Crosstalk between ROS-dependent apoptotic and autophagic signaling pathways in Zn(II) phthalocyanine photodynamic therapy of melanoma

Autores
Valli, Federico; Garcia Vior, María Cecilia; Roguin, Leonor Patricia; Marino, Veronica Julieta
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Melanoma is the most aggressive type of skin cancer, highly resistant to conventional therapies. Photodynamic therapy (PDT) is a minimally invasive treatment modality that combines the use of a photosensitizer, visible light and molecular oxygen, leading to ROS generation in the specific site of irradiation. The cationic zinc(II) phthalocyanine Pc13 has shown to be a potent photosensitizer in different melanoma cell lines. In this study, we explored the intracellular signaling pathways triggered by Pc13 PDT and the role of these cascades in the phototoxic action of Pc13 in human melanoma A375 cells. ROS-dependent activation of MAPKs p38, ERK, JNK and PI3K-I/AKT was observed after treatment. Inhibition of p38 reduced Pc13 phototoxicity, whereas blockage of ERK did not affect this response. Conversely, JNK inhibition potentiated the effect of Pc13 PDT. Results obtained indicate that p38 is involved in the cleavage of PARP-1, an important mediator of apoptosis. On the other hand, Pc13 irradiation induced the activation of an autophagic program, as evidenced by enhanced levels of Beclin-1, LC3-II and GFP-LC3 punctate staining. We also demonstrated that this autophagic response is promoted by JNK and negatively regulated by PI3K-I/AKT pathway. The blockage of autophagy increased Pc13 phototoxicity and enhanced PARP-1 cleavage, revealing a protective role of this mechanism, which tends to prevent apoptotic cell death.Furthermore, reduced susceptibility to treatment and increased activation of autophagy were detected in A375 cells submitted to repeated cycles of Pc13 PDT, indicating that autophagy could represent a mechanism of resistance to PDT. The efficacy of Pc13 PDT and an improved phototoxic action in combination with chloroquine were also demonstrated in tumor spheroids. In conclusion, we showed the interplay between apoptotic and autophagic signaling pathways triggered by Pc13 PDT-induced oxidative stress. Thus, autophagy modulation represents a promising therapeutic strategy to potentiate the efficacy of PDT in melanoma.
Fil: Valli, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Garcia Vior, María Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Roguin, Leonor Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Marino, Veronica Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Materia
CELL SIGNALING
AUTOPHAGY
APOPTOSIS
PHOTODYNAMIC THERAPY
MELANOMA
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:11336/108665
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/108665
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Crosstalk between ROS-dependent apoptotic and autophagic signaling pathways in Zn(II) phthalocyanine photodynamic therapy of melanomaValli, FedericoGarcia Vior, María CeciliaRoguin, Leonor PatriciaMarino, Veronica JulietaCELL SIGNALINGAUTOPHAGYAPOPTOSISPHOTODYNAMIC THERAPYMELANOMAhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Melanoma is the most aggressive type of skin cancer, highly resistant to conventional therapies. Photodynamic therapy (PDT) is a minimally invasive treatment modality that combines the use of a photosensitizer, visible light and molecular oxygen, leading to ROS generation in the specific site of irradiation. The cationic zinc(II) phthalocyanine Pc13 has shown to be a potent photosensitizer in different melanoma cell lines. In this study, we explored the intracellular signaling pathways triggered by Pc13 PDT and the role of these cascades in the phototoxic action of Pc13 in human melanoma A375 cells. ROS-dependent activation of MAPKs p38, ERK, JNK and PI3K-I/AKT was observed after treatment. Inhibition of p38 reduced Pc13 phototoxicity, whereas blockage of ERK did not affect this response. Conversely, JNK inhibition potentiated the effect of Pc13 PDT. Results obtained indicate that p38 is involved in the cleavage of PARP-1, an important mediator of apoptosis. On the other hand, Pc13 irradiation induced the activation of an autophagic program, as evidenced by enhanced levels of Beclin-1, LC3-II and GFP-LC3 punctate staining. We also demonstrated that this autophagic response is promoted by JNK and negatively regulated by PI3K-I/AKT pathway. The blockage of autophagy increased Pc13 phototoxicity and enhanced PARP-1 cleavage, revealing a protective role of this mechanism, which tends to prevent apoptotic cell death.Furthermore, reduced susceptibility to treatment and increased activation of autophagy were detected in A375 cells submitted to repeated cycles of Pc13 PDT, indicating that autophagy could represent a mechanism of resistance to PDT. The efficacy of Pc13 PDT and an improved phototoxic action in combination with chloroquine were also demonstrated in tumor spheroids. In conclusion, we showed the interplay between apoptotic and autophagic signaling pathways triggered by Pc13 PDT-induced oxidative stress. Thus, autophagy modulation represents a promising therapeutic strategy to potentiate the efficacy of PDT in melanoma.Fil: Valli, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Garcia Vior, María Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Roguin, Leonor Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Marino, Veronica Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaElsevier Science Inc2020-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/108665Valli, Federico; Garcia Vior, María Cecilia; Roguin, Leonor Patricia; Marino, Veronica Julieta; Crosstalk between ROS-dependent apoptotic and autophagic signaling pathways in Zn(II) phthalocyanine photodynamic therapy of melanoma; Elsevier Science Inc; Free Radical Biology and Medicine; 1-1-20200891-5849CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0891584919325651info:eu-repo/semantics/altIdentifier/doi/10.1016/j.freeradbiomed.2020.01.018info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:00:51Zoai:ri.conicet.gov.ar:11336/108665instacron: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:34982025-09-03 10:00:51.826CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Crosstalk between ROS-dependent apoptotic and autophagic signaling pathways in Zn(II) phthalocyanine photodynamic therapy of melanoma
title Crosstalk between ROS-dependent apoptotic and autophagic signaling pathways in Zn(II) phthalocyanine photodynamic therapy of melanoma
spellingShingle Crosstalk between ROS-dependent apoptotic and autophagic signaling pathways in Zn(II) phthalocyanine photodynamic therapy of melanoma
Valli, Federico
CELL SIGNALING
AUTOPHAGY
APOPTOSIS
PHOTODYNAMIC THERAPY
MELANOMA
title_short Crosstalk between ROS-dependent apoptotic and autophagic signaling pathways in Zn(II) phthalocyanine photodynamic therapy of melanoma
title_full Crosstalk between ROS-dependent apoptotic and autophagic signaling pathways in Zn(II) phthalocyanine photodynamic therapy of melanoma
title_fullStr Crosstalk between ROS-dependent apoptotic and autophagic signaling pathways in Zn(II) phthalocyanine photodynamic therapy of melanoma
title_full_unstemmed Crosstalk between ROS-dependent apoptotic and autophagic signaling pathways in Zn(II) phthalocyanine photodynamic therapy of melanoma
title_sort Crosstalk between ROS-dependent apoptotic and autophagic signaling pathways in Zn(II) phthalocyanine photodynamic therapy of melanoma
dc.creator.none.fl_str_mv Valli, Federico
Garcia Vior, María Cecilia
Roguin, Leonor Patricia
Marino, Veronica Julieta
author Valli, Federico
author_facet Valli, Federico
Garcia Vior, María Cecilia
Roguin, Leonor Patricia
Marino, Veronica Julieta
author_role author
author2 Garcia Vior, María Cecilia
Roguin, Leonor Patricia
Marino, Veronica Julieta
author2_role author
author
author
dc.subject.none.fl_str_mv CELL SIGNALING
AUTOPHAGY
APOPTOSIS
PHOTODYNAMIC THERAPY
MELANOMA
topic CELL SIGNALING
AUTOPHAGY
APOPTOSIS
PHOTODYNAMIC THERAPY
MELANOMA
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Melanoma is the most aggressive type of skin cancer, highly resistant to conventional therapies. Photodynamic therapy (PDT) is a minimally invasive treatment modality that combines the use of a photosensitizer, visible light and molecular oxygen, leading to ROS generation in the specific site of irradiation. The cationic zinc(II) phthalocyanine Pc13 has shown to be a potent photosensitizer in different melanoma cell lines. In this study, we explored the intracellular signaling pathways triggered by Pc13 PDT and the role of these cascades in the phototoxic action of Pc13 in human melanoma A375 cells. ROS-dependent activation of MAPKs p38, ERK, JNK and PI3K-I/AKT was observed after treatment. Inhibition of p38 reduced Pc13 phototoxicity, whereas blockage of ERK did not affect this response. Conversely, JNK inhibition potentiated the effect of Pc13 PDT. Results obtained indicate that p38 is involved in the cleavage of PARP-1, an important mediator of apoptosis. On the other hand, Pc13 irradiation induced the activation of an autophagic program, as evidenced by enhanced levels of Beclin-1, LC3-II and GFP-LC3 punctate staining. We also demonstrated that this autophagic response is promoted by JNK and negatively regulated by PI3K-I/AKT pathway. The blockage of autophagy increased Pc13 phototoxicity and enhanced PARP-1 cleavage, revealing a protective role of this mechanism, which tends to prevent apoptotic cell death.Furthermore, reduced susceptibility to treatment and increased activation of autophagy were detected in A375 cells submitted to repeated cycles of Pc13 PDT, indicating that autophagy could represent a mechanism of resistance to PDT. The efficacy of Pc13 PDT and an improved phototoxic action in combination with chloroquine were also demonstrated in tumor spheroids. In conclusion, we showed the interplay between apoptotic and autophagic signaling pathways triggered by Pc13 PDT-induced oxidative stress. Thus, autophagy modulation represents a promising therapeutic strategy to potentiate the efficacy of PDT in melanoma.
Fil: Valli, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Garcia Vior, María Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Roguin, Leonor Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Marino, Veronica Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
description Melanoma is the most aggressive type of skin cancer, highly resistant to conventional therapies. Photodynamic therapy (PDT) is a minimally invasive treatment modality that combines the use of a photosensitizer, visible light and molecular oxygen, leading to ROS generation in the specific site of irradiation. The cationic zinc(II) phthalocyanine Pc13 has shown to be a potent photosensitizer in different melanoma cell lines. In this study, we explored the intracellular signaling pathways triggered by Pc13 PDT and the role of these cascades in the phototoxic action of Pc13 in human melanoma A375 cells. ROS-dependent activation of MAPKs p38, ERK, JNK and PI3K-I/AKT was observed after treatment. Inhibition of p38 reduced Pc13 phototoxicity, whereas blockage of ERK did not affect this response. Conversely, JNK inhibition potentiated the effect of Pc13 PDT. Results obtained indicate that p38 is involved in the cleavage of PARP-1, an important mediator of apoptosis. On the other hand, Pc13 irradiation induced the activation of an autophagic program, as evidenced by enhanced levels of Beclin-1, LC3-II and GFP-LC3 punctate staining. We also demonstrated that this autophagic response is promoted by JNK and negatively regulated by PI3K-I/AKT pathway. The blockage of autophagy increased Pc13 phototoxicity and enhanced PARP-1 cleavage, revealing a protective role of this mechanism, which tends to prevent apoptotic cell death.Furthermore, reduced susceptibility to treatment and increased activation of autophagy were detected in A375 cells submitted to repeated cycles of Pc13 PDT, indicating that autophagy could represent a mechanism of resistance to PDT. The efficacy of Pc13 PDT and an improved phototoxic action in combination with chloroquine were also demonstrated in tumor spheroids. In conclusion, we showed the interplay between apoptotic and autophagic signaling pathways triggered by Pc13 PDT-induced oxidative stress. Thus, autophagy modulation represents a promising therapeutic strategy to potentiate the efficacy of PDT in melanoma.
publishDate 2020
dc.date.none.fl_str_mv 2020-01-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/108665
Valli, Federico; Garcia Vior, María Cecilia; Roguin, Leonor Patricia; Marino, Veronica Julieta; Crosstalk between ROS-dependent apoptotic and autophagic signaling pathways in Zn(II) phthalocyanine photodynamic therapy of melanoma; Elsevier Science Inc; Free Radical Biology and Medicine; 1-1-2020
0891-5849
CONICET Digital
CONICET
url http://hdl.handle.net/11336/108665
identifier_str_mv Valli, Federico; Garcia Vior, María Cecilia; Roguin, Leonor Patricia; Marino, Veronica Julieta; Crosstalk between ROS-dependent apoptotic and autophagic signaling pathways in Zn(II) phthalocyanine photodynamic therapy of melanoma; Elsevier Science Inc; Free Radical Biology and Medicine; 1-1-2020
0891-5849
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0891584919325651
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.freeradbiomed.2020.01.018
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science Inc
publisher.none.fl_str_mv Elsevier Science Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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