Praeruptorin A reduces metastasis of human hepatocellular carcinoma cells by targeting ERK/MMP1 signaling pathway

Environ Toxicol. 2021 Apr;36(4):540-549. doi: 10.1002/tox.23059. Epub 2020 Nov 23.

Abstract

Praeruptorin A (PA) is one of the active ingredients found in the dried root of Peucedanum praeruptorum Dunn, has been reported to possess anticancer effects against various types of cancer. However, the effect of PA on human hepatocellular carcinoma (HCC) remains uncleared. In this study, our results indicated that PA did not induce cytotoxicity or alter cell cycle distribution in human HCC cells (Huh-7, SK-Hep-1, and PLC/PRF/5 cells). Instead, PA inhibited the migration and invasion of human HCC cells while downregulating the expression of matrix metalloproteinase-1 (MMP1) and activating the extracellular signal-regulated kinase (ERK) signaling pathways. Furthermore, blocking the ERK signaling pathway through siERK restored the expression of MMP1 and the invasive ability of PA-treated HCC cells. In conclusion, our results demonstrate the antimetastatic activity of PA against human HCC cells, supporting its potential as a therapeutic agent of HCC treatments.

Keywords: ERK; MMP1; hepatocellular carcinoma cells; metastatsis; praeruptorin A.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Culture Techniques
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Survival / drug effects
  • Coumarins / pharmacology*
  • Down-Regulation
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • MAP Kinase Signaling System / drug effects*
  • Matrix Metalloproteinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neoplasm Invasiveness
  • Tumor Stem Cell Assay

Substances

  • Antineoplastic Agents, Phytogenic
  • Coumarins
  • praeruptorin A
  • Extracellular Signal-Regulated MAP Kinases
  • MAPK3 protein, human
  • Mitogen-Activated Protein Kinase 3
  • MMP1 protein, human
  • Matrix Metalloproteinase 1