Gambogic acid induces apoptotic cell death in T98G glioma cells

Bioorg Med Chem Lett. 2016 Feb 1;26(3):1097-1101. doi: 10.1016/j.bmcl.2015.11.043. Epub 2015 Nov 14.

Abstract

Gambogic acid (GA), a natural product with a xanthone structure, has a broad range of anti-proliferative effects on cancer cell lines. We evaluated GA for its cytotoxic effects on T98G glioblastoma cells. GA exhibited potent anti-proliferative activity and induced apoptosis in T98G glioblastoma cells in a dose-dependent manner. Incubation of cells with GA revealed apoptotic features including increased Bax and AIF expression, cytochrome c release, and cleavage of caspase-3, -8, -9, and PARP, while Bcl-2 expression was downregulated. Furthermore, GA induced reactive oxygen species (ROS) generation in T98G cells. Our results indicate that GA increases Bax- and AIF-associated apoptotic signaling in glioblastoma cells.

Keywords: Anticancer; Apoptosis; Gambogic acid; Glioblastoma; Reactive oxygen species (ROS).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cytochromes c / metabolism
  • Down-Regulation / drug effects
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Xanthones / chemistry*
  • Xanthones / isolation & purification
  • Xanthones / pharmacology

Substances

  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Xanthones
  • gambogic acid
  • Cytochromes c
  • Caspase 3
  • Caspase 8
  • Caspase 9