Cyanidin inhibits glioma stem cells proliferation through the Wnt signaling pathway

Int J Neurosci. 2024 Aug;134(8):858-865. doi: 10.1080/00207454.2022.2154669. Epub 2022 Dec 11.

Abstract

Background: Cyanidin has a protective effect on the nervous system and has been reported to treat tumor effectively. However, its impact on glioma stem cells (GSC) is unknown.

Methods: Using seven GSC lines, the anti-tumor effect of cyanidin is tested. The effect of cyanidin on the cell viability in each cell line is evaluated. Wnt signaling pathway-related genes are checked after treatment of cyanidin. Cytoplasmic/nuclear β-catenin protein levels post cyanidin treatment is detected. Protein levels of c-Myc after cyanidin treatment are determined. Twist1 and Snail1 protein levels after cyanidin treatment are checked as well.

Results: Cyanidin significantly reduces the cell viability of all GSCs, and exhibited the most substantial effect in GBM2 but no apparent effect in 293T cells. It can regulate the Wnt signaling pathway of all GSC lines. In the GBM2, GBM7, G166, and G179 cell lines, there is upregulation of WNT1 and MYC genes, while in the G144 and GliNS2 cell line, these two genes are down-regulated after cyanidin treatment. Cytoplasmic and nuclear protein levels of β-catenin in all cell lines are down-regulated. Cyanidin treatment significantly decreases the protein level for c-Myc in the GBM2 cell line compared with untreated cells, not in G144 or GliNS2 cells. Furthermore, cyanidin strongly reduces the expression of Twist1 and Snail1 in GBM2, G179, and G144 cell lines, while the GliNS2 cells show an opposite change in the cytoplasm and no change in nuclear.

Conclusion: Cyanidin exerts an anti-tumor effect in glioma stem cell lines, probably through the Wnt signaling pathway.

Keywords: Glioma; Wnt signal; cyanidin; glioma cell line; resveratrol.

MeSH terms

  • Anthocyanins* / pharmacology
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Cell Survival / drug effects
  • Glioma* / drug therapy
  • Glioma* / metabolism
  • Humans
  • Neoplastic Stem Cells* / drug effects
  • Neoplastic Stem Cells* / metabolism
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-myc / metabolism
  • Snail Family Transcription Factors / metabolism
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism
  • Wnt Signaling Pathway* / drug effects
  • beta Catenin / drug effects
  • beta Catenin / metabolism

Substances

  • Anthocyanins
  • cyanidin
  • beta Catenin
  • Twist-Related Protein 1
  • TWIST1 protein, human
  • Snail Family Transcription Factors
  • SNAI1 protein, human
  • Proto-Oncogene Proteins c-myc
  • Nuclear Proteins