Inhibition of integrin-linked kinase expression by emodin through crosstalk of AMPKα and ERK1/2 signaling and reciprocal interplay of Sp1 and c-Jun.
Cell Signal
; 27(7): 1469-77, 2015 Jul.
Article
em En
| MEDLINE
| ID: mdl-25889897
ABSTRACT
Despite the anti-cancer effect of emodin observed in several cancers, the underlying molecular mechanism remains to be elucidated. In this study, we showed that emodin-inhibited NSCLC cell growth and increased phosphorylation of AMPKα and ERK1/2. In addition, emodin-inhibited ILK protein expression. The overexpression of ILK reversed the effect of emodin on cell growth inhibition. Furthermore, the blockade of AMPK by compound C abrogated, while metformin, an activator of AMPK, strengthened the effect of emodin on the inhibition of ILK expression. Interestingly, the inhibitor of MAPK extracellular signaling-regulated kinase (ERK) kinase (MEK)/ERK1/2 (PD98059) attenuated emodin-induced phosphorylation of AMPKα. Moreover, emodin reduced the protein expression of Sp1 and AP-1 subunit c-Jun. Exogenous expression of Sp1 and c-Jun diminished emodin-reduced ILK protein expression. Emodin suppressed ILK promoter activity, which was not observed in cells overexpression of Sp1 and treated with compound C. Intriguingly, exogenous expression of c-Jun overcame the emodin-inhibited Sp1 protein expression. Collectively, our results demonstrate that emodin inhibits ILK expression through AMPKα-mediated reduction of Sp1 and c-Jun. Metformin enhances the effects of emodin. Exogenous expression of Sp1 and c-Jun resists emodin-inhibited ILK promoter activity and protein expression. In addition, the overexpression of c-Jun diminishes emodin-induced AMPKα signaling. Thus, the crosstalk of AMPKα and MEK/ERK1/2 signaling and the reciprocal interaction between Sp1 and c-Jun proteins contribute to the overall responses of emodin. This novel signaling axis may be a therapeutic potential for prevention and treatment of NSCLC.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Fator de Transcrição Sp1
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Emodina
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Proteínas Proto-Oncogênicas c-jun
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Proteínas Serina-Treonina Quinases
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Inibidores de Proteínas Quinases
Limite:
Humans
Idioma:
En
Revista:
Cell Signal
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
China