Biomol Ther.  2017 Jul;25(4):417-426. 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

  • 1Department of Medicine, Jeju National University School of Medicine, Jeju 63243, Republic of Korea.
  • 2R&D Center, Bioland Ltd., Cheonan 31257, Republic of Korea.
  • 3Freshwater Bioresources Utilization Division, Nakdonggang National Institute of Biological Resourecs, Sangju 37242, Republic of Korea.


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-β (TGF-β) signal pathway has an essential role in the regression induction of hair growth, the effect of 4-O-methylhonokiol on the TGF-β signal pathway has not yet been elucidated. We thus examined the effect of 4-O-methylhonokiol on TGF-β-induced canonical and noncanonical pathways in HaCaT human keratinocytes. When HaCaT cells were pretreated with 4-O-methylhonokiol, TGF-β1-induced G1/G0 phase arrest and TGF-β1-induced p21 expression were decreased. Moreover, 4-O-methylhonokiol inhibited nuclear translocation of Smad2/3, Smad4 and Sp1 in TGF-β1-induced canonical pathway. We observed that ERK phosphorylation by TGF-β1 was significantly attenuated by treatment with 4-O-methylhonokiol. 4-O-methylhonokiol inhibited TGF-β1-induced reactive oxygen species (ROS) production and reduced the increase of NADPH oxidase 4 (NOX4) mRNA level in TGF-β1-induced noncanonical pathway. These results indicate that 4-O-methylhonokiol could inhibit TGF-β1-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-β1-induced cell cycle arrest.


4-O-methylhonokiol; Transforming growth factor-β1; Cell cycle arrest; Smads; Reactive oxygen species; NADPH oxidase 4

MeSH Terms

Cell Cycle Checkpoints*
Cell Cycle*
NADPH Oxidase
Reactive Oxygen Species
RNA, Messenger
Signal Transduction
NADPH Oxidase
RNA, Messenger
Reactive Oxygen Species
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