Preclinical efficacy of [V 4 Q 5 ]dDAVP, a second generation vasopressin analog, on metastatic spread and tumor-associated angiogenesis in colorectal cancer

Autores
Garona, Juan; Sobol, Natasha Tatiana; Pifano, Marina; Segatori, Valeria Inés; Gomez, Daniel Eduardo; Ripoll, Giselle Vanina; Alonso, Daniel Fernando
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Purpose Control of metastatic spread of colorectal cancer (CRC) remains as a major therapeutic challenge. [V 4 Q 5 ]dDAVP is a vasopressin peptide analog with previously reported anticancer activity against carcinoma tumors. By acting as a selective agonist of arginine vasopressin type 2 membrane receptor (AVPR2) present in endothelial and tumor cells, [V 4 Q 5 ]dDAVP is able to impair tumor aggressiveness and distant spread. Our aim was to evaluate the potential therapeutic benefits of [V 4 Q 5 ]dDAVP on highly aggressive CRC disease using experimental models with translational relevance. Materials and Methods Murine CT-26 and human Colo-205 AVPR2-expressing CRC cell lines were used to test the preclinical efficacy of [V 4 Q 5 ]dDAVP, both in vitro and in vivo. Results In syngeneic mice surgically implanted with CT-26 cells in the spleen, sustained intravenous treatment with [V 4 Q 5 ]dDAVP (0.3 jg/kg) dramatically impaired metastatic progression to liver without overt signs of toxicity, and also reduced experimental lung colonization. The compound inhibited in vivo angiogenesis driven by Colo-205 cells in athymic mice, as well as in vitro endothelial cell migration and capillary tube formation. [V 4 Q 5 ]dDAVP exerted AVPR2-dependent cytostatic activity in vitro (IC50 1.08 |jM) and addition to 5-fluorouracil resulted in synergistic antiproliferative effects both in CT-26 and Colo-205 cells. Conclusion The present preclinical study establishes for the first time the efficacy of [V 4 Q 5 ]dDAVP on CRC. These encouraging results suggest that the novel second generation vasopressin analog could be used for the management of aggressive CRC as an adjuvant agent during surgery or to complement standard chemotherapy, limiting tumor angiogenesis and metastasis and thus protecting the patient from CRC recurrence.
Fil: Garona, Juan. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sobol, Natasha Tatiana. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pifano, Marina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Segatori, Valeria Inés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ripoll, Giselle Vanina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
ADJUVANT THERAPY
ANTIANGIOGENIC
ANTIMETASTATIC
AVPR2
COMBINATIONAL THERAPY
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:11336/98540
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Preclinical efficacy of [V 4 Q 5 ]dDAVP, a second generation vasopressin analog, on metastatic spread and tumor-associated angiogenesis in colorectal cancerGarona, JuanSobol, Natasha TatianaPifano, MarinaSegatori, Valeria InésGomez, Daniel EduardoRipoll, Giselle VaninaAlonso, Daniel FernandoADJUVANT THERAPYANTIANGIOGENICANTIMETASTATICAVPR2COMBINATIONAL THERAPYhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Purpose Control of metastatic spread of colorectal cancer (CRC) remains as a major therapeutic challenge. [V 4 Q 5 ]dDAVP is a vasopressin peptide analog with previously reported anticancer activity against carcinoma tumors. By acting as a selective agonist of arginine vasopressin type 2 membrane receptor (AVPR2) present in endothelial and tumor cells, [V 4 Q 5 ]dDAVP is able to impair tumor aggressiveness and distant spread. Our aim was to evaluate the potential therapeutic benefits of [V 4 Q 5 ]dDAVP on highly aggressive CRC disease using experimental models with translational relevance. Materials and Methods Murine CT-26 and human Colo-205 AVPR2-expressing CRC cell lines were used to test the preclinical efficacy of [V 4 Q 5 ]dDAVP, both in vitro and in vivo. Results In syngeneic mice surgically implanted with CT-26 cells in the spleen, sustained intravenous treatment with [V 4 Q 5 ]dDAVP (0.3 jg/kg) dramatically impaired metastatic progression to liver without overt signs of toxicity, and also reduced experimental lung colonization. The compound inhibited in vivo angiogenesis driven by Colo-205 cells in athymic mice, as well as in vitro endothelial cell migration and capillary tube formation. [V 4 Q 5 ]dDAVP exerted AVPR2-dependent cytostatic activity in vitro (IC50 1.08 |jM) and addition to 5-fluorouracil resulted in synergistic antiproliferative effects both in CT-26 and Colo-205 cells. Conclusion The present preclinical study establishes for the first time the efficacy of [V 4 Q 5 ]dDAVP on CRC. These encouraging results suggest that the novel second generation vasopressin analog could be used for the management of aggressive CRC as an adjuvant agent during surgery or to complement standard chemotherapy, limiting tumor angiogenesis and metastasis and thus protecting the patient from CRC recurrence.Fil: Garona, Juan. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sobol, Natasha Tatiana. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pifano, Marina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Segatori, Valeria Inés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ripoll, Giselle Vanina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaKorean Cancer Association2018-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/98540Garona, Juan; Sobol, Natasha Tatiana; Pifano, Marina; Segatori, Valeria Inés; Gomez, Daniel Eduardo; et al.; Preclinical efficacy of [V 4 Q 5 ]dDAVP, a second generation vasopressin analog, on metastatic spread and tumor-associated angiogenesis in colorectal cancer; Korean Cancer Association; Cancer Research and Treatment; 51; 2; 6-2018; 438-4502005-9256CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.e-crt.org/journal/view.php?doi=10.4143/crt.2018.040info:eu-repo/semantics/altIdentifier/doi/10.4143/crt.2018.040info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:44:04Zoai:ri.conicet.gov.ar:11336/98540instacron: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 09:44:04.345CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Preclinical efficacy of [V 4 Q 5 ]dDAVP, a second generation vasopressin analog, on metastatic spread and tumor-associated angiogenesis in colorectal cancer
title Preclinical efficacy of [V 4 Q 5 ]dDAVP, a second generation vasopressin analog, on metastatic spread and tumor-associated angiogenesis in colorectal cancer
spellingShingle Preclinical efficacy of [V 4 Q 5 ]dDAVP, a second generation vasopressin analog, on metastatic spread and tumor-associated angiogenesis in colorectal cancer
Garona, Juan
ADJUVANT THERAPY
ANTIANGIOGENIC
ANTIMETASTATIC
AVPR2
COMBINATIONAL THERAPY
title_short Preclinical efficacy of [V 4 Q 5 ]dDAVP, a second generation vasopressin analog, on metastatic spread and tumor-associated angiogenesis in colorectal cancer
title_full Preclinical efficacy of [V 4 Q 5 ]dDAVP, a second generation vasopressin analog, on metastatic spread and tumor-associated angiogenesis in colorectal cancer
title_fullStr Preclinical efficacy of [V 4 Q 5 ]dDAVP, a second generation vasopressin analog, on metastatic spread and tumor-associated angiogenesis in colorectal cancer
title_full_unstemmed Preclinical efficacy of [V 4 Q 5 ]dDAVP, a second generation vasopressin analog, on metastatic spread and tumor-associated angiogenesis in colorectal cancer
title_sort Preclinical efficacy of [V 4 Q 5 ]dDAVP, a second generation vasopressin analog, on metastatic spread and tumor-associated angiogenesis in colorectal cancer
dc.creator.none.fl_str_mv Garona, Juan
Sobol, Natasha Tatiana
Pifano, Marina
Segatori, Valeria Inés
Gomez, Daniel Eduardo
Ripoll, Giselle Vanina
Alonso, Daniel Fernando
author Garona, Juan
author_facet Garona, Juan
Sobol, Natasha Tatiana
Pifano, Marina
Segatori, Valeria Inés
Gomez, Daniel Eduardo
Ripoll, Giselle Vanina
Alonso, Daniel Fernando
author_role author
author2 Sobol, Natasha Tatiana
Pifano, Marina
Segatori, Valeria Inés
Gomez, Daniel Eduardo
Ripoll, Giselle Vanina
Alonso, Daniel Fernando
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ADJUVANT THERAPY
ANTIANGIOGENIC
ANTIMETASTATIC
AVPR2
COMBINATIONAL THERAPY
topic ADJUVANT THERAPY
ANTIANGIOGENIC
ANTIMETASTATIC
AVPR2
COMBINATIONAL THERAPY
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Purpose Control of metastatic spread of colorectal cancer (CRC) remains as a major therapeutic challenge. [V 4 Q 5 ]dDAVP is a vasopressin peptide analog with previously reported anticancer activity against carcinoma tumors. By acting as a selective agonist of arginine vasopressin type 2 membrane receptor (AVPR2) present in endothelial and tumor cells, [V 4 Q 5 ]dDAVP is able to impair tumor aggressiveness and distant spread. Our aim was to evaluate the potential therapeutic benefits of [V 4 Q 5 ]dDAVP on highly aggressive CRC disease using experimental models with translational relevance. Materials and Methods Murine CT-26 and human Colo-205 AVPR2-expressing CRC cell lines were used to test the preclinical efficacy of [V 4 Q 5 ]dDAVP, both in vitro and in vivo. Results In syngeneic mice surgically implanted with CT-26 cells in the spleen, sustained intravenous treatment with [V 4 Q 5 ]dDAVP (0.3 jg/kg) dramatically impaired metastatic progression to liver without overt signs of toxicity, and also reduced experimental lung colonization. The compound inhibited in vivo angiogenesis driven by Colo-205 cells in athymic mice, as well as in vitro endothelial cell migration and capillary tube formation. [V 4 Q 5 ]dDAVP exerted AVPR2-dependent cytostatic activity in vitro (IC50 1.08 |jM) and addition to 5-fluorouracil resulted in synergistic antiproliferative effects both in CT-26 and Colo-205 cells. Conclusion The present preclinical study establishes for the first time the efficacy of [V 4 Q 5 ]dDAVP on CRC. These encouraging results suggest that the novel second generation vasopressin analog could be used for the management of aggressive CRC as an adjuvant agent during surgery or to complement standard chemotherapy, limiting tumor angiogenesis and metastasis and thus protecting the patient from CRC recurrence.
Fil: Garona, Juan. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sobol, Natasha Tatiana. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pifano, Marina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Segatori, Valeria Inés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ripoll, Giselle Vanina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Purpose Control of metastatic spread of colorectal cancer (CRC) remains as a major therapeutic challenge. [V 4 Q 5 ]dDAVP is a vasopressin peptide analog with previously reported anticancer activity against carcinoma tumors. By acting as a selective agonist of arginine vasopressin type 2 membrane receptor (AVPR2) present in endothelial and tumor cells, [V 4 Q 5 ]dDAVP is able to impair tumor aggressiveness and distant spread. Our aim was to evaluate the potential therapeutic benefits of [V 4 Q 5 ]dDAVP on highly aggressive CRC disease using experimental models with translational relevance. Materials and Methods Murine CT-26 and human Colo-205 AVPR2-expressing CRC cell lines were used to test the preclinical efficacy of [V 4 Q 5 ]dDAVP, both in vitro and in vivo. Results In syngeneic mice surgically implanted with CT-26 cells in the spleen, sustained intravenous treatment with [V 4 Q 5 ]dDAVP (0.3 jg/kg) dramatically impaired metastatic progression to liver without overt signs of toxicity, and also reduced experimental lung colonization. The compound inhibited in vivo angiogenesis driven by Colo-205 cells in athymic mice, as well as in vitro endothelial cell migration and capillary tube formation. [V 4 Q 5 ]dDAVP exerted AVPR2-dependent cytostatic activity in vitro (IC50 1.08 |jM) and addition to 5-fluorouracil resulted in synergistic antiproliferative effects both in CT-26 and Colo-205 cells. Conclusion The present preclinical study establishes for the first time the efficacy of [V 4 Q 5 ]dDAVP on CRC. These encouraging results suggest that the novel second generation vasopressin analog could be used for the management of aggressive CRC as an adjuvant agent during surgery or to complement standard chemotherapy, limiting tumor angiogenesis and metastasis and thus protecting the patient from CRC recurrence.
publishDate 2018
dc.date.none.fl_str_mv 2018-06
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/11336/98540
Garona, Juan; Sobol, Natasha Tatiana; Pifano, Marina; Segatori, Valeria Inés; Gomez, Daniel Eduardo; et al.; Preclinical efficacy of [V 4 Q 5 ]dDAVP, a second generation vasopressin analog, on metastatic spread and tumor-associated angiogenesis in colorectal cancer; Korean Cancer Association; Cancer Research and Treatment; 51; 2; 6-2018; 438-450
2005-9256
CONICET Digital
CONICET
url http://hdl.handle.net/11336/98540
identifier_str_mv Garona, Juan; Sobol, Natasha Tatiana; Pifano, Marina; Segatori, Valeria Inés; Gomez, Daniel Eduardo; et al.; Preclinical efficacy of [V 4 Q 5 ]dDAVP, a second generation vasopressin analog, on metastatic spread and tumor-associated angiogenesis in colorectal cancer; Korean Cancer Association; Cancer Research and Treatment; 51; 2; 6-2018; 438-450
2005-9256
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.e-crt.org/journal/view.php?doi=10.4143/crt.2018.040
info:eu-repo/semantics/altIdentifier/doi/10.4143/crt.2018.040
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Korean Cancer Association
publisher.none.fl_str_mv Korean Cancer Association
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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