levels increased after FAC treatment with 50 μM (p< 0.05), 200 μM (p< 0.001) and 400 μM (p< 0.001) compared to vehicle. In addition, we detected an increase in lipid peroxidation in LM3 cells treated with 200 μM and 400 μM of FAC compared to vehicle (p< 0.01, in both). Also, we found iron accumulation as hemosiderin form and high DMT1 importer expression in LM3 cells treated with 200 μM and 400 μM of FAC, compared to vehicle. Altogether these results suggest that the effect of iron on cell viability depends on its overload level and that a high iron overload promotes the iron entry through DMT1 and its accumulation as hemosiderin inducing lower cell viability through lipid peroxidation-dependent mechanisms.Fil: Gómez, Florencia Magalí. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Mascaró, Marilina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Giorgi, Gisela. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaLXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de LaboratorioMar del PlataArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de BiologíaAsociación Argentina de Farmacología ExperimentalAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioFundación Revista Medicina2024info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/236165The iron effect on the cell survival of breast cancer depends on its overload level; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2023; 1-40025-76801667-5746CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicinaInternacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:18:22Zoai:ri.conicet.gov.ar:11336/236165instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:18:22.828CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The iron effect on the cell survival of breast cancer depends on its overload level
title The iron effect on the cell survival of breast cancer depends on its overload level
spellingShingle The iron effect on the cell survival of breast cancer depends on its overload level
Gómez, Florencia Magalí
IRON
BREST CANCER
title_short The iron effect on the cell survival of breast cancer depends on its overload level
title_full The iron effect on the cell survival of breast cancer depends on its overload level
title_fullStr The iron effect on the cell survival of breast cancer depends on its overload level
title_full_unstemmed The iron effect on the cell survival of breast cancer depends on its overload level
title_sort The iron effect on the cell survival of breast cancer depends on its overload level
dc.creator.none.fl_str_mv Gómez, Florencia Magalí
Mascaró, Marilina
Curino, Alejandro Carlos
Facchinetti, Maria Marta
Giorgi, Gisela
author Gómez, Florencia Magalí
author_facet Gómez, Florencia Magalí
Mascaró, Marilina
Curino, Alejandro Carlos
Facchinetti, Maria Marta
Giorgi, Gisela
author_role author
author2 Mascaró, Marilina
Curino, Alejandro Carlos
Facchinetti, Maria Marta
Giorgi, Gisela
author2_role author
author
author
author
dc.subject.none.fl_str_mv IRON
BREST CANCER
topic IRON
BREST CANCER
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Cancer cells develop metabolic alterations to sustain an increased proliferation. The iron is an essential element required for many bi- ological processes and its metabolism is disrupted in breast cancer (BC) cells. It has been reported that high cellular iron concentra- tion accelerates the proliferation of BC cells. However, recent works described that the iron overload induce cell death by ferroptosis, a form of cell death caused by iron-catalyzed excessive peroxidation of polyunsaturated fatty acids; being a promising therapeutic target for therapy-resistant cancers. In this study we aimed to analyze the behavior of BC cells exposed to an increasing iron overload. To that end, the murine BC cell line, LM3, was treated with increasing ferric ammonium citrate (FAC) concentrations (0- 400 μM) for 48 h and cell viability (by crystal violet), intracellular iron (by Prussian Blue), reac- tive oxygen species (ROS) (by DFCA), lipid peroxidation (TBARS) (by MDA accumulation) and the expression of divalent metal trans- porter 1 (DMT1) by immunocytochemistry, were analyzed. LM3 cell viability increased after FAC treatment with 25 μM and 50 μM (p< 0.05) but decreased with 200 μM and 400 μM FAC (p< 0.05 and p< 0.01, respectively), respect to vehicle. The ROS levels increased after FAC treatment with 50 μM (p< 0.05), 200 μM (p< 0.001) and 400 μM (p< 0.001) compared to vehicle. In addition, we detected an increase in lipid peroxidation in LM3 cells treated with 200 μM and 400 μM of FAC compared to vehicle (p< 0.01, in both). Also, we found iron accumulation as hemosiderin form and high DMT1 importer expression in LM3 cells treated with 200 μM and 400 μM of FAC, compared to vehicle. Altogether these results suggest that the effect of iron on cell viability depends on its overload level and that a high iron overload promotes the iron entry through DMT1 and its accumulation as hemosiderin inducing lower cell viability through lipid peroxidation-dependent mechanisms.
Fil: Gómez, Florencia Magalí. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Mascaró, Marilina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Giorgi, Gisela. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Biología
Asociación Argentina de Farmacología Experimental
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
description Cancer cells develop metabolic alterations to sustain an increased proliferation. The iron is an essential element required for many bi- ological processes and its metabolism is disrupted in breast cancer (BC) cells. It has been reported that high cellular iron concentra- tion accelerates the proliferation of BC cells. However, recent works described that the iron overload induce cell death by ferroptosis, a form of cell death caused by iron-catalyzed excessive peroxidation of polyunsaturated fatty acids; being a promising therapeutic target for therapy-resistant cancers. In this study we aimed to analyze the behavior of BC cells exposed to an increasing iron overload. To that end, the murine BC cell line, LM3, was treated with increasing ferric ammonium citrate (FAC) concentrations (0- 400 μM) for 48 h and cell viability (by crystal violet), intracellular iron (by Prussian Blue), reac- tive oxygen species (ROS) (by DFCA), lipid peroxidation (TBARS) (by MDA accumulation) and the expression of divalent metal trans- porter 1 (DMT1) by immunocytochemistry, were analyzed. LM3 cell viability increased after FAC treatment with 25 μM and 50 μM (p< 0.05) but decreased with 200 μM and 400 μM FAC (p< 0.05 and p< 0.01, respectively), respect to vehicle. The ROS levels increased after FAC treatment with 50 μM (p< 0.05), 200 μM (p< 0.001) and 400 μM (p< 0.001) compared to vehicle. In addition, we detected an increase in lipid peroxidation in LM3 cells treated with 200 μM and 400 μM of FAC compared to vehicle (p< 0.01, in both). Also, we found iron accumulation as hemosiderin form and high DMT1 importer expression in LM3 cells treated with 200 μM and 400 μM of FAC, compared to vehicle. Altogether these results suggest that the effect of iron on cell viability depends on its overload level and that a high iron overload promotes the iron entry through DMT1 and its accumulation as hemosiderin inducing lower cell viability through lipid peroxidation-dependent mechanisms.
publishDate 2024
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The iron effect on the cell survival of breast cancer depends on its overload level; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2023; 1-4
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identifier_str_mv The iron effect on the cell survival of breast cancer depends on its overload level; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2023; 1-4
0025-7680
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CONICET Digital
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