4-O-Methylhonokiol Protects HaCaT Cells from TGF-β1-Induced Cell Cycle Arrest by Regulating Canonical and Non-Canonical Pathways of TGF-β Signaling.
10.4062/biomolther.2016.003
- Author:
Sang Cheol KIM
1
;
Jung Il KANG
;
Jin Won HYUN
;
Ji Hoon KANG
;
Young Sang KOH
;
Young Heui KIM
;
Ki Ho KIM
;
Ji Hee KO
;
Eun Sook YOO
;
Hee Kyoung KANG
Author Information
1. Department of Medicine, Jeju National University School of Medicine, Jeju 63243, Republic of Korea. pharmkhk@jejunu.ac.kr
- Publication Type:Original Article
- Keywords:
4-O-methylhonokiol;
Transforming growth factor-β1;
Cell cycle arrest;
Smads;
Reactive oxygen species;
NADPH oxidase 4
- MeSH:
Cell Cycle Checkpoints*;
Cell Cycle*;
Hair;
Humans;
Keratinocytes;
Magnolia;
NADPH Oxidase;
Phosphorylation;
Reactive Oxygen Species;
RNA, Messenger;
Signal Transduction
- From:Biomolecules & Therapeutics
2017;25(4):417-426
- CountryRepublic of Korea
- Language:English
-
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-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.
