Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas de Membrana/metabolismo , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Humanos , Neoplasias Hepáticas/patologia , RNA Mensageiro/genéticaRESUMO
Salvia plebeia R. Br is a traditional Chinese herb which has been considered as an inflammatory mediator used for treatment of many infectious diseases including hepatitis. Previously, the compound homoplantaginin was isolated in our group. Hence, we evaluated the protective effects of homoplantaginin on hepatocyte injury. Homoplantaginin displayed an antioxidant property in a cell-free system and showed IC(50) of reduction level of DPPH radical at 0.35 microg/ml. In human hepatocyte HL-7702 cells exposed to H(2)O(2), the addition of 0.1-100 microg/ml of homoplantaginin, which did not have a toxic effect on cell viability, significantly reduced lactate dehydrogenase (LDH) leakage, and increased glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in supernatant. In vivo assay, we employed the model of Bacillus Calmette-Guérin (BCG)/lipopolysaccharide (LPS)-induced hepatic injury mice to evaluate efficacy of homoplantaginin. Homoplantaginin (25-100mg/kg) significantly reduced the increase in serum alanine aminotranseferase (ALT) and aspartate aminotransferase (AST), decreased the levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1). The same treatment also reduced the content of thiobarbituric acid-reactive substances (TBARS), elevated the levels of GSH, GSH-Px and SOD in hepatic homogenate. The histopathological analysis showed that the grade of liver injury was ameliorated with reduction of inflammatory cells and necrosis of liver cells in homoplantaginin treatment mice. These results suggest that homoplantaginin has a protective and therapeutic effect on hepatocyte injury, which might be associated with its antioxidant properties.
Assuntos
Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Flavonoides/farmacologia , Glucosídeos/farmacologia , Hepatócitos/efeitos dos fármacos , Substâncias Protetoras , Salvia/química , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Enzimas/sangue , Hepatócitos/patologia , Humanos , Peróxido de Hidrogênio/toxicidade , Interleucina-1/biossíntese , L-Lactato Desidrogenase/metabolismo , Fígado/patologia , Testes de Função Hepática , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fator de Necrose Tumoral alfa/biossínteseRESUMO
BACKGROUND: Sialic acid, as a terminal saccharide residue on cell surface glycoconjugates, plays an important role in a variety of biological processes. However, the precise nature of the molecules in gastric cancers has not been unveiled nor documented to be of clinical relevance. Herein, we measured the expression of alpha 2, 3-linked sialic acid residues by using a specific lectin as well as the potential of invasion and metastasis of gastric cancer was analyzed. METHODS: The expression of alpha 2, 3-linked sialic acid residues in 100 cases of gastric cancer samples was evaluated using Maackia amurensis leukoagglutinin (MAL) histochemical staining analysis. The assays of cytochemical staining and flow cytometry were employed to determine the MAL positive cells in the gastric cancer cell lines. The activities of invasion and migration were evaluated using the assays of cell adhesion and transwell chamber. RESULTS: The staining of MAL in gastric cancer tissues showed that high levels of alpha 2, 3-linked sialic acid residues were closely associated with the invasive depth (P=0.0003) and lymph node metastasis (P=0.0441). In gastric adenocarcinoma cell lines, SGC-7901, the highly metastatic cell line, displayed the most positive reaction with MAL among the selected cell lines. The potential of invasion and migration was confirmed using the assays of adhesion and transwell chamber that SGC-7901 exhibited the high activity of adhesion to extracellular matrix (ECM) and penetration to Matrigel. CONCLUSION: These results suggested that high level of alpha 2, 3-linked sialic acid residues was associated with metastatic potential of gastric cancer cells.
Assuntos
Ácido N-Acetilneuramínico/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Adesão Celular , Linhagem Celular Tumoral , Ensaios de Migração Celular , Movimento Celular , Feminino , Glicoconjugados , Humanos , Maackia , Masculino , Pessoa de Meia-Idade , Ácido N-Acetilneuramínico/química , Invasividade Neoplásica , Metástase Neoplásica , Fito-Hemaglutininas , Lectinas de PlantasRESUMO
A new saponin, gypoldoside A (1), was isolated from the roots of Gypsophila oldhamiana. On the basis of in-depth NMR-spectroscopic and mass-spectrometric analysis, in combination with chemical evidence, its structure was established as 3-O-{beta-D-galactopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->3)]-beta-D-glucuronopyranosyl}quillaic acid 28-[alpha-L-arabinopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-fucopyranosyl] ester. Compound 1 was found to be highly active against three different human cancer cell lines, with IC50 values in the low micromolar range.
Assuntos
Antineoplásicos/farmacologia , Caryophyllaceae/química , Raízes de Plantas/química , Saponinas/farmacologia , Linhagem Celular Tumoral , Humanos , Concentração Inibidora 50RESUMO
Curcumin, one of the major components of tumeric, the dried rhizome of Curcuma longa L, has been shown to have anti-proliferating and anti-carcinogenic properties. In this study, we examined the effects of curcumin on cell growth and telomerase activity in human cancer cell lines Bel7402, HL60 and SGC7901. Curcumin (1-32 microM) showed anti-proliferating effects on these cell lines in a dose-dependent manner in vitro, and anti-tumor effects when curcumin (50-200 mg/kg) was orally administered to nude mice transplanted with the cancer cells. When the cells were treated with 1 microM of curcumin for 120 h, apoptotic cells were observed by means of the adridine orange/ethidium bromide staining method, single cell microgel electrophoresis and flow cytometric analysis. On the other hand, suppression of telomerase activity in extracts of the cells treated with 1 microM of curcumin was observed by means of a telomeric repeat amplification protocol - silver staining assay. These results suggest that curcumin could suppress telomerase activity in the cancer cell lines and that the decrease of telomerase expression followed by induction of apoptosis might be involved in the anti-proliferating effect of curcumin.