Antimetastatic, antineoplastic, and toxic effects of 4-hydroxycoumarin in a preclinical mouse melanoma model
Por:
Salinas-Jazmín N., De La Fuente M., Jaimez R., Pérez-Tapia M., Pérez-Torres A., Velasco-Velázquez M.A.
Publicada:
1 abr 2010
Resumen:
Purpose: We have previously reported that in vitro treatment of B16-F10 melanoma cells with 4-hydroxycoumarin (4-HC) decreases their metastatic potential. However, the antimetastatic efficacy of 4-HC in vivo is unknown; therefore, we investigated the antimetastatic and antineoplastic effects of 4-HC in a mouse melanoma model. Based on the findings, the immunomodulatory and toxic effects of 4-HC were also studied. Methods: Experimental metastasis assay was performed in C57BL/6 mice that received 4-HC before intravenous injection of B16-F10 cells. Antitumor and antimetastatic efficacy of 4-HC was assessed in mice implanted subcutaneously with melanoma cells. Possible immunostimulant and toxic effects of 4-HC were studied in healthy mice. Results: 4-HC reduced the number of experimental lung metastases. Moreover, 4-HC diminished primary tumor growth and increased survival time in mice bearing melanoma tumors. Treatments also decrease spontaneous lung metastases in the same animals. Different to other coumarins, the antitumor effect of 4-HC seems to be unrelated to immunostimulation, since plasma concentrations of cytokines remained unchanged. In contrast, toxic histological changes in nephrons and bronchiolar epithelium and a pronounced anticoagulant effect were found in 4-HC treated animals. Conclusions: These results show that 4-HC not only exhibit antimetastatic effect in vivo, but also effectively reduces tumor growth and improves survival, even when it produce toxic effects. Although the molecular mechanism of 4-HC actions needs to be further defined, our data suggest that 4-HC may lead to the development of agents that could be used as adjuvants in the therapy of melanoma. © 2009 Springer-Verlag.
Filiaciones:
Salinas-Jazmín N.:
Univ Nacl Autonoma Mexico, Fac Med, Dept Farmacol, Mexico City 04510, DF, Mexico
De La Fuente M.:
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala s/n, México, DF, Mexico
Jaimez R.:
Univ Nacl Autonoma Mexico, Fac Med, Dept Farmacol, Mexico City 04510, DF, Mexico
Pérez-Tapia M.:
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala s/n, México, DF, Mexico
Pérez-Torres A.:
Univ Nacl Autonoma Mexico, Fac Med, Dept Biol Celular & Tisular, Mexico City 04510, DF, Mexico
Velasco-Velázquez M.A.:
Univ Nacl Autonoma Mexico, Fac Med, Dept Farmacol, Mexico City 04510, DF, Mexico
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