Oroxylin A inhibits the migration of hepatocellular carcinoma cells by inducing NAG-1 expression

• 作者: Tong-xin Huo Xiao-ping Wang Zhou Yu Bo Kong Yuan He Qing-long Guo Xiao-bo Zhang Lei Qiang
• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2022,（3）
• 所属期刊栏目: Chemotherapy
• 页码范围: 724-734
• 页数: 11页
• 语种: 英文

摘要

Hepatocellular carcinoma(HCC),the most prevalent liver cancer,is considered one of the most lethal malignancies with a dismal outcome mainly due to frequent intrahepatic and distant metastasis.In the present study,we demonstrated that oroxylin A,a natural product extracted from Scutellaria radix,significantly inhibits transforming growth factor-beta1(TGF-β1)-induced epithelial-mesenchymal transition(EMT)and metastasis in HCC.Oroxylin A blocked the TGF-β1/Smad signaling via upregulating the non-steroidal anti-inflammatory drug-activated gene-1(NAG-1)expression.Oroxylin A promoted NAG-1 transcription by regulating the acetylation of CCAAT/enhancer binding protein β(C/EBPβ),a transcription factor that binds to the NAG-1 promoter.In terms of the underlying mechanism,oroxylin A may interact with histone deacetylase 1(HDAC1)by forming hydrogen bonds with GLY149 residue and induce proteasome-mediated degradation of HDAC1 subsequently impairing HDAC1-mediated deacetylation of C/EBPβ and promoting the expression of NAG-1.Taken together,our findings revealed a previously unknown tumor-suppressive mechanism of oroxylin A.Oroxylin A should be further investigated as a potential clinical candidate for inhibiting HCC metastasis.