Melanoma Xenografts Growth Inhibition by Solanum Tuberosum Aspartic Proteases 3 (StAP3) Treatment

Autores
Ibañez, Irene Laura; Muñóz, Fernando; Zoppi, J.; Abaurrea, R.; Scandogliero, E.; Duran, Hebe Alicia; Guevara, Maria Gabriela
Año de publicación
2020
Idioma
español castellano
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
The swaposin domain is present in plant aspartic proteases (APs) inserted into the C-terminal domain as an extra region known as plant-specific insert (PSI). The PSI domain interacts with the plasma membrane, causing cell permeabilization, thus killing plant and human pathogens. A typical Solanum tuberosum AP (StAP) named as StAP3 was demonstrated to have cytotoxic activity against cancer cells and no effect in normal cells in vitro. The toxicity of StAP3 was assessed in a mice model, showing no signs of systemic toxicity. Malignant melanoma (MM) is one of the most aggressive cancers, with high metastatic ability and resistant to therapies. Thus, the pursuing of novel agents against MM is still challenging. Herein, we aimed to evaluate the in vivo antitumor effect of StAP3 in MM. Subcutaneous A375 human melanoma xenografts in athymic nude mice were induced. Once tumors developed (mean larger dimension = 3.8 ± 0.09 mm), mice were treated with StAP3 (6 µg/mg body weight, subcutaneously under the tumor at a single dose) or physiologic solution (controls). Animal experiments complied with the ARRIVE guidelines and were performed with protocols approved by the Argentine National Atomic Energy Commission Animal Care in accordance with the EU Directive 2010/63/EU and NIH Publications No. 8023, revised 1978. A significant inhibition of MM tumors growth was observed in StAP3-treated mice (p < 0.05) vs. controls. This was detected immediately after treatment and was sustained until 15 days post-treatment, with a maximum inhibition of 76%, when control tumors reached 200 mm3 and animals were sacrificed. As far as we know, this is the first report showing the in vivo effect of a plant AP whose action mechanism would be mediated by membrane destabilization, which may be explained by the plasma membrane composition with high levels of phosphatidylserine in the outer leaflet of cancer cells. These results suggest the potential of these plant proteases as anticancer agents.
Fil: Ibañez, Irene Laura. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes | Comision Nacional de Energia Atomica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes.; Argentina
Fil: Muñóz, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina
Fil: Zoppi, J.. Hospital Privado de la Comunidad; Argentina
Fil: Abaurrea, R.. Laboratorio de Análisis Clínicos y Bacteriológicos; Argentina
Fil: Scandogliero, E.. Laboratorio de Análisis Clínicos y Bacteriológicos; Argentina
Fil: Duran, Hebe Alicia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes | Comision Nacional de Energia Atomica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes.; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Ezeiza; Argentina. Universidad Nacional de San Martín; Argentina
Fil: Guevara, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina
LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LXVIII Reunión Anual de la Sociedad Argentina de Inmunología (SAI); Reunión Anual de la Sociedad Argentina de Fisiología (SAFIS)
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Fisiología
Materia
POTATO
CANCER
MELANOMA
PROTEASES
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:11336/216932
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Melanoma Xenografts Growth Inhibition by Solanum Tuberosum Aspartic Proteases 3 (StAP3) TreatmentIbañez, Irene LauraMuñóz, FernandoZoppi, J.Abaurrea, R.Scandogliero, E.Duran, Hebe AliciaGuevara, Maria GabrielaPOTATOCANCERMELANOMAPROTEASEShttps://purl.org/becyt/ford/3.5https://purl.org/becyt/ford/3The swaposin domain is present in plant aspartic proteases (APs) inserted into the C-terminal domain as an extra region known as plant-specific insert (PSI). The PSI domain interacts with the plasma membrane, causing cell permeabilization, thus killing plant and human pathogens. A typical Solanum tuberosum AP (StAP) named as StAP3 was demonstrated to have cytotoxic activity against cancer cells and no effect in normal cells in vitro. The toxicity of StAP3 was assessed in a mice model, showing no signs of systemic toxicity. Malignant melanoma (MM) is one of the most aggressive cancers, with high metastatic ability and resistant to therapies. Thus, the pursuing of novel agents against MM is still challenging. Herein, we aimed to evaluate the in vivo antitumor effect of StAP3 in MM. Subcutaneous A375 human melanoma xenografts in athymic nude mice were induced. Once tumors developed (mean larger dimension = 3.8 ± 0.09 mm), mice were treated with StAP3 (6 µg/mg body weight, subcutaneously under the tumor at a single dose) or physiologic solution (controls). Animal experiments complied with the ARRIVE guidelines and were performed with protocols approved by the Argentine National Atomic Energy Commission Animal Care in accordance with the EU Directive 2010/63/EU and NIH Publications No. 8023, revised 1978. A significant inhibition of MM tumors growth was observed in StAP3-treated mice (p < 0.05) vs. controls. This was detected immediately after treatment and was sustained until 15 days post-treatment, with a maximum inhibition of 76%, when control tumors reached 200 mm3 and animals were sacrificed. As far as we know, this is the first report showing the in vivo effect of a plant AP whose action mechanism would be mediated by membrane destabilization, which may be explained by the plasma membrane composition with high levels of phosphatidylserine in the outer leaflet of cancer cells. These results suggest the potential of these plant proteases as anticancer agents.Fil: Ibañez, Irene Laura. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes | Comision Nacional de Energia Atomica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes.; ArgentinaFil: Muñóz, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Zoppi, J.. Hospital Privado de la Comunidad; ArgentinaFil: Abaurrea, R.. Laboratorio de Análisis Clínicos y Bacteriológicos; ArgentinaFil: Scandogliero, E.. Laboratorio de Análisis Clínicos y Bacteriológicos; ArgentinaFil: Duran, Hebe Alicia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes | Comision Nacional de Energia Atomica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes.; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Ezeiza; Argentina. Universidad Nacional de San Martín; ArgentinaFil: Guevara, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaLXV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LXVIII Reunión Anual de la Sociedad Argentina de Inmunología (SAI); Reunión Anual de la Sociedad Argentina de Fisiología (SAFIS)ArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaSociedad Argentina de FisiologíaFundación Revista Medicina2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/216932Melanoma Xenografts Growth Inhibition by Solanum Tuberosum Aspartic Proteases 3 (StAP3) Treatment; LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LXVIII Reunión Anual de la Sociedad Argentina de Inmunología (SAI); Reunión Anual de la Sociedad Argentina de Fisiología (SAFIS); Argentina; 2020; 138-1380025-76801669-9106CONICET DigitalCONICETspainfo:eu-repo/semantics/altIdentifier/url/https://medicinabuenosaires.com/revistas/vol80-20/s5/Mv80s5.pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:31:39Zoai:ri.conicet.gov.ar:11336/216932instacron: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:34982025-10-15 15:31:40.211CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Melanoma Xenografts Growth Inhibition by Solanum Tuberosum Aspartic Proteases 3 (StAP3) Treatment
title Melanoma Xenografts Growth Inhibition by Solanum Tuberosum Aspartic Proteases 3 (StAP3) Treatment
spellingShingle Melanoma Xenografts Growth Inhibition by Solanum Tuberosum Aspartic Proteases 3 (StAP3) Treatment
Ibañez, Irene Laura
POTATO
CANCER
MELANOMA
PROTEASES
title_short Melanoma Xenografts Growth Inhibition by Solanum Tuberosum Aspartic Proteases 3 (StAP3) Treatment
title_full Melanoma Xenografts Growth Inhibition by Solanum Tuberosum Aspartic Proteases 3 (StAP3) Treatment
title_fullStr Melanoma Xenografts Growth Inhibition by Solanum Tuberosum Aspartic Proteases 3 (StAP3) Treatment
title_full_unstemmed Melanoma Xenografts Growth Inhibition by Solanum Tuberosum Aspartic Proteases 3 (StAP3) Treatment
title_sort Melanoma Xenografts Growth Inhibition by Solanum Tuberosum Aspartic Proteases 3 (StAP3) Treatment
dc.creator.none.fl_str_mv Ibañez, Irene Laura
Muñóz, Fernando
Zoppi, J.
Abaurrea, R.
Scandogliero, E.
Duran, Hebe Alicia
Guevara, Maria Gabriela
author Ibañez, Irene Laura
author_facet Ibañez, Irene Laura
Muñóz, Fernando
Zoppi, J.
Abaurrea, R.
Scandogliero, E.
Duran, Hebe Alicia
Guevara, Maria Gabriela
author_role author
author2 Muñóz, Fernando
Zoppi, J.
Abaurrea, R.
Scandogliero, E.
Duran, Hebe Alicia
Guevara, Maria Gabriela
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv POTATO
CANCER
MELANOMA
PROTEASES
topic POTATO
CANCER
MELANOMA
PROTEASES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The swaposin domain is present in plant aspartic proteases (APs) inserted into the C-terminal domain as an extra region known as plant-specific insert (PSI). The PSI domain interacts with the plasma membrane, causing cell permeabilization, thus killing plant and human pathogens. A typical Solanum tuberosum AP (StAP) named as StAP3 was demonstrated to have cytotoxic activity against cancer cells and no effect in normal cells in vitro. The toxicity of StAP3 was assessed in a mice model, showing no signs of systemic toxicity. Malignant melanoma (MM) is one of the most aggressive cancers, with high metastatic ability and resistant to therapies. Thus, the pursuing of novel agents against MM is still challenging. Herein, we aimed to evaluate the in vivo antitumor effect of StAP3 in MM. Subcutaneous A375 human melanoma xenografts in athymic nude mice were induced. Once tumors developed (mean larger dimension = 3.8 ± 0.09 mm), mice were treated with StAP3 (6 µg/mg body weight, subcutaneously under the tumor at a single dose) or physiologic solution (controls). Animal experiments complied with the ARRIVE guidelines and were performed with protocols approved by the Argentine National Atomic Energy Commission Animal Care in accordance with the EU Directive 2010/63/EU and NIH Publications No. 8023, revised 1978. A significant inhibition of MM tumors growth was observed in StAP3-treated mice (p < 0.05) vs. controls. This was detected immediately after treatment and was sustained until 15 days post-treatment, with a maximum inhibition of 76%, when control tumors reached 200 mm3 and animals were sacrificed. As far as we know, this is the first report showing the in vivo effect of a plant AP whose action mechanism would be mediated by membrane destabilization, which may be explained by the plasma membrane composition with high levels of phosphatidylserine in the outer leaflet of cancer cells. These results suggest the potential of these plant proteases as anticancer agents.
Fil: Ibañez, Irene Laura. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes | Comision Nacional de Energia Atomica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes.; Argentina
Fil: Muñóz, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina
Fil: Zoppi, J.. Hospital Privado de la Comunidad; Argentina
Fil: Abaurrea, R.. Laboratorio de Análisis Clínicos y Bacteriológicos; Argentina
Fil: Scandogliero, E.. Laboratorio de Análisis Clínicos y Bacteriológicos; Argentina
Fil: Duran, Hebe Alicia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes | Comision Nacional de Energia Atomica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes.; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Ezeiza; Argentina. Universidad Nacional de San Martín; Argentina
Fil: Guevara, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina
LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LXVIII Reunión Anual de la Sociedad Argentina de Inmunología (SAI); Reunión Anual de la Sociedad Argentina de Fisiología (SAFIS)
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Fisiología
description The swaposin domain is present in plant aspartic proteases (APs) inserted into the C-terminal domain as an extra region known as plant-specific insert (PSI). The PSI domain interacts with the plasma membrane, causing cell permeabilization, thus killing plant and human pathogens. A typical Solanum tuberosum AP (StAP) named as StAP3 was demonstrated to have cytotoxic activity against cancer cells and no effect in normal cells in vitro. The toxicity of StAP3 was assessed in a mice model, showing no signs of systemic toxicity. Malignant melanoma (MM) is one of the most aggressive cancers, with high metastatic ability and resistant to therapies. Thus, the pursuing of novel agents against MM is still challenging. Herein, we aimed to evaluate the in vivo antitumor effect of StAP3 in MM. Subcutaneous A375 human melanoma xenografts in athymic nude mice were induced. Once tumors developed (mean larger dimension = 3.8 ± 0.09 mm), mice were treated with StAP3 (6 µg/mg body weight, subcutaneously under the tumor at a single dose) or physiologic solution (controls). Animal experiments complied with the ARRIVE guidelines and were performed with protocols approved by the Argentine National Atomic Energy Commission Animal Care in accordance with the EU Directive 2010/63/EU and NIH Publications No. 8023, revised 1978. A significant inhibition of MM tumors growth was observed in StAP3-treated mice (p < 0.05) vs. controls. This was detected immediately after treatment and was sustained until 15 days post-treatment, with a maximum inhibition of 76%, when control tumors reached 200 mm3 and animals were sacrificed. As far as we know, this is the first report showing the in vivo effect of a plant AP whose action mechanism would be mediated by membrane destabilization, which may be explained by the plasma membrane composition with high levels of phosphatidylserine in the outer leaflet of cancer cells. These results suggest the potential of these plant proteases as anticancer agents.
publishDate 2020
dc.date.none.fl_str_mv 2020
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Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/216932
Melanoma Xenografts Growth Inhibition by Solanum Tuberosum Aspartic Proteases 3 (StAP3) Treatment; LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LXVIII Reunión Anual de la Sociedad Argentina de Inmunología (SAI); Reunión Anual de la Sociedad Argentina de Fisiología (SAFIS); Argentina; 2020; 138-138
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/216932
identifier_str_mv Melanoma Xenografts Growth Inhibition by Solanum Tuberosum Aspartic Proteases 3 (StAP3) Treatment; LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LXVIII Reunión Anual de la Sociedad Argentina de Inmunología (SAI); Reunión Anual de la Sociedad Argentina de Fisiología (SAFIS); Argentina; 2020; 138-138
0025-7680
1669-9106
CONICET Digital
CONICET
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language spa
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dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
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