Induction of apoptosis and cell cycle arrest in glioma cells by GL331 (a topoisomerase II inhibitor)

Anticancer Res. Nov-Dec 2005;25(6B):4203-8.

Abstract

Background: GL331 is a topoisomerase II inhibitor and, in this study, the effects of GL331 upon rat C6 glioma cells were investigated.

Materials and methods: The glioma cells were treated with GL331, then a cytotoxicity assay was done to evaluate the cytotoxic effects of GL331 and flow-activated cell sorter analysis was performed to analyze the cellular apoptosis and cell cycle distribution of the glioma cells. The expressions of p53, p21 and 14-3-3sigma in glioma cells treated with GL331 were investigated by Western blot analysis.

Results: GL331 was demonstrated to exert cytotoxic effects upon and induce apoptosis of the C6 glioma cells in a concentration- and time-dependent manner (p < 0.05). GL331 also caused the glioma cells to accumulate in the G2/M-phase of the cell cycle and increased the expressions of p53, p21 and 14-3-3sigma.

Conclusion: GL331 exerts cytotoxic effects and induces apoptosis in C6 glioma cells, accompanied by cell accumulation in the G2/M-phase and activation of p53, p21 and 14-3-3sigma.

MeSH terms

  • 14-3-3 Proteins / biosynthesis
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis
  • Enzyme Inhibitors / pharmacology
  • Etoposide / analogs & derivatives*
  • Etoposide / pharmacology
  • G2 Phase / drug effects
  • Glioma / drug therapy*
  • Glioma / enzymology
  • Glioma / metabolism
  • Glioma / pathology*
  • Rats
  • Topoisomerase II Inhibitors*
  • Tumor Suppressor Protein p53 / biosynthesis

Substances

  • 14-3-3 Proteins
  • Antineoplastic Agents, Phytogenic
  • Cyclin-Dependent Kinase Inhibitor p21
  • Enzyme Inhibitors
  • Topoisomerase II Inhibitors
  • Tumor Suppressor Protein p53
  • GL 331
  • Etoposide