Selective Wnt/β-catenin Small-molecule Inhibitor CWP232228 Impairs Tumor Growth of Colon Cancer

Anticancer Res. 2019 Jul;39(7):3661-3667. doi: 10.21873/anticanres.13514.

Abstract

Background/aim: To explore the possibility of a selective small-molecule β-catenin inhibitor, CWP232228, as a potential therapeutic drug in the treatment of colorectal cancer (CRC).

Materials and methods: The effect of CWP2228 on HCT116 cells was analysed in vitro via flow cytometry, western immunoblotting, and luciferase reporter assays. NOD-scid IL2Rgammanull mice were employed for an in vivo xenograft study to validate the in vitro studies.

Results: CWP232228 treatment decreased the promoter activity and nuclear expression of β-catenin and induced a significant cytotoxic effect in HCT116 cells. CWP232228 treatment induced apoptosis and cell-cycle arrest in the G1 phase of the cell cycle. Furthermore, CWP232228 decreased the expression of aurora kinase A, c-Myc, cyclin D1 and microphthalmia-associated transcription factor. Lastly, CWP232228 also inhibited the growth of xenografted colon cancer cells in mice.

Conclusion: Collectively, CWP232228 may be used as a potential therapeutic drug in CRC.

Keywords: CWP232228; Colorectal cancer; apoptosis; cell cycle; β-catenin inhibitor.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Azabicyclo Compounds / pharmacology*
  • Azabicyclo Compounds / therapeutic use
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • HCT116 Cells
  • Humans
  • Male
  • Mice, Inbred NOD
  • Mice, SCID
  • Organophosphates / pharmacology*
  • Organophosphates / therapeutic use
  • Tumor Burden / drug effects
  • Wnt Signaling Pathway / drug effects
  • beta Catenin / antagonists & inhibitors*

Substances

  • Antineoplastic Agents
  • Azabicyclo Compounds
  • CTNNB1 protein, human
  • CWP232228
  • Organophosphates
  • beta Catenin