Lobetyolin Suppresses the Proliferation of Hepatocellular Carcinoma through Activating DUSP1-ERK1/2 Signaling Pathway

Biol Pharm Bull. 2024;47(10):1751-1758. doi: 10.1248/bpb.b24-00307.

Abstract

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer with limited treatment options. Lobetyolin (LBT), a polyacetylene glycoside mainly extracted from the roots of Codonopsis pilosula, has been reported to have anti-tumor efficancy in various cancers. However, the role of LBT as well as its underlying mechanisms in HCC remain unclear. Here we investigated the impact of LBT on the phenotype in HepG2 and Huh7 cells. We found that LBT significantly induced cell growth inhibition and mitochondria-dependent apoptosis in HCC cells. Moreover, LBT upregulated dual specificity phosphatase-1 (DUSP1) expression and knockingdown DUSP1 markedly attenuated those effects induce by LBT. Meanwhile, LBT decreased the phosphorylation level of extracellular signal-regulated kinase 1/2 (ERK1/2), a well-recognized downstream effector of DUSP1, and knockingdown DUSP1 partially recovered LBT-induced inactivation of ERK1/2. In conclusion, the present study indicated that LBT could induce cell death of HCC via promotion of DUSP1-mediated ERK1/2 inhibition. These data will help to establish the evidence of LBT to treat HCC.

Keywords: dual specificity phosphatase-1 (DUSP1); extracellular signal-regulated kinase 1/2 (ERK1/2); hepatocellular carcinoma; lobetyolin.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Dual Specificity Phosphatase 1* / genetics
  • Dual Specificity Phosphatase 1* / metabolism
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / pathology
  • MAP Kinase Signaling System* / drug effects

Substances

  • Dual Specificity Phosphatase 1
  • DUSP1 protein, human
  • Antineoplastic Agents, Phytogenic