2. Academic Validation
  3. Oroxylin A inhibits the migration of hepatocellular carcinoma cells by inducing NAG-1 expression

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

  • Acta Pharmacol Sin. 2022 Mar;43(3):724-734. doi: 10.1038/s41401-021-00695-4.
Tong-Xin Huo  # 1,  Xiao-Ping Wang  # 1,  Zhou Yu 1,  Bo Kong 1,  Yuan He 1,  Qing-Long Guo 2,  Xiao-Bo Zhang 3,  Lei Qiang 4 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
  • 2 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
  • 3 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China. zxb@cpu.edu.cn.
  • 4 State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China. lqiang@cpu.edu.cn.
  • 5 Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China. lqiang@cpu.edu.cn.
  • # Contributed equally.
PMID: 34117368 DOI: 10.1038/s41401-021-00695-4
Abstract

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.

Keywords

HDAC1; NAG-1; hepatocellular carcinoma; metastasis; oroxylin A.

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