RESUMEN
Natural silicate materials, including zeolite clinoptilolite, have been shown to exhibit diverse biological activities and have been used successfully as a vaccine adjuvant and for the treatment of diarrhea. We report a novel use of finely ground clinoptilolite as a potential adjuvant in anticancer therapy. Clinoptilolite treatment of mice and dogs suffering from a variety of tumor types led to improvement in the overall health status, prolongation of life-span, and decrease in tumors size. Local application of clinoptilolite to skin cancers of dogs effectively reduced tumor formation and growth. In addition, toxicology studies on mice and rats demonstrated that the treatment does not have negative effects. In vitro tissue culture studies showed that finely ground clinoptilolite inhibits protein kinase B (c-Akt), induces expression of p21WAF1/CIP1 and p27KIP1 tumor suppressor proteins, and blocks cell growth in several cancer cell lines. These data indicate that clinoptilolite treatment might affect cancer growth by attenuating survival signals and inducing tumor suppressor genes in treated cells.
Asunto(s)
Adyuvantes Farmacéuticos/uso terapéutico , Neoplasias/tratamiento farmacológico , Proteínas Serina-Treonina Quinasas , Zeolitas/uso terapéutico , Adyuvantes Farmacéuticos/efectos adversos , Adyuvantes Farmacéuticos/farmacología , Envejecimiento/fisiología , Animales , Apoptosis/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Proteínas de Ciclo Celular/análisis , División Celular/efectos de los fármacos , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Ciclinas/análisis , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/patología , Perros , Femenino , Células HeLa , Humanos , Masculino , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/patología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Neoplasias/patología , Neoplasias/veterinaria , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Células Tumorales Cultivadas , Proteínas Supresoras de Tumor/análisis , Zeolitas/efectos adversos , Zeolitas/farmacologíaRESUMEN
Young cats (Felis domestica), aged 10-13 weeks, were intermittently exposed to a temperature of -30 degrees C for two periods of 1 hr per day. Animals were sacrificed on the 7th day and adipose tissue from the perirenal, pericardial, axillary, interscapular, and subcutaneous-inguinal depots was examined by electron microscopy and analysed stereologically. All examined depots were morphologically changed after cold treatment. Adipose tissue of perirenal, pericardial, and axillary depots showed a greater decrease in lipid content than the interscapular and subcutaneous-inguinal depots, but other changes were similar. Compared to the control group, which consisted of typical white adipose tissue, the diameter of adipose cells examined after cold treatment was diminished, in extreme cases to 18 micron (from 75 micron in the control group). The number of capillaries per cell was doubled (as evaluated on semithin sections). The most dramatic changes were observed in the mitochondria. Their volume increased to 0.48 micron 3 (from 0.13 micron 3 in the control), and the surface density of mitochondrial cristae per mitochondrial volume increased to 50 micron 2/micron 3 (from 32 in the control). Pleomorphism in mitochondrial size and inner structure and the presence of intramitochondrial electron-dense bodies and crystalline structures led us to conclude that the cold stress induced an increase in the absolute number of mitochondria in the adipose cells. The adipose tissue after cold treatment thus morphologically resembled the brown adipose tissue of cold-acclimated rodents. This implies that the adipose tissue of young cats can change its morphology and function, depending on the requirements of the organism.