RESUMEN
Citosol (thiamylal sodium) is one of generally used anesthetic-sedative agents for clinical patients, and it has not been reported to show induction of cytotoxic effects in cancer cells, especially in mice leukemia RAW 264.7 cells in vitro. In the present study, we investigated the cytotoxic effects of citosol on mice leukemic RAW 264.7 cells, including the effects on protein and gene expression levels which are determined by Western blotting and DNA microarray methods, respectively. Results indicated that citosol induced cell morphological changes, cytotoxic effect, and induction of apoptosis in RAW 264.7 cells. Western blotting analysis demonstrated that citosol promoted the levels of Fas, cytochrome c, caspase 9 and 3 active form and Bax levels, but it suppressed Bcl-xl protein level that may lead to apoptotic death in RAW 264.7 cells. Furthermore, DNA microarray assay indicated that citosol significantly promoted the expression of 5 genes (Gm4884, Gm10883, Lce1c, Lrg1, and LOC100045878) and significantly inhibited the expression of 24 genes (Gm10679, Zfp617, LOC621831, Gm5929, Snord116, Gm3994, LOC380994, Gm5592, LOC380994, LOC280487, Gm4638, Tex24, A530064D06Rik, BC094916, EG668725, Gm189, Hist2h3c2, Gm8020, Snord115, Gm3079, Olfr198, Tdh, Snord115, and Olfr1249). Based on these observations, citosol induced cell apoptosis and influenced gene expression in mice leukemia RAW 264.7 cells in vitro.
Asunto(s)
Apoptosis/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Hipnóticos y Sedantes/toxicidad , Tiamilal/toxicidad , Animales , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Perfilación de la Expresión Génica , Ratones , Análisis de Secuencia por Matrices de OligonucleótidosRESUMEN
Safrole, a component of piper betle inflorescence, is a documented rodent hepatocarcinogen and inhibits bactericidal activity and the release of superoxide anion (O(2-)) by polymorphonuclear leukocytes (PMNs). In the present study, we investigated the effects of safrole on immune responses, including natural killer (NK) cell cytotoxicity, phagocytic activity and population distribution of leukocytes from normal BALB/c mice. The cells population (cell surface markers) and phagocytosis by macrophages and monocytes from the peripheral blood mononuclear cells (PBMCs) were determined, and NK cell cytotoxicity from splenocytes of mice after oral treatment with safrole was performed using flow cytometric assay. Results indicated that safrole did not affect the weights of body, spleen and liver when compared with the normal mice group. Safrole also promoted the levels of CD11b (monocytes) and Mac-3 (macrophages) that might be the reason for promoting the activity of phagocytosis. However, safrole reduced the cell population such as CD3 (T cells) and CD19 (B cells) of safrole-treated normal mice by oral administration. Furthermore, safrole elevated the uptake of Escherichia coli-labelled fluorescein isothiocyanate (FITC) by macrophages from blood and significantly stimulated the NK cell cytotoxicity in normal mice in vivo. In conclusions, alterations of the cell population (the increase in monocytes and macrophages, respectively) in safrole-treated normal BALB/c mice might indirectly influence the immune responses in vivo.
Asunto(s)
Antígenos de Diferenciación/inmunología , Macrófagos/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Safrol/toxicidad , Animales , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Monocitos/efectos de los fármacos , Monocitos/inmunología , Bazo/efectos de los fármacos , Bazo/inmunología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunologíaRESUMEN
Capsaicin, a pungent compound found in hot chili peppers, has been reported to have antitumor activities in many human cancer cell lines, but the induction of precise apoptosis signaling pathway in human nasopharyngeal carcinoma (NPC) cells is unclear. Here, we investigated the molecular mechanisms of capsaicin-induced apoptosis in human NPC, NPC-TW 039, cells. Effects of capsaicin involved endoplasmic reticulum (ER) stress, caspase-3 activation and mitochondrial depolarization. Capsaicin-induced cytotoxic effects (cell death) through G0/G1 phase arrest and induction of apoptosis of NPC-TW 039 cells in a dose-dependent manner. Capsaicin treatment triggered ER stress by promoting the production of reactive oxygen species (ROS), increasing levels of inositol-requiring 1 enzyme (IRE1), growth arrest and DNA-damage-inducible 153 (GADD153) and glucose-regulated protein 78 (GRP78). Other effects included an increase in cytosolic Ca(2+), loss of the mitochondrial transmembrane potential (ΔΨ(m)), releases of cytochrome c and apoptosis-inducing factor (AIF), and activation of caspase-9 and -3. Furthermore, capsaicin induced increases in the ratio of Bax/Bcl-2 and abundance of apoptosis-related protein levels. These results suggest that ER stress- and mitochondria-mediated cell death is involved in capsaicin-induced apoptosis in NPC-TW 039 cells.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Capsaicina/farmacología , Calcio/metabolismo , Carcinoma , Caspasas/metabolismo , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Daño del ADN , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/fisiología , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/fisiopatología , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Canales Catiónicos TRPV/genéticaRESUMEN
The aim of this study was to investigate factors influencing career choices in radiology trainees. We distributed a 27-question written survey to all radiology registrars in Queensland. The questions investigated whether radiology was their first specialty choice, career satisfaction, ideal working conditions and attitudes regarding having children during the time of training. Forty-four of 51 surveys were returned (86% participation rate, 73% men, P = 0.048055) with 100% reporting a high job satisfaction; 28% of male registrars compared to 8% of female registrars did extra work outside of training to earn extra money (P = 0.000003), and 17% of female registrars took a leave of absence during their training, while no male registrar did (P = 0.087923). Only one female trainee worked part-time (P = 0.272727). In addition, 58% of female registrars planned a pregnancy (P = 0.731789) before completion of training; 83% of women versus 75% of men had no children (P = 0.329263). Only 5% of trainees agreed that it was easy to arrange part-time training, only 14% stated that it was easy to negotiate flexible work schedules and 7% agreed that it was easy to return to work after a period of absence. 'Time spent with immediate family' was rated the most important lifestyle factor, followed by 'work hours' and 'on-call duty'. The least important factors were 'being away from extended family', 'availability of part-time work' and whether 'work was in a rural location'. Overall job satisfaction is high among radiology trainees. Nevertheless, lifestyle factors, particularly those related to work time, are becoming more important for career decisions. This should be taken into account when designing and structuring radiology training to ensure that it is considered an attractive career choice.