Honokiol inhibits HIF pathway and hypoxia-induced expression of histone lysine demethylases.
Biochem Biophys Res Commun
; 422(3): 369-74, 2012 Jun 08.
Article
em En
| MEDLINE
| ID: mdl-22580280
ABSTRACT
Hypoxia-inducible-factor (HIF)-mediated expression of pro-angiogenic genes under hypoxic conditions is the fundamental cause of pathological neovascularization in retinal ischemic diseases and cancers. Recent studies have shown that histone lysine demethylases (KDMs) play a key role in the amplification of HIF signaling and expression of pro-angiogenic genes. Thus, the inhibitors of the HIF pathway or KDMs can have profound therapeutic value for diseases caused by pathological neovascularization. Here, we show that hypoxia-mediated expression of KDMs is a conserved process across multiple cell lines. Moreover, we report that honokiol, a biphenolic phytochemical extracted from Magnolia genus which has been used for thousands of years in the traditional Japanese and Chinese medicine, is a potent inhibitor of the HIF pathway as well as hypoxia-induced expression of KDMs in a number of cancer and retinal pigment epithelial cell lines. Further, treating the cells with honokiol leads to inhibition of KDM-mediated induction of pro-angiogenic genes (adrenomedullin and growth differentiation factor 15) under hypoxic conditions. Our results provide an evidence-based scientific explanation for therapeutic benefits observed with honokiol and warrant its further clinical evaluation for the treatment of pathological neovascularization in retinal ischemic diseases and cancers.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Compostos de Bifenilo
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Lignanas
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Inibidores da Angiogênese
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Fator 1 Induzível por Hipóxia
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Histona Desmetilases
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Neovascularização Patológica
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article