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1.
Cancer Sci ; 95(8): 666-73, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15298730

RESUMO

Recent studies have shown that selective cyclooxygenase-2 (COX-2) inhibitors induce growth inhibition and cell cycle arrest in hepatocellular carcinoma (HCC) cell lines. However, the mechanism by which COX-2 inhibitors regulate the cell cycle and whether or not growth signal pathways are involved in the growth inhibition remain unclear. In this study, we investigated the mechanisms of growth inhibition and cell cycle arrest by etodolac, a selective COX-2 inhibitor, in HCC cell lines, HepG2 and PLC/PRF/5, by studying cell cycle regulatory proteins, and the MAP kinase and PDK1-PKB/AKT signaling pathways. Etodolac inhibited growth and PCNA expression and induced cell cycle arrest in both HCC cell lines. Etodolac induced p21WAF1/Cip1 and p27Kip1 expression and inhibited CDK2, CDK4, CDC2, cyclin A and cyclin B1 expression, but did not affect cyclin D1 or cyclin E. HGF and 10% FBS induced ERK phosphorylation, but phosphorylation of p38, JNK and AKT was down-regulated by etodolac. PD98059, a selective inhibitor of ERK phosphorylation, induced growth inhibition, the expression of p27Kip1 and cell cycle arrest. In conclusion, p21WAF1/Cip1, p27Kip1, CDK2, CDK4, CDC2, cyclin A, cyclin B1 and the MAP kinase signaling pathway are involved in growth inhibition and cell cycle arrest by a selective COX-2 inhibitor in HCC cell lines.


Assuntos
Carcinoma Hepatocelular/patologia , Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Quinases Ciclina-Dependentes/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Etodolac/farmacologia , Neoplasias Hepáticas/patologia , Proteínas Quinases Ativadas por Mitógeno/farmacologia , Proteínas de Ciclo Celular , Fatores de Troca do Nucleotídeo Guanina , Humanos , Proteínas Nucleares , Células Tumorais Cultivadas
2.
Ann Nutr Metab ; 47(3-4): 165-9, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12743469

RESUMO

BACKGROUND: Pipecolic acid, a metabolite of lysine, is found in human physiological fluids and is thought to play an important role in the central inhibitory gamma-aminobutyric acid system. However, it is unclear whether plasma D- and L-pipecolic acid originate from oral food intake or intestinal bacterial metabolites. METHODS: We analyzed the contents of D- and L-pipecolic acid in several processed foods including dairy products (cow's milk, cheese and yogurt), fermented beverages (beer and wine) and heated samples (beef, bovine liver, bread and tofu) to clarify the relationship between plasma D- and L-pipecolic acid and dietary foods. RESULTS: Our study revealed that some of the samples contained high concentrations of total pipecolic acid, and a higher proportion of L- than D-isomers. The other samples also showed high proportions of L-pipecolic acid. It was also shown that there is no significant change in the ratio of the D-isomer before and after heat treatment. The heat treatments could not cause the racemization of pipecolic acid in this study. CONCLUSION: These findings suggest that plasma pipecolic acid, particularly the D-isomer, does not originate from direct food intake and that D- and L-pipecolic acid can possibly be derived from intestinal bacterial metabolites.


Assuntos
Análise de Alimentos , Ácidos Pipecólicos/análise , Bebidas Alcoólicas/análise , Animais , Pão/análise , Bovinos , Cromatografia Líquida de Alta Pressão , Laticínios/análise , Temperatura Alta , Carne/análise , Verduras/química
3.
J Agric Food Chem ; 50(11): 3346-50, 2002 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-12010009

RESUMO

The effects of a canned mixed green vegetable and fruit beverage, containing broccoli (Brassica oleracea L. var. botrytis L.) and cabbage (Brassica oleracea L. var. capitata L.) as main materials, on serum lipid levels in hypercholesterolemic patients were investigated. Thirty-one adult subjects were administered two cans of the beverage (160 g/can) per day for 3 weeks. Their serum total cholesterol (TC) levels significantly decreased from 6.7 +/- 0.8 to 6.1 +/- 0.6 mmol/L, and, more strikingly, the level of low-density lipoprotein cholesterol (LDL-C) significantly decreased from 4.4 +/- 0.8 to 3.8 +/- 0.7 mmol/L. At 9 weeks after the cessation of the administration, these levels had returned to the preadministration levels. Furthermore, 14 other subjects who were administered one can of the sample for 12 weeks also showed a significant reduction in the levels of serum TC and LDL-C. Thus, daily consumption of this mixed green vegetable and fruit beverage may be useful in lowering serum TC and LDL-C levels in hypercholesterolemic patients.


Assuntos
Bebidas , LDL-Colesterol/sangue , Frutas , Hipercolesterolemia/sangue , Verduras , Adulto , Índice de Massa Corporal , Peso Corporal , Brassica , Colesterol/sangue , Feminino , Humanos , Hipercolesterolemia/dietoterapia , Masculino , Pessoa de Meia-Idade
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