Caffeic acid phenylethyl ester and MG132, two novel nonconventional chemotherapeutic agents, induce apoptosis of human leukemic cells by disrupting mitochondrial function

Autores
Cavaliere, Victoria; Papademetrio, Daniela Laura; Lombardo, Tomás; Costantino, Susana Nora; Blanco, Guillermo Armando C.; Alvarez Carbonetto, Elida M. del C.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The ability to modulate balance between cell survival and death is recognized for its great therapeutic potential. Therefore, research continues to focus on elucidation of cell machinery and signaling pathways that control cell proliferation and apoptosis. Conventional chemotherapeutic agents often have a cytostatic effect over tumor cells. New natural or synthetic chemotherapeutic agents have a wider spectrum of interesting antitumor activities that merit in-depth studies. In the present work, we aimed at characterizing the molecular mechanism leading to induction of cell death upon treatment of the lymphoblastoid cell line PL104 with caffeic acid phenylethyl ester (CAPE), MG132 and two conventional chemotherapeutic agents, doxorubicine (DOX) and vincristine (VCR). Our results showed several apoptotic hallmarks such as phosphatidylserine (PS) exposure on the outer leaflet of the cell membrane, nuclear fragmentation, and increase sub-G1 DNA content after all treatments. In addition, all four drugs downregulated survivin expression. CAPE and both chemotherapeutic agents reduced Bcl-2, while only CAPE and MG132 significantly increased Bax level. CAPE and VCR treatment induced the collapse of mitochondrial membrane potential (∆ψm). All compounds induced cytochrome c release from mitochondrial compartment to cytosol. However, only MG132 caused the translocation of Smac/DIABLO. Except for VCR treatment, all other drugs increased reactive oxygen species (ROS) production level. All treatments induced activation of caspases 3/7, but only CAPE and MG132 led to the activation of caspase 9. In conclusion, our results indicate that CAPE and MG132 treatment of PL104 cells induced apoptosis through the mitochondrial intrinsic pathway, whereas the apoptotic mechanism induced by DOX and VCR may proceed through the extrinsic pathway.
Fil: Cavaliere, Victoria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina
Fil: Papademetrio, Daniela Laura. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina
Fil: Lombardo, Tomás. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina
Fil: Costantino, Susana Nora. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina
Fil: Blanco, Guillermo Armando C.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina
Fil: Alvarez Carbonetto, Elida M. del C.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina
Materia
Cape
Mg132
Mitochondria
Leukemia
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:11336/8048
Acceder
id CONICETDig_8a33446d480fced05baa8c1cbfdefaac
oai_identifier_str oai:ri.conicet.gov.ar:11336/8048
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Caffeic acid phenylethyl ester and MG132, two novel nonconventional chemotherapeutic agents, induce apoptosis of human leukemic cells by disrupting mitochondrial functionCavaliere, VictoriaPapademetrio, Daniela LauraLombardo, TomásCostantino, Susana NoraBlanco, Guillermo Armando C.Alvarez Carbonetto, Elida M. del C.CapeMg132MitochondriaLeukemiahttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3The ability to modulate balance between cell survival and death is recognized for its great therapeutic potential. Therefore, research continues to focus on elucidation of cell machinery and signaling pathways that control cell proliferation and apoptosis. Conventional chemotherapeutic agents often have a cytostatic effect over tumor cells. New natural or synthetic chemotherapeutic agents have a wider spectrum of interesting antitumor activities that merit in-depth studies. In the present work, we aimed at characterizing the molecular mechanism leading to induction of cell death upon treatment of the lymphoblastoid cell line PL104 with caffeic acid phenylethyl ester (CAPE), MG132 and two conventional chemotherapeutic agents, doxorubicine (DOX) and vincristine (VCR). Our results showed several apoptotic hallmarks such as phosphatidylserine (PS) exposure on the outer leaflet of the cell membrane, nuclear fragmentation, and increase sub-G1 DNA content after all treatments. In addition, all four drugs downregulated survivin expression. CAPE and both chemotherapeutic agents reduced Bcl-2, while only CAPE and MG132 significantly increased Bax level. CAPE and VCR treatment induced the collapse of mitochondrial membrane potential (∆ψm). All compounds induced cytochrome c release from mitochondrial compartment to cytosol. However, only MG132 caused the translocation of Smac/DIABLO. Except for VCR treatment, all other drugs increased reactive oxygen species (ROS) production level. All treatments induced activation of caspases 3/7, but only CAPE and MG132 led to the activation of caspase 9. In conclusion, our results indicate that CAPE and MG132 treatment of PL104 cells induced apoptosis through the mitochondrial intrinsic pathway, whereas the apoptotic mechanism induced by DOX and VCR may proceed through the extrinsic pathway.Fil: Cavaliere, Victoria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; ArgentinaFil: Papademetrio, Daniela Laura. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; ArgentinaFil: Lombardo, Tomás. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; ArgentinaFil: Costantino, Susana Nora. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; ArgentinaFil: Blanco, Guillermo Armando C.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; ArgentinaFil: Alvarez Carbonetto, Elida M. del C.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; ArgentinaSpringer2014-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/8048Cavaliere, Victoria; Papademetrio, Daniela Laura; Lombardo, Tomás; Costantino, Susana Nora; Blanco, Guillermo Armando C.; et al.; Caffeic acid phenylethyl ester and MG132, two novel nonconventional chemotherapeutic agents, induce apoptosis of human leukemic cells by disrupting mitochondrial function; Springer; Targeted Oncology; 9; 1; 3-2014; 25-421776-2596enginfo:eu-repo/semantics/altIdentifier/url/http://link.springer.com/article/10.1007%2Fs11523-013-0256-yinfo:eu-repo/semantics/altIdentifier/doi/10.1007/s11523-013-0256-yinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:12:56Zoai:ri.conicet.gov.ar:11336/8048instacron: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:34982025-09-29 10:12:56.849CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Caffeic acid phenylethyl ester and MG132, two novel nonconventional chemotherapeutic agents, induce apoptosis of human leukemic cells by disrupting mitochondrial function
title Caffeic acid phenylethyl ester and MG132, two novel nonconventional chemotherapeutic agents, induce apoptosis of human leukemic cells by disrupting mitochondrial function
spellingShingle Caffeic acid phenylethyl ester and MG132, two novel nonconventional chemotherapeutic agents, induce apoptosis of human leukemic cells by disrupting mitochondrial function
Cavaliere, Victoria
Cape
Mg132
Mitochondria
Leukemia
title_short Caffeic acid phenylethyl ester and MG132, two novel nonconventional chemotherapeutic agents, induce apoptosis of human leukemic cells by disrupting mitochondrial function
title_full Caffeic acid phenylethyl ester and MG132, two novel nonconventional chemotherapeutic agents, induce apoptosis of human leukemic cells by disrupting mitochondrial function
title_fullStr Caffeic acid phenylethyl ester and MG132, two novel nonconventional chemotherapeutic agents, induce apoptosis of human leukemic cells by disrupting mitochondrial function
title_full_unstemmed Caffeic acid phenylethyl ester and MG132, two novel nonconventional chemotherapeutic agents, induce apoptosis of human leukemic cells by disrupting mitochondrial function
title_sort Caffeic acid phenylethyl ester and MG132, two novel nonconventional chemotherapeutic agents, induce apoptosis of human leukemic cells by disrupting mitochondrial function
dc.creator.none.fl_str_mv Cavaliere, Victoria
Papademetrio, Daniela Laura
Lombardo, Tomás
Costantino, Susana Nora
Blanco, Guillermo Armando C.
Alvarez Carbonetto, Elida M. del C.
author Cavaliere, Victoria
author_facet Cavaliere, Victoria
Papademetrio, Daniela Laura
Lombardo, Tomás
Costantino, Susana Nora
Blanco, Guillermo Armando C.
Alvarez Carbonetto, Elida M. del C.
author_role author
author2 Papademetrio, Daniela Laura
Lombardo, Tomás
Costantino, Susana Nora
Blanco, Guillermo Armando C.
Alvarez Carbonetto, Elida M. del C.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Cape
Mg132
Mitochondria
Leukemia
topic Cape
Mg132
Mitochondria
Leukemia
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The ability to modulate balance between cell survival and death is recognized for its great therapeutic potential. Therefore, research continues to focus on elucidation of cell machinery and signaling pathways that control cell proliferation and apoptosis. Conventional chemotherapeutic agents often have a cytostatic effect over tumor cells. New natural or synthetic chemotherapeutic agents have a wider spectrum of interesting antitumor activities that merit in-depth studies. In the present work, we aimed at characterizing the molecular mechanism leading to induction of cell death upon treatment of the lymphoblastoid cell line PL104 with caffeic acid phenylethyl ester (CAPE), MG132 and two conventional chemotherapeutic agents, doxorubicine (DOX) and vincristine (VCR). Our results showed several apoptotic hallmarks such as phosphatidylserine (PS) exposure on the outer leaflet of the cell membrane, nuclear fragmentation, and increase sub-G1 DNA content after all treatments. In addition, all four drugs downregulated survivin expression. CAPE and both chemotherapeutic agents reduced Bcl-2, while only CAPE and MG132 significantly increased Bax level. CAPE and VCR treatment induced the collapse of mitochondrial membrane potential (∆ψm). All compounds induced cytochrome c release from mitochondrial compartment to cytosol. However, only MG132 caused the translocation of Smac/DIABLO. Except for VCR treatment, all other drugs increased reactive oxygen species (ROS) production level. All treatments induced activation of caspases 3/7, but only CAPE and MG132 led to the activation of caspase 9. In conclusion, our results indicate that CAPE and MG132 treatment of PL104 cells induced apoptosis through the mitochondrial intrinsic pathway, whereas the apoptotic mechanism induced by DOX and VCR may proceed through the extrinsic pathway.
Fil: Cavaliere, Victoria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina
Fil: Papademetrio, Daniela Laura. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina
Fil: Lombardo, Tomás. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina
Fil: Costantino, Susana Nora. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina
Fil: Blanco, Guillermo Armando C.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina
Fil: Alvarez Carbonetto, Elida M. del C.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina
description The ability to modulate balance between cell survival and death is recognized for its great therapeutic potential. Therefore, research continues to focus on elucidation of cell machinery and signaling pathways that control cell proliferation and apoptosis. Conventional chemotherapeutic agents often have a cytostatic effect over tumor cells. New natural or synthetic chemotherapeutic agents have a wider spectrum of interesting antitumor activities that merit in-depth studies. In the present work, we aimed at characterizing the molecular mechanism leading to induction of cell death upon treatment of the lymphoblastoid cell line PL104 with caffeic acid phenylethyl ester (CAPE), MG132 and two conventional chemotherapeutic agents, doxorubicine (DOX) and vincristine (VCR). Our results showed several apoptotic hallmarks such as phosphatidylserine (PS) exposure on the outer leaflet of the cell membrane, nuclear fragmentation, and increase sub-G1 DNA content after all treatments. In addition, all four drugs downregulated survivin expression. CAPE and both chemotherapeutic agents reduced Bcl-2, while only CAPE and MG132 significantly increased Bax level. CAPE and VCR treatment induced the collapse of mitochondrial membrane potential (∆ψm). All compounds induced cytochrome c release from mitochondrial compartment to cytosol. However, only MG132 caused the translocation of Smac/DIABLO. Except for VCR treatment, all other drugs increased reactive oxygen species (ROS) production level. All treatments induced activation of caspases 3/7, but only CAPE and MG132 led to the activation of caspase 9. In conclusion, our results indicate that CAPE and MG132 treatment of PL104 cells induced apoptosis through the mitochondrial intrinsic pathway, whereas the apoptotic mechanism induced by DOX and VCR may proceed through the extrinsic pathway.
publishDate 2014
dc.date.none.fl_str_mv 2014-03
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/11336/8048
Cavaliere, Victoria; Papademetrio, Daniela Laura; Lombardo, Tomás; Costantino, Susana Nora; Blanco, Guillermo Armando C.; et al.; Caffeic acid phenylethyl ester and MG132, two novel nonconventional chemotherapeutic agents, induce apoptosis of human leukemic cells by disrupting mitochondrial function; Springer; Targeted Oncology; 9; 1; 3-2014; 25-42
1776-2596
url http://hdl.handle.net/11336/8048
identifier_str_mv Cavaliere, Victoria; Papademetrio, Daniela Laura; Lombardo, Tomás; Costantino, Susana Nora; Blanco, Guillermo Armando C.; et al.; Caffeic acid phenylethyl ester and MG132, two novel nonconventional chemotherapeutic agents, induce apoptosis of human leukemic cells by disrupting mitochondrial function; Springer; Targeted Oncology; 9; 1; 3-2014; 25-42
1776-2596
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://link.springer.com/article/10.1007%2Fs11523-013-0256-y
info:eu-repo/semantics/altIdentifier/doi/10.1007/s11523-013-0256-y
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
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
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 13.070432

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