RESUMEN
The aim of this study was to evaluate the in vitro and in vivo effects of the new chemotherapy agent Casiopeina III-ia [(4,4'-dimethyl-2,2'-bipiridine)(acetylacetonate) Copper (II) nitrate] on HCT-15 (p53-/-) colon cellular line. In vitro, the drug reduced the viability and induced necrosis and apoptosis in a dose dependent manner, without affecting cell cycle phases. Apoptosis was related to Bax increasing levels, suggesting a caspase-dependent mechanism of death, as verified by nucleosomal fragmentation of DNA. In vivo, the antitumor activity of Casiopeina III-ia was tested in HCT-15 cells transplanted to nude mice. In this study we will show that the novel antineoplastic agent Casiopeina III-ia is active on this colon tumor line, setting out as a good candidate for the treatment of colon tumors refractory to chemotherapy.
Asunto(s)
Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Neoplasias del Colon/prevención & control , Compuestos Organometálicos/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Western Blotting , Peso Corporal/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Ratones , Ratones Desnudos , Compuestos Organometálicos/química , Proteína X Asociada a bcl-2/metabolismoRESUMEN
OBJECTIVES: There is growing evidence of the relationship between sleep and the immune response. Studies aimed at elucidating the function of rapid eye movement (REM) sleep have found it difficult to separate the effects due to REM sleep deprivation and the effects due to the stress produced by the deprivation procedure. It has been claimed that immobilization is the main stressor that the animals have to face during the deprivation process. In this study, we analyzed the effects of short-term (24 h) and long-term (240 h) REM sleep deprivation on the distribution of lymphocyte subsets in the peripheral blood of rats. In addition, these effects were compared with those obtained after both short- and long-term stress by immobilization. METHODS: Lymphocyte population bearing surface markers such as CD5 (T cells), CD45RA (B cells), CD4 (T helper/inducer cells), CD8 (T suppressor/cytotoxic cells) and CD161 (NK cells) were analyzed using monoclonal antibodies. Lymphocyte subsets were assessed by flow cytometry. RESULTS: Both short- and long-term REM sleep deprivation decreased the percentage of T lymphocytes and induced a significant increase in NK cells. Short-term immobilization induced only a significant increase in the percentage of B lymphocytes and a decrease in the percentage of T lymphocytes, while long-term immobilization did not elicit any change. CONCLUSION: The present results support the notion that REM sleep deprivation and immobilization stress each exert particular effects on the immune system. These data suggest that the characteristics of the immune response will depend on the nature of the behavioral manipulation.