RESUMO
ß-Escin, a natural triterpene saponin was extracted from Aesculus hippocastanum seeds, which have been widely used to treat inflammation in traditional medicine. In an effort to study the possible anti-tumor effects of ß-escin, we performed wound healing, invasion, and adhesion assays to examine the effects of ß-escin on cell migration, invasion, and angiogenesis. Our results revealed that ß-escin inhibits cell migration as well as motility in B16F10 and SK-MEL5 cells in a dose-dependent manner. RT-PCR and Western blot analysis showed that ß-escin increased TIMP-1, -2 while significantly downregulated phosphorylated extracellular signal-regulated kinase (p-ERK) expression, and suppressing nuclear factor-kappa B (NF-κB) and inhibitor of nuclear factor-kappa B (IκB) expression. Overall, the data from the current study suggest that ß-escin has the potential for inhibiting both metastatic and angiogenic activities, and are the earliest evidence for the involvement of the NF-κB/IκB signaling in ß-escin-induced anti-tumor effects.
Assuntos
Aesculus/química , Escina/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Sistema de Sinalização das MAP Quinases , Melanoma/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Escina/uso terapêutico , Humanos , Proteínas I-kappa B/metabolismo , Melanoma/tratamento farmacológico , Camundongos , Fosforilação , Fitoterapia , Extratos Vegetais/uso terapêutico , Sementes , Transdução de SinaisRESUMO
In this study, Co/Al203 catalyst for Fischer-Tropsch synthesis was prepared via slurry impregnation method and the catalyst was characterized by various techniques such as TPR, XRD, TGA and N2 physisorption. To dissolve the wax, after-reaction catalyst was dewaxed using n-Hexane at 60 *C. The experiments were performed in a bench-scale fixed-bed reactor, under the reaction condition of 230 degrees C, 20 bar and feed volume ratio of H2:CO:N2 = 2:1:0.5-1.5. The methane selectivity and the ratio of olefin to paraffin among C2-C4 hydrocarbons were increased with higher contents of nitrogen in feed gas which result in higher partial pressure ratio of H2 to CO, and also affect methane selectivity which has a significant role in increased CO conversion.
Assuntos
Óxido de Alumínio/química , Cálcio/química , Nitrogênio/química , Monóxido de Carbono/química , Catálise , Hexanos/química , Hidrogênio/químicaRESUMO
OBJECTIVE: Nuclear factor-kappaB (NF-kappaB) has been implicated as a therapeutic target for the treatment of rheumatoid arthritis (RA). The purpose of this study was to determine whether A20, a universal inhibitor of NF-kappaB, might have antiarthritic effects. METHODS: An adenovirus containing A20 complementary DNA (AdA20) was used to deliver A20 to human rheumatoid fibroblast-like synoviocytes (FLS) in vitro as well as to mice with collagen-induced arthritis (CIA) in vivo via intraarticular injection into the ankle joints bilaterally. RESULTS: In vitro experiments demonstrated that AdA20 suppressed NF-kappaB activation, chemokine production, and matrix metalloproteinase secretion induced by tumor necrosis factor alpha in FLS. Mice with CIA that were treated with AdA20 had a lower cumulative disease incidence and severity of arthritis, based on hind paw thickness, radiologic and histopathologic findings, and inflammatory cytokine levels, than did control virus-injected mice. The protective effects of AdA20 were mediated by the inhibition of the NF-kappaB signaling pathway. The severity of arthritis was also significantly decreased in the untreated front paws, indicating a beneficial systemic effect of local suppression of NF-kappaB. Surprisingly, mice treated with AdA20 after the onset of CIA had significantly decreased arthritis severity from the onset of clinical signs to the end of the study. CONCLUSION: These results suggest that using A20 to block the NF-kappaB pathway in rheumatoid joints reduces both the inflammatory response and the tissue destruction. The development of an immunoregulatory strategy based on A20 may therefore have therapeutic potential in the treatment of RA.
Assuntos
Artrite Experimental/tratamento farmacológico , Osso e Ossos/efeitos dos fármacos , Inflamação/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Nucleares/metabolismo , Membrana Sinovial/efeitos dos fármacos , Análise de Variância , Animais , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Western Blotting , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Proteínas de Ligação a DNA , Ensaio de Desvio de Mobilidade Eletroforética , Humanos , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos DBA , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Proteína 3 Induzida por Fator de Necrose Tumoral alfaRESUMO
BACKGROUND: Oxidative stress and inflammation are implicated in the pathogenesis of cisplatin-induced nephrotoxicity. l-2-oxothiazolidine-4-carboxylic acid (OTC) is a cysteine prodrug, and increases cellular glutathione (GSH). OTC is converted to cysteine by the intracellular enzyme, oxoprolinase. To date, the protective role of OTC on cisplatin-induced renal injury has not been investigated. The purpose of the present study was to examine the protective effect of OTC on cisplatin-induced renal injury and to examine the mechanism of its protection. METHODS: Mice were treated with cisplatin with or without administration of OTC. The generation of reactive oxygen species (ROS), expression of intercellular adhesion molecule (ICAM)-1 and monocyte chemoattractant protein (MCP)-1 were determined in the kidney using 2',7'-dichlorofluorescein diacetate, immunostaining or western blot analysis. Nuclear factor (NF)-kappaB activity, infiltration of F4/80-positive cells and apoptosis were also investigated in addition to renal function and histology using electrophoretic mobility shift assay, immunostaining, western blot analysis, uridine triphosphate (dUTP) nick-end labelling or periodic acid-Schiff staining. The effect of OTC on superoxide dismutase activity and GSH level in cisplatin-treated normal adult human kidney (HK-2) cells were measured using assay kits. RESULTS: The administration of OTC resulted in a significant reduction of cisplatin-induced ROS production, the p65 subunit of NF-kappaB translocation into nucleus, expression of ICAM-1, caspase 3 activity, expression of MCP-1 and the infiltration of macrophages into renal tissue. OTC markedly ameliorated renal damage induced by cisplatin through antioxidant and anti-inflammatory effect. CONCLUSIONS: These results suggest that OTC can be a potential therapeutic agent in cisplatin-induced renal injury through decreasing the ROS levels and activation of NF-kappaB.