Activity of LaSOM 65, a monastrol-derived compound, against glioblastoma multiforme cell lines

Anticancer Res. 2013 Oct;33(10):4463-8.

Abstract

Background/aim: Despite recent progress in glioblastoma treatment, prognosis is still poor. Monastrol is a kinesin spindle protein (KSP) inhibitor and anticancer effects for this molecule have been reported. Here we describe the effect of LaSOM 65, a monastrol derivated compound, against glioma cell lines.

Materials and methods: Cell counting, viability assay, lactate dehydrogenase (LDH) activity, cell-cycle analysis, immunofluorescence and organotypic hippocampal slice cultures were performed.

Results: LaSOM 65 reduced cell number and cell viability of gliomas cells, but did not cause arrest in the cell cycle at the G2/M phase. Measurement of LDH activity showed that LaSOM 65 induces necrosis after 48 h of treatment.

Conclusion: LaSOM 65 appears to a be promising new molecule to treat glioblastoma since it promotes a decrease of cell growth and cell viability of glioma cells in vitro and does not induces the neurotoxic characteristics of the anti-mitotic drugs currently used.

Keywords: Glioma; KSP inhibitors; LaSOM 65; antitumor activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Nucleus / drug effects
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • Glioblastoma
  • Hippocampus / drug effects
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Necrosis
  • Pyrimidines / pharmacology*
  • Rats
  • Thiones / pharmacology*
  • Tissue Culture Techniques
  • Tubulin / metabolism

Substances

  • 5-ethoxycarbonyl-6-methyl-4-(3-nitrophenyl)-3,4-dihydropyrimidin-2-(1H)-thione
  • Antineoplastic Agents
  • Pyrimidines
  • Thiones
  • Tubulin
  • L-Lactate Dehydrogenase