Artículo

Massari, N.A.; Medina, V.A.; Cricco, G.P.; Martinel Lamas, D.J.; Sambuco, L.; Pagotto, R.; Ventura, C.; Ciraolo, P.J.; Pignataro, O.; Bergoc, R.M.; Rivera, E.S. "Antitumor activity of histamine and clozapine in a mouse experimental model of human melanoma" (2013) Journal of Dermatological Science. 72(3):252-262
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Abstract:

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. © 2013 Japanese Society for Investigative Dermatology.

Registro:

Documento: Artículo
Título:Antitumor activity of histamine and clozapine in a mouse experimental model of human melanoma
Autor:Massari, N.A.; Medina, V.A.; Cricco, G.P.; Martinel Lamas, D.J.; Sambuco, L.; Pagotto, R.; Ventura, C.; Ciraolo, P.J.; Pignataro, O.; Bergoc, R.M.; Rivera, E.S.
Filiación:Laboratory of Radioisotopes, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires 1113, Argentina
National Scientific and Technical Research Council (Conicet), Buenos Aires, Argentina
Institute of Immunooncology, Buenos Aires, Argentina
Laboratory of Molecular Endocrinology and Signal Transduction, Institute of Biology and Experimental Medicine-Conicet, Buenos Aires 1428, Argentina
Palabras clave:ERK1/2; H4R; Histamine; Melanoma; Proliferation; Survival; 1 (5 chloro 2 indolylcarbonyl) 4 methylpiperazine; 1 [2 (amidinothio)ethyl]guanidine; 2 [(aminoiminomethyl)amino]ethyl carbamimidothioic acid ester dihydrobromide; broxuridine; cell marker; clozapine; cyclic AMP; forskolin; histamine; histamine agonist; histamine H4 receptor; histamine receptor; mitogen activated protein kinase 1; mitogen activated protein kinase 3; unclassified drug; animal experiment; animal model; animal tissue; antineoplastic activity; article; cancer survival; cell line; cell proliferation; cellular distribution; clonogenic assay; concentration response; controlled study; drug screening; enzyme phosphorylation; histochemistry; human; human cell; IC 50; in vitro study; in vivo study; intracellular signaling; male; melanoma; melanoma cell; metastatic melanoma; mitosis index; mouse; nonhuman; primary tumor; priority journal; protein expression; protein induction; protein synthesis; treatment response; tumor growth; tumor vascularization; tumor volume; tumor xenograft; ERK1/2; H(4)R; Histamine; Melanoma; Proliferation; Survival; Animals; Cell Line, Tumor; Cell Proliferation; Clozapine; Cyclic AMP; Extracellular Signal-Regulated MAP Kinases; Histamine; Humans; Male; Melanoma, Experimental; Mice; Mice, Nude; Neovascularization, Pathologic; Phosphorylation; Receptors, G-Protein-Coupled; Receptors, Histamine; Signal Transduction; Xenograft Model Antitumor Assays
Año:2013
Volumen:72
Número:3
Página de inicio:252
Página de fin:262
DOI: http://dx.doi.org/10.1016/j.jdermsci.2013.07.012
Título revista:Journal of Dermatological Science
Título revista abreviado:J. Dermatol. Sci.
ISSN:09231811
CODEN:JDSCE
CAS:broxuridine, 59-14-3; clozapine, 5786-21-0; cyclic AMP, 60-92-4; forskolin, 66575-29-9; histamine, 51-45-6, 56-92-8, 93443-21-1; histamine H4 receptor, 272100-58-0; mitogen activated protein kinase 1, 137632-08-7; mitogen activated protein kinase 3, 137632-07-6
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09231811_v72_n3_p252_Massari

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Citas:

---------- APA ----------
Massari, N.A., Medina, V.A., Cricco, G.P., Martinel Lamas, D.J., Sambuco, L., Pagotto, R., Ventura, C.,..., Rivera, E.S. (2013) . Antitumor activity of histamine and clozapine in a mouse experimental model of human melanoma. Journal of Dermatological Science, 72(3), 252-262.
http://dx.doi.org/10.1016/j.jdermsci.2013.07.012
---------- CHICAGO ----------
Massari, N.A., Medina, V.A., Cricco, G.P., Martinel Lamas, D.J., Sambuco, L., Pagotto, R., et al. "Antitumor activity of histamine and clozapine in a mouse experimental model of human melanoma" . Journal of Dermatological Science 72, no. 3 (2013) : 252-262.
http://dx.doi.org/10.1016/j.jdermsci.2013.07.012
---------- MLA ----------
Massari, N.A., Medina, V.A., Cricco, G.P., Martinel Lamas, D.J., Sambuco, L., Pagotto, R., et al. "Antitumor activity of histamine and clozapine in a mouse experimental model of human melanoma" . Journal of Dermatological Science, vol. 72, no. 3, 2013, pp. 252-262.
http://dx.doi.org/10.1016/j.jdermsci.2013.07.012
---------- VANCOUVER ----------
Massari, N.A., Medina, V.A., Cricco, G.P., Martinel Lamas, D.J., Sambuco, L., Pagotto, R., et al. Antitumor activity of histamine and clozapine in a mouse experimental model of human melanoma. J. Dermatol. Sci. 2013;72(3):252-262.
http://dx.doi.org/10.1016/j.jdermsci.2013.07.012