RESUMO
Epigallocatechin gallate (EGCG), which is derived from green tea, is well known for its chemopreventive activity. Several studies have shown that p53 plays an important role in the activity of EGCG; however, the mechanism by which EGCG regulates p53 requires further investigation. In the present study, we showed that EGCG inhibits anchorage-independent growth of human lung cancer cells by upregulating p53 expression. EGCG treatment can substantially increase p53 stability, promote nuclear localization of p53 and decrease nuclear accumulation of MDM2. We also found that EGCG increases the phosphorylation of p53 at Ser15 and Ser20 and enhances its transcriptional activity. Although EGCG promotes MDM2 expression in a p53-dependent manner, the interaction between MDM2 and p53 was significantly inhibited following EGCG treatment, which resulted in the inhibition of MDM2-mediated p53 ubiquitination. Thus, our results suggest that the stabilization and activation of p53 may partly contribute to the anticancer activity of EGCG.
Assuntos
Catequina/análogos & derivados , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Proteína Supressora de Tumor p53/metabolismo , Ubiquitinação/efeitos dos fármacos , Catequina/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/genética , Núcleo Celular/metabolismo , Células HEK293 , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Fosforilação/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Chá/metabolismo , Transcrição Gênica/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Regulação para Cima/efeitos dos fármacosRESUMO
Two Gram-negative, non-motile, rod-shaped strains, BQ4-1(T) and NHI3-2, isolated respectively from the healthy and diseased part of Populus ×euramericana canker bark, were characterized using a polyphasic approach. Chemotaxonomic characterization supported the inclusion of the two strains in the genus Acinetobacter, with genomic DNA G+C contents (42.5-43 mol%) within the range observed for this genus (38-47 mol%) and 9-octadecenoic acid (C18 : 1ω9c, 39.87 %), hexadecanoic acid (C16 : 0, 11.26 %) and summed feature 3 (comprising C16 : 1ω7c/C16 : 1ω6c, 18.90 %) as major fatty acids. Phylogenetic analysis based on 16S rRNA, rpoB and gyrB gene sequences revealed that strains BQ4-1(T) and NHI3 did not cluster with any species with validly published names, and formed a distinct cluster with 99-100 % bootstrap support on three phylogenetic trees within the genus Acinetobacter. Acid was not produced from d-glucose, and haemolysis was not observed on agar media supplemented with sheep erythrocytes. On the basis of phenotypic, genotypic and phylogenetic characteristics, the two strains are considered to represent a novel species of the genus Acinetobacter, for which the name Acinetobacter puyangensis sp. nov. is proposed. The type strain is BQ4-1(T) (= CFCC 10780(T) = JCM 18011(T)).