RESUMEN
The phenomenon of multiple primary malignant tumors (MPMT) is characterized by the presence of several primary neoplasms in the same patient. An experimental model of MPMT with one dominating tumor was developed. Female BALB/c nude mice received simultaneous subcutaneous inoculation of Guerin's carcinoma (5×105 tumor cells in 0.5 ml saline) and B16/F10 melanoma (0.5 ml suspension diluted 1:20 with saline). Control females received transplantation of either melanoma or carcinoma alone in the same doses and volumes. In animals with MPMT model, tumors appeared 3-fold faster than after isolated transplantation of melanoma or Guerin's carcinoma and were larger by 7.5 and 2.2 times, respectively; the survival of mice with MPMT was lower. Guerin's carcinoma in the MPMT model metastasized to melanoma and almost completely suppressed its growth. Thus, a MPMT model was created with carcinoma suppressing the malignant growth of melanoma.
Asunto(s)
Carcinoma/patología , Melanoma Experimental/patología , Neoplasias Primarias Múltiples/patología , Enfermedades de Inmunodeficiencia Primaria/patología , Neoplasias Urológicas/patología , Animales , Carcinoma/inmunología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Femenino , Inyecciones Subcutáneas , Melanoma Experimental/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Neoplasias Primarias Múltiples/inmunología , Enfermedades de Inmunodeficiencia Primaria/inmunología , Ratas , Factores de Tiempo , Carga Tumoral , Neoplasias Urológicas/inmunologíaRESUMEN
Tyrosinase-catalyzed l-tyrosine oxidation is a key step in melanogenesis, and intense melanin formation is often a problem in chemotherapies or food preservation. Here we report that methyl cinnamate one of the constituents characterized from mycelium and sporocarp of American matsutake mushroom Tricholoma magnivelare inhibits both enzymatic and cellular melanin formation. Methyl cinnamate inhibits mushroom tyrosinase-catalyzed l-tyrosine oxidation while the oxidation of l-3,4-dihydroxyphenylalanine (l-DOPA) was not inhibited. In subsequent cellular assays, methyl cinnamate significantly suppressed melanogenesis of murine B16-F10 melanoma cells without affecting cell growth. However, methyl 3-phenylpropionate, a dihydro-derivative of methyl cinnamate, did not possess melanogenesis, indicating that the double bond in the enone moiety is a key Michael reaction acceptor to elicit the activity. In addition, a rather rare chlorinated benzaldehyde derivative, 3,5-dichloro-4-methoxybenzaldehyde isolated from the same source, was found to show potent cytotoxicity, and the chlorine atom reduced a tyrosinase inhibitory activity but enhanced cytotoxicity. Our findings suggest that methyl cinnamate is a novel melanogenesis inhibitor from natural sources.