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

Biochemical and Biophysical Research Communications
Divya Teja VavilalaMridul Mukherji

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 a...Continue Reading

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Citations

Jul 6, 2013·International Journal of Pharmaceutics·Ramya Krishna VadlapatlaAshim K Mitra
Jun 4, 2013·Biochemical and Biophysical Research Communications·V K Chaithanya PonnaluriMridul Mukherji
Apr 15, 2015·Nature Communications·Vinodkumar B PillaiMahesh P Gupta
Jul 23, 2013·Biochemical and Biophysical Research Communications·V K Chaithanya PonnaluriMridul Mukherji
Aug 8, 2013·Biochemical and Biophysical Research Communications·Divya Teja VavilalaMridul Mukherji
Mar 6, 2019·International Journal of Molecular Sciences·Yoon-Mi LeeJi-Hong Lim
Dec 15, 2015·Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry·Chia-Hsien ChenTung-Hu Tsai
Jul 13, 2021·Chinese Journal of Natural Medicines·Cheng ChenLi-Gen Lin

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