Inhibitory effect of magnolol on TPA-induced skin inflammation and tumor promotion in mice.
Magnolol has been reported to have an anti-inflammatory and antitumor effect in vitro and in vivo. Herein, we report the investigation of the inhibitory effects of magnolol on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in mouse skin. We found that the topical application of magnolol effectively inhibited the transcriptional activation of iNOS and COX-2 mRNA and proteins in mouse skin stimulated by TPA. Pretreatment with magnolol resulted in the reduction of TPA-induced nuclear translocation of the nuclear factor-kappaB (NFkappaB) subunit and DNA binding by blocking the phosphorylation of IkappaBalpha and p65 and subsequent degradation of IkappaBalpha. In addition, magnolol can suppress TPA-induced activation of extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K)/Akt, which are upstream of NFkappaB. Moreover, magnolol significantly inhibited 7,12-dimethylbene[a]anthracene (DMBA)/TPA-induced skin tumor formation by reducing the tumor multiplicity, tumor incidence, and tumor size of papillomas at 20 weeks. All these results revealed that magnolol is an effective antitumor agent and that its inhibitory effect is through the down-regulation of inflammatory iNOS and COX-2 gene expression in mouse skin, suggesting that magnolol is a novel functional agent capable of preventing inflammation-associated tumorigenesis.
Kuo
Daih-Huang
DH
Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung, Taiwan. kuo0939@gmail.com
Lai
You-Syuan
YS
Lo
Chih-Yu
CY
Cheng
An-Chin
AC
Wu
Hou
H
Pan
Min-Hsiung
MH
D000818:Animals; D001483:Base Sequence; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity*; D017931:DNA Primers; D003877:Dermatitis, Contact / Q000209:etiology / Q000517:prevention & control*; D024202:Electrophoretic Mobility Shift Assay; D017705:Lignans / Q000494:pharmacology*; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D001713:Biphenyl Compounds; D002273:Carcinogens; D017931:DNA Primers; D017705:Lignans; C005498:magnolol; D013755:Tetradecanoylphorbol Acetate