Studies of the antitumor mechanism of action of dermaseptin B2, a multifunctional cationic antimicrobial peptide, reveal a partial implication of cell surface glycosaminoglycans

Autores
Dos Santos, Célia; Hamadat, Sabah; Le Saux, Karen; Newton, Clara; Mazouni, Meriem; Zargarian, Loussiné; Miro-Padovani, Mickael; Zadigue, Patricia; Delbé, Jean; Hamma-Kourbali, Yamina; Amiche, Mohamed
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Dermaseptin-B2 (DRS-B2) is a multifunctional cationic antimicrobial peptide (CAP) isolated from frog skin secretion. We previously reported that DRS-B2 possesses anticancer and antiangiogenic activities in vitro and in vivo. In the present study, we evaluated the antiproliferative activity of DRS-B2 on numerous tumor cell lines, its cell internalization and studies of its molecular partners as well as their influences on its structure. Confocal microscopy using ([Alexa594]-(Cys0)-DRS-B2) shows that in sensitive human tumor cells (PC3), DRS-B2 seems to accumulate rapidly at the cytoplasmic membranes and enters the cytoplasm and the nucleus, while in less sensitive tumor cells (U87MG), DRS-B2 is found packed in vesicles at the cell membrane. Furthermore FACS analysis shows that PC3 cells viability decreases after DRS-B2 treatment while U87 MG seems to be unaffected. However, "pull down" experiments performed with total protein pools from PC3 or U87MG cells and the comparison between the antiproliferative effect of DRS-B2 and its synthetic analog containing all Damino acids suggest the absence of a stereo-selective protein receptor. Pretreatment of PC3 cells with sodium chlorate, decreases the antiproliferative activity of DRS-B2. This activity is partially restored after addition of exogenous chondroitin sulfate C (CS-C). Moreover, we demonstrate that at nanomolar concentrations CS-C potentiates the antiproliferative effect of DRS-B2. These results highlight the partial implication of glycosaminoglycans in the mechanism of antiproliferative action of DRS-B2. Structural analysis of DRS-B2 by circular dichroism in the presence of increasing concentration of CS-C shows that DRS-B2 adopts anα-helical structure. Finally, structure-activity-relationship studies suggest a key role of the W residue in position 3 of the DRS-B2 sequence for its antiproliferative activity.


Fil: Dos Santos, Célia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centre National de la Recherche Scientifique; Francia
Fil: Hamadat, Sabah. Centre National de la Recherche Scientifique; Francia. University Paris Est Creteil; Francia
Fil: Le Saux, Karen. University Paris Est Creteil; Francia
Fil: Newton, Clara. Centre National de la Recherche Scientifique; Francia. University Paris Est Creteil; Francia
Fil: Mazouni, Meriem. Centre National de la Recherche Scientifique; Francia. University Paris Est Creteil; Francia
Fil: Zargarian, Loussiné. Centre National de la Recherche Scientifique; Francia
Fil: Miro-Padovani, Mickael. University Paris Est Creteil; Francia
Fil: Zadigue, Patricia. University Paris Est Creteil; Francia
Fil: Delbé, Jean. University Paris Est Creteil; Francia
Fil: Hamma-Kourbali, Yamina. University Paris Est Creteil; Francia
Fil: Amiche, Mohamed. University Paris Est Creteil; Francia
Materia
DERMASEPTIN B2
ANTITUMORAL ACTIVITY
GLYCOSAMINOGLYCANS
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:11336/41470
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/41470
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Studies of the antitumor mechanism of action of dermaseptin B2, a multifunctional cationic antimicrobial peptide, reveal a partial implication of cell surface glycosaminoglycansDos Santos, CéliaHamadat, SabahLe Saux, KarenNewton, ClaraMazouni, MeriemZargarian, LoussinéMiro-Padovani, MickaelZadigue, PatriciaDelbé, JeanHamma-Kourbali, YaminaAmiche, MohamedDERMASEPTIN B2ANTITUMORAL ACTIVITYGLYCOSAMINOGLYCANShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Dermaseptin-B2 (DRS-B2) is a multifunctional cationic antimicrobial peptide (CAP) isolated from frog skin secretion. We previously reported that DRS-B2 possesses anticancer and antiangiogenic activities in vitro and in vivo. In the present study, we evaluated the antiproliferative activity of DRS-B2 on numerous tumor cell lines, its cell internalization and studies of its molecular partners as well as their influences on its structure. Confocal microscopy using ([Alexa594]-(Cys0)-DRS-B2) shows that in sensitive human tumor cells (PC3), DRS-B2 seems to accumulate rapidly at the cytoplasmic membranes and enters the cytoplasm and the nucleus, while in less sensitive tumor cells (U87MG), DRS-B2 is found packed in vesicles at the cell membrane. Furthermore FACS analysis shows that PC3 cells viability decreases after DRS-B2 treatment while U87 MG seems to be unaffected. However, "pull down" experiments performed with total protein pools from PC3 or U87MG cells and the comparison between the antiproliferative effect of DRS-B2 and its synthetic analog containing all Damino acids suggest the absence of a stereo-selective protein receptor. Pretreatment of PC3 cells with sodium chlorate, decreases the antiproliferative activity of DRS-B2. This activity is partially restored after addition of exogenous chondroitin sulfate C (CS-C). Moreover, we demonstrate that at nanomolar concentrations CS-C potentiates the antiproliferative effect of DRS-B2. These results highlight the partial implication of glycosaminoglycans in the mechanism of antiproliferative action of DRS-B2. Structural analysis of DRS-B2 by circular dichroism in the presence of increasing concentration of CS-C shows that DRS-B2 adopts anα-helical structure. Finally, structure-activity-relationship studies suggest a key role of the W residue in position 3 of the DRS-B2 sequence for its antiproliferative activity.<br /><br />Fil: Dos Santos, Célia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centre National de la Recherche Scientifique; FranciaFil: Hamadat, Sabah. Centre National de la Recherche Scientifique; Francia. University Paris Est Creteil; FranciaFil: Le Saux, Karen. University Paris Est Creteil; FranciaFil: Newton, Clara. Centre National de la Recherche Scientifique; Francia. University Paris Est Creteil; FranciaFil: Mazouni, Meriem. Centre National de la Recherche Scientifique; Francia. University Paris Est Creteil; FranciaFil: Zargarian, Loussiné. Centre National de la Recherche Scientifique; FranciaFil: Miro-Padovani, Mickael. University Paris Est Creteil; FranciaFil: Zadigue, Patricia. University Paris Est Creteil; FranciaFil: Delbé, Jean. University Paris Est Creteil; FranciaFil: Hamma-Kourbali, Yamina. University Paris Est Creteil; FranciaFil: Amiche, Mohamed. University Paris Est Creteil; FranciaPublic Library of Science2017-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/41470Dos Santos, Célia; Hamadat, Sabah; Le Saux, Karen; Newton, Clara; Mazouni, Meriem; et al.; Studies of the antitumor mechanism of action of dermaseptin B2, a multifunctional cationic antimicrobial peptide, reveal a partial implication of cell surface glycosaminoglycans; Public Library of Science; Plos One; 12; 8; 8-20171932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0182926info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182926info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:10Zoai:ri.conicet.gov.ar:11336/41470instacron: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 10:11:10.971CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Studies of the antitumor mechanism of action of dermaseptin B2, a multifunctional cationic antimicrobial peptide, reveal a partial implication of cell surface glycosaminoglycans
title Studies of the antitumor mechanism of action of dermaseptin B2, a multifunctional cationic antimicrobial peptide, reveal a partial implication of cell surface glycosaminoglycans
spellingShingle Studies of the antitumor mechanism of action of dermaseptin B2, a multifunctional cationic antimicrobial peptide, reveal a partial implication of cell surface glycosaminoglycans
Dos Santos, Célia
DERMASEPTIN B2
ANTITUMORAL ACTIVITY
GLYCOSAMINOGLYCANS
title_short Studies of the antitumor mechanism of action of dermaseptin B2, a multifunctional cationic antimicrobial peptide, reveal a partial implication of cell surface glycosaminoglycans
title_full Studies of the antitumor mechanism of action of dermaseptin B2, a multifunctional cationic antimicrobial peptide, reveal a partial implication of cell surface glycosaminoglycans
title_fullStr Studies of the antitumor mechanism of action of dermaseptin B2, a multifunctional cationic antimicrobial peptide, reveal a partial implication of cell surface glycosaminoglycans
title_full_unstemmed Studies of the antitumor mechanism of action of dermaseptin B2, a multifunctional cationic antimicrobial peptide, reveal a partial implication of cell surface glycosaminoglycans
title_sort Studies of the antitumor mechanism of action of dermaseptin B2, a multifunctional cationic antimicrobial peptide, reveal a partial implication of cell surface glycosaminoglycans
dc.creator.none.fl_str_mv Dos Santos, Célia
Hamadat, Sabah
Le Saux, Karen
Newton, Clara
Mazouni, Meriem
Zargarian, Loussiné
Miro-Padovani, Mickael
Zadigue, Patricia
Delbé, Jean
Hamma-Kourbali, Yamina
Amiche, Mohamed
author Dos Santos, Célia
author_facet Dos Santos, Célia
Hamadat, Sabah
Le Saux, Karen
Newton, Clara
Mazouni, Meriem
Zargarian, Loussiné
Miro-Padovani, Mickael
Zadigue, Patricia
Delbé, Jean
Hamma-Kourbali, Yamina
Amiche, Mohamed
author_role author
author2 Hamadat, Sabah
Le Saux, Karen
Newton, Clara
Mazouni, Meriem
Zargarian, Loussiné
Miro-Padovani, Mickael
Zadigue, Patricia
Delbé, Jean
Hamma-Kourbali, Yamina
Amiche, Mohamed
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DERMASEPTIN B2
ANTITUMORAL ACTIVITY
GLYCOSAMINOGLYCANS
topic DERMASEPTIN B2
ANTITUMORAL ACTIVITY
GLYCOSAMINOGLYCANS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Dermaseptin-B2 (DRS-B2) is a multifunctional cationic antimicrobial peptide (CAP) isolated from frog skin secretion. We previously reported that DRS-B2 possesses anticancer and antiangiogenic activities in vitro and in vivo. In the present study, we evaluated the antiproliferative activity of DRS-B2 on numerous tumor cell lines, its cell internalization and studies of its molecular partners as well as their influences on its structure. Confocal microscopy using ([Alexa594]-(Cys0)-DRS-B2) shows that in sensitive human tumor cells (PC3), DRS-B2 seems to accumulate rapidly at the cytoplasmic membranes and enters the cytoplasm and the nucleus, while in less sensitive tumor cells (U87MG), DRS-B2 is found packed in vesicles at the cell membrane. Furthermore FACS analysis shows that PC3 cells viability decreases after DRS-B2 treatment while U87 MG seems to be unaffected. However, "pull down" experiments performed with total protein pools from PC3 or U87MG cells and the comparison between the antiproliferative effect of DRS-B2 and its synthetic analog containing all Damino acids suggest the absence of a stereo-selective protein receptor. Pretreatment of PC3 cells with sodium chlorate, decreases the antiproliferative activity of DRS-B2. This activity is partially restored after addition of exogenous chondroitin sulfate C (CS-C). Moreover, we demonstrate that at nanomolar concentrations CS-C potentiates the antiproliferative effect of DRS-B2. These results highlight the partial implication of glycosaminoglycans in the mechanism of antiproliferative action of DRS-B2. Structural analysis of DRS-B2 by circular dichroism in the presence of increasing concentration of CS-C shows that DRS-B2 adopts anα-helical structure. Finally, structure-activity-relationship studies suggest a key role of the W residue in position 3 of the DRS-B2 sequence for its antiproliferative activity.<br /><br />
Fil: Dos Santos, Célia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centre National de la Recherche Scientifique; Francia
Fil: Hamadat, Sabah. Centre National de la Recherche Scientifique; Francia. University Paris Est Creteil; Francia
Fil: Le Saux, Karen. University Paris Est Creteil; Francia
Fil: Newton, Clara. Centre National de la Recherche Scientifique; Francia. University Paris Est Creteil; Francia
Fil: Mazouni, Meriem. Centre National de la Recherche Scientifique; Francia. University Paris Est Creteil; Francia
Fil: Zargarian, Loussiné. Centre National de la Recherche Scientifique; Francia
Fil: Miro-Padovani, Mickael. University Paris Est Creteil; Francia
Fil: Zadigue, Patricia. University Paris Est Creteil; Francia
Fil: Delbé, Jean. University Paris Est Creteil; Francia
Fil: Hamma-Kourbali, Yamina. University Paris Est Creteil; Francia
Fil: Amiche, Mohamed. University Paris Est Creteil; Francia
description Dermaseptin-B2 (DRS-B2) is a multifunctional cationic antimicrobial peptide (CAP) isolated from frog skin secretion. We previously reported that DRS-B2 possesses anticancer and antiangiogenic activities in vitro and in vivo. In the present study, we evaluated the antiproliferative activity of DRS-B2 on numerous tumor cell lines, its cell internalization and studies of its molecular partners as well as their influences on its structure. Confocal microscopy using ([Alexa594]-(Cys0)-DRS-B2) shows that in sensitive human tumor cells (PC3), DRS-B2 seems to accumulate rapidly at the cytoplasmic membranes and enters the cytoplasm and the nucleus, while in less sensitive tumor cells (U87MG), DRS-B2 is found packed in vesicles at the cell membrane. Furthermore FACS analysis shows that PC3 cells viability decreases after DRS-B2 treatment while U87 MG seems to be unaffected. However, "pull down" experiments performed with total protein pools from PC3 or U87MG cells and the comparison between the antiproliferative effect of DRS-B2 and its synthetic analog containing all Damino acids suggest the absence of a stereo-selective protein receptor. Pretreatment of PC3 cells with sodium chlorate, decreases the antiproliferative activity of DRS-B2. This activity is partially restored after addition of exogenous chondroitin sulfate C (CS-C). Moreover, we demonstrate that at nanomolar concentrations CS-C potentiates the antiproliferative effect of DRS-B2. These results highlight the partial implication of glycosaminoglycans in the mechanism of antiproliferative action of DRS-B2. Structural analysis of DRS-B2 by circular dichroism in the presence of increasing concentration of CS-C shows that DRS-B2 adopts anα-helical structure. Finally, structure-activity-relationship studies suggest a key role of the W residue in position 3 of the DRS-B2 sequence for its antiproliferative activity.<br /><br />
publishDate 2017
dc.date.none.fl_str_mv 2017-08
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/11336/41470
Dos Santos, Célia; Hamadat, Sabah; Le Saux, Karen; Newton, Clara; Mazouni, Meriem; et al.; Studies of the antitumor mechanism of action of dermaseptin B2, a multifunctional cationic antimicrobial peptide, reveal a partial implication of cell surface glycosaminoglycans; Public Library of Science; Plos One; 12; 8; 8-2017
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/41470
identifier_str_mv Dos Santos, Célia; Hamadat, Sabah; Le Saux, Karen; Newton, Clara; Mazouni, Meriem; et al.; Studies of the antitumor mechanism of action of dermaseptin B2, a multifunctional cationic antimicrobial peptide, reveal a partial implication of cell surface glycosaminoglycans; Public Library of Science; Plos One; 12; 8; 8-2017
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0182926
info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182926
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 Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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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