Inhibitory Effect of Magnolol on TPA-Induced Skin Inflammation and Tumor Promotion in Mice
Inhibitory Effect of Magnolol on TPA-Induced Skin Inflammation and Tumor Promotion in Mice
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DOI：
10.1021/jf100601r
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发表时间：
2010-05-12
影响因子：
6.1
通讯作者：
Pan, Min-Hsiung
中科院分区：
文献类型：
--
作者：
Kuo, Daih-Huang;Lai, You-Syuan;Pan, Min-Hsiung
据报道，厚朴酚在体外和体内具有抗炎和抗肿瘤作用。在此，我们报道了厚朴酚对 12-O-十四烷酰佛波醇-13-乙酸酯 (TPA) 诱导的小鼠皮肤中诱导型一氧化氮合酶 (iNOS) 和环氧合酶-2 (COX-2) 表达的抑制作用的研究。我们发现，局部应用厚朴酚可有效抑制 TPA 刺激的小鼠皮肤中 iNOS 和 COX-2 mRNA 和蛋白质的转录激活。用厚朴酚预处理可通过阻断 I kappa B α 和 p65 的磷酸化以及随后 I kappa B α 的降解，减少 TPA 诱导的核因子 kappa B (NF kappa B) 亚基的核易位和 DNA 结合。此外，厚朴酚可以抑制 TPA 诱导的细胞外信号调节激酶 (ERK)1/2、p38 丝裂原激活蛋白激酶 (MAPK) 和磷脂酰肌醇 3-激酶 (PI3K)/Akt 的激活，这些激酶是 NF kappa B 的上游。此外，厚朴酚通过以下方式显着抑制 7,12-二甲基苯[a]蒽 (DMBA)/TPA 诱导的皮肤肿瘤形成： 20周时降低乳头状瘤的肿瘤多样性、肿瘤发生率和肿瘤大小。所有这些结果表明，厚朴酚是一种有效的抗肿瘤药物，其抑制作用是通过下调小鼠皮肤中炎症iNOS和COX-2基因表达来实现的，表明厚朴酚是一种能够预防炎症相关肿瘤发生的新型功能剂。
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-kappa B (NF kappa B) subunit and DNA binding by blocking the phosphorylation of I kappa B alpha and p65 and subsequent degradation of I kappa B alpha. 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 NF kappa B. 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.