RESUMO
Glioblastoma is a common central nervous system tumor and despite considerable advancements in treatment patient prognosis remains poor. Angiogenesis is a significant prognostic factor in glioblastoma, antiangiogenic treatments represent a promising therapeutic approach. Vascular endothelial growth factor A (VEGFA) is a predominant regulator of angiogenesis and mounting evidence suggests that the Wnt signaling pathway serves a significant role in tumor angiogenesis. As a positive regulator of the Wnt/ßcatenin signaling pathway, frequently rearranged in advanced Tcell lymphomas1 (FRAT1) is highly expressed in human glioblastoma and is significantly associated with glioblastoma growth, invasion and migration, as well as poor patient prognosis. Bioinformatics analysis demonstrated that both VEGFA and FRAT1 were highly expressed in most tumor tissues and associated with prognosis. However, whether and how FRAT1 is involved in angiogenesis remains to be elucidated. In the present study, the relationship between FRAT1 and VEGFA in angiogenesis was investigated using the human glioblastoma U251 cell line. Small interfering RNAs (siRNAs) were used to silence FRAT1 expression in U251 cells, and the mRNA and protein expression levels of VEGFA, as well as the concentration of VEGFA in U251 cell supernatants, were determined using reverse transcriptionquantitative PCR, western blotting and ELISA. A tube formation assay was conducted to assess angiogenesis. The results demonstrated that siRNA knockdown significantly decreased the protein expression levels of FRAT1 in U251 cells and markedly decreased the mRNA and protein expression levels of VEGFA. Furthermore, the concentration of VEGFA in the cell supernatant was significantly reduced and angiogenesis was suppressed. These results suggested that FRAT1 may promote VEGFA secretion and angiogenesis in human glioblastoma cells via the Wnt/ßcatenin signaling pathway, supporting the potential use of FRAT1 as a promising therapeutic target in human glioblastoma.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Encefálicas/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Neovascularização Patológica/genética , Proteínas Proto-Oncogênicas/genética , Fator A de Crescimento do Endotélio Vascular/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Western Blotting , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Células Cultivadas , Feminino , Glioblastoma/irrigação sanguínea , Glioblastoma/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas/metabolismo , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator A de Crescimento do Endotélio Vascular/metabolismo , Via de Sinalização Wnt/genética , beta Catenina/genética , beta Catenina/metabolismoRESUMO
A new flavone( 1) has been isolated from the whole plant of Cassia nomame by using various chromatographic techniques,including silica gel,Sephadex,MCI-gel resin,and RP-HPLC,and its structure was determined as 8,4'-dimethoxy-7-( 2-oxopropyl)-flavone based on spectroscopic data. The biological activity test showed that this compound displayed potent cytotoxicity against NB4,SH-SY5 Y,PC3,A549 and MCF-7 cell lines with IC50 values 2. 2,1. 8,3. 4,4. 5 and 1. 6 µmol·L-1,respectively.
Assuntos
Cassia , Flavonas , Senna , Cromatografia Líquida de Alta Pressão , Humanos , Células MCF-7RESUMO
A new isobenzofuranone derivative was isolated from Chaenomeles sinensis by using various chromatographic techniques,including silica gel,Sephadex LH-20,MCI-gel resin and RP-HPLC. This compound was determined as 2,2-dimethyl-5-( 2-oxopropyl)-2 H-furo[3,4-h]chromen-7( 9 H)-one( 1) by NMR,MS,IR and UV spectra,and was also evaluated for its antibacterial activity. The results showed that it showed prominent antibacterial activity with MIC90 value of( 53. 7±4. 5) mg·L-1 for methicillin resistant Staphylococcus aureus( MRSA) strain. This value is close to that of levofloxacin [with MIC90 value( 50. 2± 4. 2) mg·L-1].
Assuntos
Antibacterianos/farmacologia , Benzofuranos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Rosaceae/química , Antibacterianos/isolamento & purificação , Benzofuranos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Testes de Sensibilidade Microbiana , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologiaRESUMO
This research was carried out to study the secondary metabolites of endophytic fungus Aspergillosis fumigatus from Euphorbia royleana. The endophytic fungus A. fumigatus was fermented by solid fermentation,and purified by various chromatographic methods after extraction. The structures of the compounds were identified by1 H-NMR,13 C-NMR and HSQC,HMBC spectra and physicchemical properties. Three compounds were isolated and their structures were identified as 3-( 3,4-dihydroxybenzoyl)-5-( 3,4-dihydroxyphenyl)-6-methyl-5,6-dihydro-2 H-pyran-2-one( 1),hydroxysydonic acid( 2) and 11-hydroxysydonic acid( 3). Compound 1 is a new compound.
Assuntos
Aspergillus fumigatus/química , Euphorbia/microbiologia , Fenóis/isolamento & purificação , Endófitos/química , FermentaçãoRESUMO
A new benzylated alkamide, N-(3,4-dimethoxybenzyl)-9Z-oleamide (1), along with two known ones (2 and 3) were isolated from the roots of Lepidium meyenii collected from Lijiang, Yunnan Province of China. Their structures were elucidated by extensive spectroscopic analyses and the new compound further confirmed by a one-step synthesis. All the isolated alkamides were evaluated for their cytotoxicity against five human cancer cell lines. However, no significant activities were detected at concentrations up to 40 µM.
