Regulatory effect of 4-O-methylhonokiol on TGF-β1-induced cell cycle arrest in human keratinocyte cell line (HaCaT)

Transforming growth factor-β (TGF-β) signal pathway has a pivotal role in the progression of catagen phase in hair growth cycle. 4-O-Methylhonokiol, a neolignan compound from Magnolia Officinalis, has various biological activites such as anti-inflammatory, neurite outgrowth activity and anti-acetylcholinesterase activity. Recently we have reported the hair-growth promoting effect of 4-O-methylhonokiol. However, the hair-growing mechanisms of 4-O-methylhonokiol on the TGF-β signal pathway have not yet been elucidated. We thus examined whether 4-O-methylhonokiol has an inhibitory effect on TGF-β signal pathway in HaCaT cells. When HaCaT cells were pretreated with 4-O-methylhonokiol, the expression of TGF-β1-induced p21 was decreased. Moreover, 4-O-methylhonokiol attenuated the nuclear translocation of Smad2/3, Smad4 and Sp1 activation. 4-O-Methylhonokiol reduced TGF-β1-induced activation of ERK. On the other hand, TGF-β has been reported to increase reactive oxygen species (ROS), and TGF-β1-induced growth arrest have been known to be mediated by oxidative stress. 4-O-methylhonokiol inhibited TGF-β1-induced ROS production and suppressed mRNA expression of NOX4. These results suggest that hair-growing activity of 4-O-methylhonokiol might be at least related to its modulatory action on TGF-β-induced cell cycle arrest and ROS production.

Keywords: 4-O-methylhonokiol; Magnolia. officinalis; TGF-β; HaCaT cells; cell cycle arrest, NOX4