Isocostunolide inhibited glioma stem cell by suppression proliferation and inducing caspase dependent apoptosis

Bioorg Med Chem Lett. 2017 Jul 1;27(13):2863-2867. doi: 10.1016/j.bmcl.2017.04.075. Epub 2017 Apr 26.

Abstract

Glioblastoma multiform (GBM) is a highly aggressive brain tumor with poor life expectancy, and glioma stem cells (GSCs) are a small population of tumor cells existed in GBM, in which GSCs response to drive GBM recurrence, invasion and contribute to the anti-cancer resistance. GSCs have been identified and developed as a therapeutic target for GBM and can be used in drugs screening. Isocostunolide is a natural sesquiterpenoid and contained abundant resource in medicinal plants, but the anti-cancer efficacies of it against GSCs are still unexplored. In this investigation, the anti-tumor activity of isocostunolide against GSCs was investigated and the result demonstrated that it inhibited the growth of GSCs (GSC-3#, GSC-12#, GSC-18#) significantly with an IC50 value of 2.80μg/ml, 2.61μg/ml, 1.07μg/ml, respectively. In further mechanism study, isocostunolide inhibited GSCs cell proliferation, induced GSCs apoptosis significantly, as well as increased the proportion of the cleavage of caspase-3. The result suggested that isocostunolide induced GSCs apoptosis via the caspase dependent apoptotic pathway. Moreover, isocostunolide damaged GSCs colony formation capacity significantly and exhibited the anti-cancer efficacy against GSCs in vitro.

Keywords: Apoptosis; Cell proliferation; Colony formation; Glioma stem cells; Isocostunolide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Caspase 3 / metabolism*
  • Caspase Inhibitors / chemical synthesis
  • Caspase Inhibitors / chemistry
  • Caspase Inhibitors / pharmacology*
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • Molecular Structure
  • Sesquiterpenes / chemical synthesis
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Caspase Inhibitors
  • Sesquiterpenes
  • costunolide
  • Caspase 3