| [PMID]: | 26654829 |
| [Au] Autor: | Ma J; Mi C; Wang KS; Lee JJ; Jin X |
| [Ad] Endereço: | Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China; Molecular Cancer Research Center, Yanbian University, Yanji 133002, Jilin Province, China. |
| [Ti] Título: | 4',6-Dihydroxy-4-methoxyisoaurone inhibits TNF-α-induced NF-κB activation and expressions of NF-κB-regulated target gene products. |
| [So] Source: | J Pharmacol Sci;130(2):43-50, 2016 Feb. |
| [Is] ISSN: | 1347-8648 |
| [Cp] País de publicação: | Japan |
| [La] Idioma: | eng |
| [Ab] Resumo: | The nuclear factor-κB (NF-κB) transcription factors control many physiological processes including inflammation, apoptosis, and angiogenesis. In our search for NF-κB inhibitors from natural resources, we identified 4',6-dihydroxy-4-methoxyisoaurone (ISOA) as an inhibitor of NF-κB activation from the seeds of Trichosanthes kirilowii. However, the mechanism by which ISOA inhibits NF-κB activation is not fully understood. In the present study, we demonstrated the effect of ISOA on NF-κB activation in TNF-α-stimulated HeLa cells. This compound suppressed NF-κB activation through the inhibition of IκB kinase (IKK) activation. ISOA also has an influence on upstream signaling of IKK through the inhibition of expression of adaptor proteins, TNF receptor-associated factor 2 (TRAF2) and receptor interacting protein 1 (RIP1). Consequently, ISOA blocked the phosphorylation and degradation of the inhibitor of NF-κB alpha (IκBα), and subsequent phosphorylation and nuclear translocation of p65. The suppression of NF-κB activation by ISOA led to the down-regulation of target genes involved in inflammation, proliferation, as well as potentiation of TNF-α-induced apoptosis. Taken together, this study extends our understanding on the mechanisms underlying the anti-inflammatory and anti-cancer activities of ISOA. Our findings provide new insight into the molecular mechanisms and a potential application of ISOA for inflammatory diseases as well as certain cancers. |
| [Mh] Termos MeSH primário: |
Expressão Gênica/efeitos dos fármacos
Expressão Gênica/genética
NF-kappa B/metabolismo
Sesquiterpenos/farmacologia
Fator de Necrose Tumoral alfa
|
| [Mh] Termos MeSH secundário: |
Proteínas Adaptadoras de Transdução de Sinal/genética
Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Apoptose/efeitos dos fármacos
Apoptose/genética
Proliferação Celular/efeitos dos fármacos
Proliferação Celular/genética
Células HeLa
Seres Humanos
Quinase I-kappa B/antagonistas & inibidores
Inflamação/tratamento farmacológico
Inflamação/genética
Neoplasias/tratamento farmacológico
Neoplasias/genética
Complexo de Proteínas Formadoras de Poros Nucleares/genética
Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo
Fosforilação/efeitos dos fármacos
Fitoterapia
Proteínas de Ligação a RNA/genética
Proteínas de Ligação a RNA/metabolismo
Sementes/química
Sesquiterpenos/isolamento & purificação
Fator 2 Associado a Receptor de TNF/genética
Fator 2 Associado a Receptor de TNF/metabolismo
Fator de Transcrição RelA/metabolismo
Trichosanthes/química
|
| [Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (4',6-dihydroxy-4-methoxyisoaurone); 0 (AGFG1 protein, human); 0 (Adaptor Proteins, Signal Transducing); 0 (NF-kappa B); 0 (Nuclear Pore Complex Proteins); 0 (RNA-Binding Proteins); 0 (Sesquiterpenes); 0 (TNF Receptor-Associated Factor 2); 0 (Transcription Factor RelA); 0 (Tumor Necrosis Factor-alpha); EC 2.7.11.10 (I-kappa B Kinase) |
| [Em] Mês de entrada: | 1612 |
| [Cu] Atualização por classe: | 161230 |
[Lr] Data última revisão:
| 161230 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 151215 |
| [St] Status: | MEDLINE |
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