Daphnetin inhibits the survival of hepatocellular carcinoma cells through regulating Wnt/β-catenin signaling pathway

Drug Dev Res. 2022 Jun;83(4):952-960. doi: 10.1002/ddr.21920. Epub 2022 Feb 7.

Abstract

Evidence has demonstrated that Daphnetin has antiangiogenesis activity, indicating it might be a new multi-targeted medication for cancer therapy. Here, we aimed to reveal Daphnetin role in hepatocellular carcinoma (HCC) progression and the underlying mechanism. Huh7 and SK-HEP-1, two human HCC cell lines were used in this study. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), colony formation, flow cytometry, and tumor-bearing experiments were applied to evaluate the effects of different concentrations of Daphnetin on cell viability, apoptosis, cell cycle, and in vivo tumor formation, respectively. Real-time PCR (Polymerase Chain Reaction)and western blotting were applied to measure the mRNA and protein levels of β-catenin. We observed that Daphnetin inhibited cell viability and tumorigenesis, promoted cell apoptosis, and induced a G1 phase arrest in a dose-dependent manner in both Huh7 and SK-HEP-1 cells, which were rescued by SKL2001, an activator of the Wnt/β-catenin signaling. Taken together, this study reveals that Daphnetin exerts an antitumor role in HCC through the inactivation of Wnt/β-catenin signaling.

Keywords: Daphnetin; apoptosis; cell cycle; tumor formation; viability.

MeSH terms

  • Apoptosis
  • Carcinoma, Hepatocellular* / drug therapy
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / drug therapy
  • Umbelliferones
  • Wnt Signaling Pathway / genetics
  • beta Catenin / genetics
  • beta Catenin / metabolism
  • beta Catenin / pharmacology

Substances

  • Umbelliferones
  • beta Catenin
  • daphnetin