title: 4-O-Methylhonokiol Protects HaCaT Cells from TGF-β1-Induced Cell Cycle Arrest by Regulating Canonical and Non-Canonical Pathways of TGF-β Signaling.
abstract: 4-O-methylhonokiol, a neolignan compound fromMagnolia 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.
authors.affiliation: Department of Medicine, Jeju National University School of Medicine, Jeju 63243, Republic of Korea.|Freshwater Bioresources Utilization Division, Nakdonggang National Institute of Biological Resourecs, Sangju 37242, Republic of Korea.
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Department of Medicine, Jeju National University School of Medicine, Jeju 63243, Republic of Korea.
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Kang
authors.affiliation: Department of Medicine, Jeju National University School of Medicine, Jeju 63243, Republic of Korea.
authors.forename: Jin-Won
authors.initials: JW
authors.lastname: Hyun
authors.affiliation: Department of Medicine, Jeju National University School of Medicine, Jeju 63243, Republic of Korea.
authors.forename: Ji-Hoon
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Department of Medicine, Jeju National University School of Medicine, Jeju 63243, Republic of Korea.
authors.forename: Young-Sang
authors.initials: YS
authors.lastname: Koh
authors.affiliation: R&D Center, Bioland Ltd., Cheonan 31257, Republic of Korea.
authors.forename: Young-Heui
authors.initials: YH
authors.lastname: Kim
authors.affiliation: R&D Center, Bioland Ltd., Cheonan 31257, Republic of Korea.
authors.forename: Ki-Ho
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Department of Medicine, Jeju National University School of Medicine, Jeju 63243, Republic of Korea.
authors.forename: Ji-Hee
authors.initials: JH
authors.lastname: Ko
authors.affiliation: Department of Medicine, Jeju National University School of Medicine, Jeju 63243, Republic of Korea.
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Yoo
authors.affiliation: Department of Medicine, Jeju National University School of Medicine, Jeju 63243, Republic of Korea.
authors.forename: Hee-Kyoung
authors.initials: HK
authors.lastname: Kang
keywords: 4-O-methylhonokiol; Cell cycle arrest; NADPH oxidase 4; Reactive oxygen species; Smads; Transforming growth factor-β1