A short caspase-3 isoform inhibits chemotherapy-induced apoptosis by blocking apoptosome assembly.

Alternative splicing of caspase-3 produces a short isoform caspase-3s that antagonizes caspase-3 apoptotic activity. However, the mechanism of apoptosis inhibition by caspase-3s remains unknown. Here we show that exogenous caspase-3 sensitizes MCF-7 and HBL100 breast cancers cells to chemotherapeuti...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Frédérique Végran, Romain Boidot, Eric Solary, Sarab Lizard-Nacol
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/09e2da4b770b4dda8ed5d1c67c51d403
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:09e2da4b770b4dda8ed5d1c67c51d403
record_format	dspace
spelling	oai:doaj.org-article:09e2da4b770b4dda8ed5d1c67c51d4032021-11-18T07:31:37ZA short caspase-3 isoform inhibits chemotherapy-induced apoptosis by blocking apoptosome assembly.1932-620310.1371/journal.pone.0029058https://doaj.org/article/09e2da4b770b4dda8ed5d1c67c51d4032011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22216167/?tool=EBIhttps://doaj.org/toc/1932-6203Alternative splicing of caspase-3 produces a short isoform caspase-3s that antagonizes caspase-3 apoptotic activity. However, the mechanism of apoptosis inhibition by caspase-3s remains unknown. Here we show that exogenous caspase-3 sensitizes MCF-7 and HBL100 breast cancers cells to chemotherapeutic treatments such as etoposide and methotrexate whereas co-transfection with caspase-3s strongly inhibits etoposide and methotrexate-induced apoptosis underlying thus the anti-apoptotic role of caspase-3s. In caspase-3 transfected cells, lamin-A and α-fodrin were cleaved when caspase-3 was activated by etoposide or methotrexate. When caspase-3s was co-transfected, this cleavage was strongly reduced. Depletion of caspase-3 by RNA interference in HBL100 containing endogenous caspase-3s caused reduction in etoposide and methotrexate-induced apoptosis, whereas the depletion of caspase-3s sensitized cells to chemotherapy. In the presence of caspase-3s, a lack of interaction between caspase-3 and caspase-9 was observed. Immunoprecipitation assays showed that caspase-3s binds the pro-forms of caspase-3. This result suggested that the absence of interaction with caspase-9 when both variants of caspase-3 are present contribute to block the apoptosome assembly and inhibit apoptosis. These data support that caspases-3s negatively interferes with caspase-3 activation and apoptosis in breast cancer, and that it can play key roles in the modulation of response to chemotherapeutic treatments.Frédérique VégranRomain BoidotEric SolarySarab Lizard-NacolPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e29058 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Frédérique Végran Romain Boidot Eric Solary Sarab Lizard-Nacol A short caspase-3 isoform inhibits chemotherapy-induced apoptosis by blocking apoptosome assembly.
description	Alternative splicing of caspase-3 produces a short isoform caspase-3s that antagonizes caspase-3 apoptotic activity. However, the mechanism of apoptosis inhibition by caspase-3s remains unknown. Here we show that exogenous caspase-3 sensitizes MCF-7 and HBL100 breast cancers cells to chemotherapeutic treatments such as etoposide and methotrexate whereas co-transfection with caspase-3s strongly inhibits etoposide and methotrexate-induced apoptosis underlying thus the anti-apoptotic role of caspase-3s. In caspase-3 transfected cells, lamin-A and α-fodrin were cleaved when caspase-3 was activated by etoposide or methotrexate. When caspase-3s was co-transfected, this cleavage was strongly reduced. Depletion of caspase-3 by RNA interference in HBL100 containing endogenous caspase-3s caused reduction in etoposide and methotrexate-induced apoptosis, whereas the depletion of caspase-3s sensitized cells to chemotherapy. In the presence of caspase-3s, a lack of interaction between caspase-3 and caspase-9 was observed. Immunoprecipitation assays showed that caspase-3s binds the pro-forms of caspase-3. This result suggested that the absence of interaction with caspase-9 when both variants of caspase-3 are present contribute to block the apoptosome assembly and inhibit apoptosis. These data support that caspases-3s negatively interferes with caspase-3 activation and apoptosis in breast cancer, and that it can play key roles in the modulation of response to chemotherapeutic treatments.
format	article
author	Frédérique Végran Romain Boidot Eric Solary Sarab Lizard-Nacol
author_facet	Frédérique Végran Romain Boidot Eric Solary Sarab Lizard-Nacol
author_sort	Frédérique Végran
title	A short caspase-3 isoform inhibits chemotherapy-induced apoptosis by blocking apoptosome assembly.
title_short	A short caspase-3 isoform inhibits chemotherapy-induced apoptosis by blocking apoptosome assembly.
title_full	A short caspase-3 isoform inhibits chemotherapy-induced apoptosis by blocking apoptosome assembly.
title_fullStr	A short caspase-3 isoform inhibits chemotherapy-induced apoptosis by blocking apoptosome assembly.
title_full_unstemmed	A short caspase-3 isoform inhibits chemotherapy-induced apoptosis by blocking apoptosome assembly.
title_sort	short caspase-3 isoform inhibits chemotherapy-induced apoptosis by blocking apoptosome assembly.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/09e2da4b770b4dda8ed5d1c67c51d403
work_keys_str_mv	AT frederiquevegran ashortcaspase3isoforminhibitschemotherapyinducedapoptosisbyblockingapoptosomeassembly AT romainboidot ashortcaspase3isoforminhibitschemotherapyinducedapoptosisbyblockingapoptosomeassembly AT ericsolary ashortcaspase3isoforminhibitschemotherapyinducedapoptosisbyblockingapoptosomeassembly AT sarablizardnacol ashortcaspase3isoforminhibitschemotherapyinducedapoptosisbyblockingapoptosomeassembly AT frederiquevegran shortcaspase3isoforminhibitschemotherapyinducedapoptosisbyblockingapoptosomeassembly AT romainboidot shortcaspase3isoforminhibitschemotherapyinducedapoptosisbyblockingapoptosomeassembly AT ericsolary shortcaspase3isoforminhibitschemotherapyinducedapoptosisbyblockingapoptosomeassembly AT sarablizardnacol shortcaspase3isoforminhibitschemotherapyinducedapoptosisbyblockingapoptosomeassembly
_version_	1718423330304819200

A short caspase-3 isoform inhibits chemotherapy-induced apoptosis by blocking apoptosome assembly.

Ejemplares similares