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http://dx.doi.org/10.4062/biomolther.2016.003

4-O-Methylhonokiol Protects HaCaT Cells from TGF-β1-Induced Cell Cycle Arrest by Regulating Canonical and Non-Canonical Pathways of TGF-β Signaling  

Kim, Sang-Cheol (Department of Medicine, Jeju National University School of Medicine)
Kang, Jung-Il (Department of Medicine, Jeju National University School of Medicine)
Hyun, Jin-Won (Department of Medicine, Jeju National University School of Medicine)
Kang, Ji-Hoon (Department of Medicine, Jeju National University School of Medicine)
Koh, Young-Sang (Department of Medicine, Jeju National University School of Medicine)
Kim, Young-Heui (R&D Center, Bioland Ltd.)
Kim, Ki-Ho (R&D Center, Bioland Ltd.)
Ko, Ji-Hee (Department of Medicine, Jeju National University School of Medicine)
Yoo, Eun-Sook (Department of Medicine, Jeju National University School of Medicine)
Kang, Hee-Kyoung (Department of Medicine, Jeju National University School of Medicine)
Publication Information
Biomolecules & Therapeutics / v.25, no.4, 2017 , pp. 417-426 More about this Journal
Abstract
4-O-methylhonokiol, a neolignan compound from Magnolia Officinalis, has been reported to have various biological activities including hair growth promoting effect. However, although transforming growth factor-${\beta}$ (TGF-${\beta}$) signal pathway has an essential role in the regression induction of hair growth, the effect of 4-O-methylhonokiol on the TGF-${\beta}$ signal pathway has not yet been elucidated. We thus examined the effect of 4-O-methylhonokiol on TGF-${\beta}$-induced canonical and noncanonical pathways in HaCaT human keratinocytes. When HaCaT cells were pretreated with 4-O-methylhonokiol, TGF-${\beta}1$-induced G1/G0 phase arrest and TGF-${\beta}1$-induced p21 expression were decreased. Moreover, 4-O-methylhonokiol inhibited nuclear translocation of Smad2/3, Smad4 and Sp1 in TGF-${\beta}1$-induced canonical pathway. We observed that ERK phosphorylation by TGF-${\beta}1$ was significantly attenuated by treatment with 4-O-methylhonokiol. 4-O-methylhonokiol inhibited TGF-${\beta}1$-induced reactive oxygen species (ROS) production and reduced the increase of NADPH oxidase 4 (NOX4) mRNA level in TGF-${\beta}1$-induced noncanonical pathway. These results indicate that 4-O-methylhonokiol could inhibit TGF-${\beta}1$-induced cell cycle arrest through inhibition of canonical and noncanonical pathways in human keratinocyte HaCaT cell and that 4-O-methylhonokiol might have protective action on TGF-${\beta}1$-induced cell cycle arrest.
Keywords
4-O-methylhonokiol; Transforming growth factor-${\beta}1$; Cell cycle arrest; Smads; Reactive oxygen species; NADPH oxidase 4;
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