Caspase-dependent signaling underlies glioblastoma cell death in response to the fungal metabolite, fusarochromanone

Int J Mol Med. 2014 Sep;34(3):880-5. doi: 10.3892/ijmm.2014.1842. Epub 2014 Jul 9.

Abstract

Fungal metabolites continue to show promise as a viable class of anticancer agents. In the present study, we investigated the efficacy of the fungal metabolite, fusarochromanone (FC101), for its antitumor activities in glioblastomas, which have a median survival of less than two years and a poor clinical response to surgical resection, radiation therapy and chemotherapy. Using clinically applicable doses, we demonstrated that FC101 induced glioblastoma apoptotic cell death via caspase dependent signaling, as indicated by the cleavage of poly(ADP-ribose) polymerase, glioblastoma (PARP). FC101 also induced differential reactive oxygen species (ROS) levels in glioblastoma cells, contrasting a defined role of oxidative stress in apoptotic cell death observed with other fungal metabolites. Furthermore, the antitumorigenic effects of FC101 on tumor cell migration were assessed. Cell migration assays revealed that FC101 significantly reduced the migratory capacity of glioblastomas, which are incredibly invasive tumors. Taken together, the present study establishes FC101 as a candidate anticancer agent for the cooperative treatment of glioblastomas.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinin / metabolism
  • Brain Neoplasms / enzymology*
  • Brain Neoplasms / pathology*
  • Caspases / metabolism*
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chromones / pharmacology*
  • Enzyme-Linked Immunosorbent Assay
  • Glioblastoma / enzymology*
  • Glioblastoma / pathology*
  • Humans
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects*
  • Time Factors

Substances

  • Chromones
  • Reactive Oxygen Species
  • Actinin
  • Caspases
  • fusarochromanone