Antitumor activity of histamine and clozapine in a mouse experimental model of human melanoma

Autores
Massari, Noelia Andrea; Medina, Vanina Araceli; Cricco, Graciela Patricia; Martinel Lamas, Diego José; Sambuco, Lorena Andrea; Pagotto, Romina; Ventura, Clara; Ciraolo, Pablo Juan; Pignataro, Omar Pedro; Bergoc, Rosa Maria; Rivera, Elena Susana
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Functional presence of histamine H4 receptor (H4R) was demonstrated in human melanoma cell lines and biopsies. Objective: The purposes of this work were to investigate signal transduction pathways and biological responses triggered by the activation of H4R in human primary (WM35) and metastatic (M1/15) melanoma cell lines and to evaluate the in vivo antitumor activity of histamine (HA) and clozapine (CLZ) on human M1/15 melanoma xenografts. Methods: Clonogenic assay, incorporation of BrdU, cell cycle distribution, phosphorylation levels of ERK1/2 and cAMP production were evaluated in vitro. An experimental human melanoma model was developed into athymic nude mice. Tumor growth, survival and histochemical studies were performed in order to investigate the expression levels of H4R, HA, PCNA, mitotic index (MI), and angiogenesis. Results: The results indicate that H4R agonists inhibited forskolin-induced cAMP levels only in M1/15 cells while increased phosphorylation levels of ERK1/2 and decreased proliferation in both cell types. In vivo studies show that HA and CLZ (1mgkg-1, sc) significantly increased median survival and decreased tumor volume. These effects were associated to a reduction in MI, in the expression of proliferation marker and in intratumoral neovascularization. Conclusions: We conclude that HA and CLZ exhibit an antitumoral effect in vitro and in vivo on human melanoma, suggesting the therapeutic potential of these compounds for the treatment of malignant melanoma.
Fil: Massari, Noelia Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Medina, Vanina Araceli. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cricco, Graciela Patricia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Martinel Lamas, Diego José. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sambuco, Lorena Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pagotto, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Ventura, Clara. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ciraolo, Pablo Juan. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina
Fil: Pignataro, Omar Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Bergoc, Rosa Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina
Fil: Rivera, Elena Susana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina
Materia
ERK1/2
H4R
HISTAMINE
MELANOMA
PROLIFERATION
SURVIVAL
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:11336/1785
Acceder
id CONICETDig_0fa2947b48caff6765d3500669d3ea63
oai_identifier_str oai:ri.conicet.gov.ar:11336/1785
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Antitumor activity of histamine and clozapine in a mouse experimental model of human melanomaMassari, Noelia AndreaMedina, Vanina AraceliCricco, Graciela PatriciaMartinel Lamas, Diego JoséSambuco, Lorena AndreaPagotto, RominaVentura, ClaraCiraolo, Pablo JuanPignataro, Omar PedroBergoc, Rosa MariaRivera, Elena SusanaERK1/2H4RHISTAMINEMELANOMAPROLIFERATIONSURVIVALhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Background: Functional presence of histamine H4 receptor (H4R) was demonstrated in human melanoma cell lines and biopsies. Objective: The purposes of this work were to investigate signal transduction pathways and biological responses triggered by the activation of H4R in human primary (WM35) and metastatic (M1/15) melanoma cell lines and to evaluate the in vivo antitumor activity of histamine (HA) and clozapine (CLZ) on human M1/15 melanoma xenografts. Methods: Clonogenic assay, incorporation of BrdU, cell cycle distribution, phosphorylation levels of ERK1/2 and cAMP production were evaluated in vitro. An experimental human melanoma model was developed into athymic nude mice. Tumor growth, survival and histochemical studies were performed in order to investigate the expression levels of H4R, HA, PCNA, mitotic index (MI), and angiogenesis. Results: The results indicate that H4R agonists inhibited forskolin-induced cAMP levels only in M1/15 cells while increased phosphorylation levels of ERK1/2 and decreased proliferation in both cell types. In vivo studies show that HA and CLZ (1mgkg-1, sc) significantly increased median survival and decreased tumor volume. These effects were associated to a reduction in MI, in the expression of proliferation marker and in intratumoral neovascularization. Conclusions: We conclude that HA and CLZ exhibit an antitumoral effect in vitro and in vivo on human melanoma, suggesting the therapeutic potential of these compounds for the treatment of malignant melanoma.Fil: Massari, Noelia Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Medina, Vanina Araceli. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cricco, Graciela Patricia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martinel Lamas, Diego José. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sambuco, Lorena Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pagotto, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Ventura, Clara. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ciraolo, Pablo Juan. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; ArgentinaFil: Pignataro, Omar Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Bergoc, Rosa Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; ArgentinaFil: Rivera, Elena Susana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; ArgentinaElsevier Ireland2013-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/1785Massari, Noelia Andrea; Medina, Vanina Araceli; Cricco, Graciela Patricia; Martinel Lamas, Diego José; Sambuco, Lorena Andrea; et al.; Antitumor activity of histamine and clozapine in a mouse experimental model of human melanoma; Elsevier Ireland; Journal of Dermatological Science; 72; 3; 12-2013; 252-2620923-1811enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0923181113002715info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jdermsci.2013.07.012info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:58:07Zoai:ri.conicet.gov.ar:11336/1785instacron: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 14:58:08.172CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Antitumor activity of histamine and clozapine in a mouse experimental model of human melanoma
title Antitumor activity of histamine and clozapine in a mouse experimental model of human melanoma
spellingShingle Antitumor activity of histamine and clozapine in a mouse experimental model of human melanoma
Massari, Noelia Andrea
ERK1/2
H4R
HISTAMINE
MELANOMA
PROLIFERATION
SURVIVAL
title_short Antitumor activity of histamine and clozapine in a mouse experimental model of human melanoma
title_full Antitumor activity of histamine and clozapine in a mouse experimental model of human melanoma
title_fullStr Antitumor activity of histamine and clozapine in a mouse experimental model of human melanoma
title_full_unstemmed Antitumor activity of histamine and clozapine in a mouse experimental model of human melanoma
title_sort Antitumor activity of histamine and clozapine in a mouse experimental model of human melanoma
dc.creator.none.fl_str_mv Massari, Noelia Andrea
Medina, Vanina Araceli
Cricco, Graciela Patricia
Martinel Lamas, Diego José
Sambuco, Lorena Andrea
Pagotto, Romina
Ventura, Clara
Ciraolo, Pablo Juan
Pignataro, Omar Pedro
Bergoc, Rosa Maria
Rivera, Elena Susana
author Massari, Noelia Andrea
author_facet Massari, Noelia Andrea
Medina, Vanina Araceli
Cricco, Graciela Patricia
Martinel Lamas, Diego José
Sambuco, Lorena Andrea
Pagotto, Romina
Ventura, Clara
Ciraolo, Pablo Juan
Pignataro, Omar Pedro
Bergoc, Rosa Maria
Rivera, Elena Susana
author_role author
author2 Medina, Vanina Araceli
Cricco, Graciela Patricia
Martinel Lamas, Diego José
Sambuco, Lorena Andrea
Pagotto, Romina
Ventura, Clara
Ciraolo, Pablo Juan
Pignataro, Omar Pedro
Bergoc, Rosa Maria
Rivera, Elena Susana
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ERK1/2
H4R
HISTAMINE
MELANOMA
PROLIFERATION
SURVIVAL
topic ERK1/2
H4R
HISTAMINE
MELANOMA
PROLIFERATION
SURVIVAL
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Functional presence of histamine H4 receptor (H4R) was demonstrated in human melanoma cell lines and biopsies. Objective: The purposes of this work were to investigate signal transduction pathways and biological responses triggered by the activation of H4R in human primary (WM35) and metastatic (M1/15) melanoma cell lines and to evaluate the in vivo antitumor activity of histamine (HA) and clozapine (CLZ) on human M1/15 melanoma xenografts. Methods: Clonogenic assay, incorporation of BrdU, cell cycle distribution, phosphorylation levels of ERK1/2 and cAMP production were evaluated in vitro. An experimental human melanoma model was developed into athymic nude mice. Tumor growth, survival and histochemical studies were performed in order to investigate the expression levels of H4R, HA, PCNA, mitotic index (MI), and angiogenesis. Results: The results indicate that H4R agonists inhibited forskolin-induced cAMP levels only in M1/15 cells while increased phosphorylation levels of ERK1/2 and decreased proliferation in both cell types. In vivo studies show that HA and CLZ (1mgkg-1, sc) significantly increased median survival and decreased tumor volume. These effects were associated to a reduction in MI, in the expression of proliferation marker and in intratumoral neovascularization. Conclusions: We conclude that HA and CLZ exhibit an antitumoral effect in vitro and in vivo on human melanoma, suggesting the therapeutic potential of these compounds for the treatment of malignant melanoma.
Fil: Massari, Noelia Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Medina, Vanina Araceli. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cricco, Graciela Patricia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Martinel Lamas, Diego José. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sambuco, Lorena Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pagotto, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Ventura, Clara. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ciraolo, Pablo Juan. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina
Fil: Pignataro, Omar Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Bergoc, Rosa Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina
Fil: Rivera, Elena Susana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina
description Background: Functional presence of histamine H4 receptor (H4R) was demonstrated in human melanoma cell lines and biopsies. Objective: The purposes of this work were to investigate signal transduction pathways and biological responses triggered by the activation of H4R in human primary (WM35) and metastatic (M1/15) melanoma cell lines and to evaluate the in vivo antitumor activity of histamine (HA) and clozapine (CLZ) on human M1/15 melanoma xenografts. Methods: Clonogenic assay, incorporation of BrdU, cell cycle distribution, phosphorylation levels of ERK1/2 and cAMP production were evaluated in vitro. An experimental human melanoma model was developed into athymic nude mice. Tumor growth, survival and histochemical studies were performed in order to investigate the expression levels of H4R, HA, PCNA, mitotic index (MI), and angiogenesis. Results: The results indicate that H4R agonists inhibited forskolin-induced cAMP levels only in M1/15 cells while increased phosphorylation levels of ERK1/2 and decreased proliferation in both cell types. In vivo studies show that HA and CLZ (1mgkg-1, sc) significantly increased median survival and decreased tumor volume. These effects were associated to a reduction in MI, in the expression of proliferation marker and in intratumoral neovascularization. Conclusions: We conclude that HA and CLZ exhibit an antitumoral effect in vitro and in vivo on human melanoma, suggesting the therapeutic potential of these compounds for the treatment of malignant melanoma.
publishDate 2013
dc.date.none.fl_str_mv 2013-12
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/11336/1785
Massari, Noelia Andrea; Medina, Vanina Araceli; Cricco, Graciela Patricia; Martinel Lamas, Diego José; Sambuco, Lorena Andrea; et al.; Antitumor activity of histamine and clozapine in a mouse experimental model of human melanoma; Elsevier Ireland; Journal of Dermatological Science; 72; 3; 12-2013; 252-262
0923-1811
url http://hdl.handle.net/11336/1785
identifier_str_mv Massari, Noelia Andrea; Medina, Vanina Araceli; Cricco, Graciela Patricia; Martinel Lamas, Diego José; Sambuco, Lorena Andrea; et al.; Antitumor activity of histamine and clozapine in a mouse experimental model of human melanoma; Elsevier Ireland; Journal of Dermatological Science; 72; 3; 12-2013; 252-262
0923-1811
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0923181113002715
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jdermsci.2013.07.012
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 Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
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 13.221938

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