RESUMEN
Brazilein, a bioactive compound isolated from Caesalpinia sappan L., has long been used in oriental folk medicines. Cancer metastasis is a primary cause of cancer death. However, the anti-metastatic effects of brazilein remain elusive. In this study, we found that brazilein inhibited human breast cancer MDA-MB-231 cell migration and invasion using wound-healing assay and Boyden chamber assay. The results of Western blot, gelatin zymography and reversed transcription-PCR analysis showed that brazilein suppressed matrix metalloproteinase-2 (MMP-2) expression in a concentration-dependent manner. Brazilein also decreased the nuclear protein level of nuclear factor kappaB (NF-κB). Brazilein potently suppressed the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), phosphatidylinositide-3-kinase (PI3K) and Akt, but did not affect phosphorylation of extracellular signal regulating kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK). Additionally, treatment of SB203580 (p38 MAPK inhibitor) or wortmannin (PI3K inhibitor) resulted in a reduced activity and expression of MMP-2 as well as inhibition on cell migration and invasion in MDA-MB-231 cells. Taken together, these results suggest that brazilein inhibition of MDA-MB-231 cells may be mediated through inactivation of both PI3K/Akt and p38 MAPK signaling pathways, leading to inhibitory effect on NF-κB activation. Consequently, brazilein suppresses MMP-2 expression, and thus confers anti-migration and anti-invasion of MDA-MB-231 cells.
Asunto(s)
Antineoplásicos/farmacología , Benzopiranos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Indenos/farmacología , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Western Blotting , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Femenino , Humanos , Estructura Molecular , FN-kappa B/química , FN-kappa B/metabolismo , Reacción en Cadena de la PolimerasaRESUMEN
The first total synthesis of the naturally occurring tetracyclic homoisoflavonoid brazilein (1) and 14 new analogs (1a-n) is reported. Target compounds and intermediates were assayed for anti-inflammatory effects on superoxide anion generation and elastase release by human neutrophils in response to fMLP/CB, and for cytotoxic activity against nasopharyngeal (KB), vincristine-resistant nasopharyngeal (KBvin), lung (A549) and prostate (DU-145) human cancer cell lines. The most active compound 1b showed potent effects on superoxide anion generation and elastase release with IC(50) values of 1.2 and 1.9 microM, respectively, and was 65 times more potent than phenylmethylsulfonyl fluoride (PMSF), the positive control, in the latter assay. Additionally, 1b exhibited broad spectrum in vitro anticancer activity with IC(50) values of 6-11 microM against the four tested cancer cell lines.
Asunto(s)
Antiinflamatorios no Esteroideos/síntesis química , Antineoplásicos/síntesis química , Benzopiranos , Citotoxinas/síntesis química , Indenos , Antiinflamatorios no Esteroideos/aislamiento & purificación , Antiinflamatorios no Esteroideos/farmacología , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Línea Celular Tumoral , Citotoxinas/aislamiento & purificación , Citotoxinas/farmacología , Evaluación Preclínica de Medicamentos/métodos , Medicamentos Herbarios Chinos/síntesis química , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Humanos , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunologíaRESUMEN
In a continuing study to isolate novel antitumor agents from rainforest plants, three new isopropenylfurano-beta-naphthoquinones, designated lantalucratins A (1), B (2), and C (3), and three new isoprenyl-alpha-naphthoquinones, designated lantalucratins D (4), E (5), and F (6), were isolated from Lantana involucrata. Their structures were determined on the basis of NMR and X-ray crystallographic analyses. Compounds 1 and 2 showed cytotoxic activities against various human tumor cell lines, including drug-resistant variants, with IC50 values of 1.0-4.9 microM.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Lantana/química , Naftoquinonas/aislamiento & purificación , Plantas Medicinales/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Naftoquinonas/química , Naftoquinonas/farmacología , Resonancia Magnética Nuclear Biomolecular , Puerto Rico , Células Tumorales CultivadasRESUMEN
El presente estudio in vitro midió la cantidad de fluoruro liberado por un ionómero- resina Fuji Ortho LC bajo los efectos de los vehículos de recarga (gel, enjuague bucal, pasta dental y barniz) durante un periodo de 21 días. Se prepararon 25 muestras en forma de placas rectangulares de 15 mm x 10 mm x 1 mm. Se sumergió cada placa en ml de agua deionizada y se mantuvo a 37°C durante todo el estudio. El agua deionizada fue renovada luego de cada medición. Previa estabilización de la solución con 5 ml del buffer Tisab III, se realizaron mediciones diariamente por los primeros 5 días y a los 10, 15 y 21 días del estudio, en mV con un electrodo selectivo de fluoruro acoplado a un analizador iónico. Se fluorizaron 5 muestras al inicio y cada cinco días con gel fluorado; otras 5 muestras con enjuague bucal; otras 5 con pasta dental; y otras 5 con barniz. Análisis estadísticos fueron hechos con las pruebas de Kruskall-Wallis, "r" de Pearson y Wilcoxon. Los resultados indican que todas las muestras presentaron la mayor cantidad acumulada de fluoruro liberado en el primer día que luego mostró una tendencia a disminuir, las muestras con gel y barniz liberaron la mayor y menor cantidad respectivamente. Se encontró que el efecto de recarga por parte de los vehículos hace que el material aumente su liberación de fluoruro en el momento de aplicación para posteriormente disminuirla.
Asunto(s)
Antisépticos Bucales , Cementos de Ionómero Vítreo , Cementos de Resina , Pastas de Dientes , Fluoruros , Geles , PinturaRESUMEN
Fractionation of the chloroform extract from the aerial part of Argemone mexicana led to the isolation of two benzophenanthridine-type alkaloids, N-demethyloxysanguinarine and pancorine; three benzylisoquinoline-type alkaloids, (+)-1,2,3,4-tetrahydro-1-(2-hydroxymethyl-3,4-dimethoxyphenylmethyl)-6,7-methylenedioxyisoquinoline, (+)-higenamine and (+)-reticuline. Among them, N-demethyloxysanguinarine is a new compound, and (+)-1,2,3,4-tetrahydro-1-(2-hydroxymethyl-3,4-dimethoxyphenylmethyl)-6,7-methylenedioxy-isoquinoline was isolated form a natural source for the first time, to which was assigned a trivial name, (+)-argenaxine. In addition, six known non-alkaloidal compounds were also isolated and identified. All compounds were characterized on the basis of their spectral data and chemical evidences. Some isolated alkaloids from this species were evaluated for their cytotoxicity to human nasopharyngeal carcinoma (HONE-1) and human gastric cancer (NUGC) cell lines. Chelerythrine was found to exhibit significant activity against NUGC cell line, while angoline inhibited both types. (+)-Argenaxine showed moderate activity against the NUGC cell line.
Asunto(s)
Alcaloides/toxicidad , Argemone/química , Supervivencia Celular/efectos de los fármacos , Isoquinolinas/toxicidad , Fenantridinas/aislamiento & purificación , Fenantridinas/toxicidad , Componentes Aéreos de las Plantas/química , Alcaloides/química , Alcaloides/aislamiento & purificación , Humanos , Isoquinolinas/química , Isoquinolinas/aislamiento & purificación , Modelos Moleculares , Estructura Molecular , Neoplasias Nasofaríngeas , Fenantridinas/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Neoplasias Gástricas , Células Tumorales CultivadasRESUMEN
Two new protopine-type alkaloids, argemexicaine A (1) and argemexicaine B (2), along with thirteen known alkaloids, were isolated from MeOH extracts of Formosan Argemone mexicana L. (Papaveraceae). Physical and spectral analyses, particularly IR and thermo-modulated 1D and 2D NMR, were used to determine the transannular conformations of the isolated protopine-type alkaloids. The known benzo[ c]phenanthridine (+/-)-6-acetonyldihydrochelerythrine (5) exhibited significant anti-HIV activity in H9 lymphocytes with EC50 and TI (Therapeutic Index) values of 1.77 microg/mL and 14.6, respectively.