RESUMEN
Human breast cancer cell line Hs578T was stably transfected with cDNA for cyclooxygenase-1 or -2. When the cells overexpressing cyclooxygenase-1 or -2 were stimulated with concanavalin A, the processing of matrix metalloproteinase-2 was observed with the aid of gelatin zymography. This processing was not seen in mock-transfected and original cells which did not express detectable cyclooxygenase activity. Furthermore, Northern blotting showed 8-13 fold induction of membrane-type 1 matrix metalloproteinase which processed matrix metalloproteinase-2 in the cells expressing cyclooxygenases. These findings suggest that both isoforms of cyclooxygenase mediate the processing of matrix metalloproteinase-2 through induction of membrane-type I metalloproteinase in breast cancer cells.
Asunto(s)
Isoenzimas/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Prostaglandina-Endoperóxido Sintasas/genética , Neoplasias de la Mama , Concanavalina A/farmacología , Ciclooxigenasa 1 , Ciclooxigenasa 2 , ADN Complementario , Activación Enzimática , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/genética , Proteínas de la Membrana , Mutación , ARN Mensajero/metabolismo , Transfección , Células Tumorales CultivadasAsunto(s)
Metaloendopeptidasas/antagonistas & inhibidores , Inhibidores de Proteasas/farmacología , Evaluación Preclínica de Medicamentos/métodos , Gelatinasas/antagonistas & inhibidores , Cinética , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 7 de la Matriz , Metaloproteinasas de la Matriz Asociadas a la Membrana , Proteínas Recombinantes/antagonistas & inhibidores , TéRESUMEN
The antiulcer activities of 59 methanol and aqueous extracts obtained from 59 crude drugs on the ethanol-HCl-induced ulceration in rats were investigated. Among them 15 extracts were selected and they were further examined for their effects on indomethacin-, aspirin- and the water-immersion stress-induced ulcer. From these results, the methanol extract of root of Iris germanica was found to, show potent antiulcer activities. The above methanol extract was separated into 3 portions by solvent extraction, and the ether soluble portion was fractionated into 5 fractions (1 to 5) by chromatography. Fractions 4 and 5 showed significant antiulcer activities. Fraction 4 was further purified and the obtained gamma-irigermanal exhibited a potent antiulcer activity. However, further investigations are required to understand the mechanism.