Hydrogen Peroxide-Induced Secreted Frizzled-Related Protein 1 Gene Demethylation Contributes to Hydrogen Peroxide-Induced Apoptosis in Human U251 Glioma Cells

DNA Cell Biol. 2017 May;36(5):347-353. doi: 10.1089/dna.2016.3594. Epub 2017 Feb 28.

Abstract

Glioblastoma multiforme is a type of central nervous system tumor with extremely poor prognosis. Previously, hydrogen peroxide (H2O2), which promotes the oxidative stress response, has been reported to induce the apoptosis of glioma cells. Recently, secreted frizzled-related protein 1 (SFRP1) has been shown to be associated with various types of malignant tumors and with H2O2-induced oxidative stress in cardiomyocytes by negatively regulating the Wnt signaling pathway. This study aimed to explore SFRP1 expression and its roles in H2O2-induced apoptosis in human glioma cells. We found that the SFRP1 level was decreased in several human glioma cell lines, including U87, U251, and SW1783 cells. In U251 cells, SFRP1 could function as a cancer suppressor gene, and the growth of U251 cells could be inhibited not only by H2O2 but also by the overexpression of SFRP1. Furthermore, we demonstrated that H2O2-induced SFRP1 gene demethylation partially contributed to H2O2-induced U251 cell apoptosis, which was verified by studies using an SFRP inhibitor (WAY-316606). Our research identified that H2O2-induced SFRP1 gene demethylation contributes to H2O2-induced apoptosis in human U251 glioma cells.

Keywords: U251 cells; cell apoptosis; demethylation; hydrogen peroxide; secreted frizzled-related protein 1.

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / genetics*
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cells, Cultured
  • DNA Methylation / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Hydrogen Peroxide / pharmacology*
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism

Substances

  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • SFRP1 protein, human
  • Hydrogen Peroxide