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Honokiol inhibits HIF pathway and hypoxia-induced expression of histone lysine demethylases.

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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Vavilala DT,Ponnaluri VK,Vadlapatla RK,Pal D,Mitra AK,Mukherji M

doi

10.1016/j.bbrc.2012.04.143

subject

Has Abstract

pub_date

2012-06-08 00:00:00

pages

369-74

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(12)00832-7

journal_volume

422

pub_type

杂志文章

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