Actein inhibits glioma growth via a mitochondria-mediated pathway

Cancer Biomark. 2017;18(4):329-338. doi: 10.3233/CBM-160095.

Abstract

Previous studies indicate that the triterpene glycoside Actein from the herb black cohosh inhibits growth of human breast cancer cells. This study sought to investigate the effects of Actein on glioma cell growth and explore the potential mechanisms. Our results showed that administration of Actein significantly inhibited glioma cell viability in a dose- and time-dependent manner. Actein also increasingly inhibited the colony formation processes in glioma U87 cells and U251 cells. Administration of Actein also induced mitochondria-related apoptosis by increasing expression of pro-apoptotic factors Bax, cleaved caspase-3, cleaved caspase-9 and cleaved poly (ADP-ribose) polymerase 1 (PARP1) as well as decreasing anti-apoptotic Bcl-2 expression in U87 cells and U251 cells. In a xenograft model of glioma, Actein suppressed tumor growth and consistently induced cell apoptosis with the same mechanisms observed in vitro. In all, this study is the first report to address the growth inhibitory effects of Actein on glioma growth and propose that mitochondria-mediated apoptosis pathway may underlie the biological activities of Actein in glioma. Our study suggests that administration of Actein may serve as a potent therapeutic strategy for treatment of glioma.

Keywords: Actein; apoptosis; glioma; growth; mitochondria.

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics*
  • Caspase 3 / genetics
  • Caspase 9 / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioma / drug therapy*
  • Glioma / genetics
  • Glioma / pathology
  • Humans
  • Mice
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Poly (ADP-Ribose) Polymerase-1 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Saponins / administration & dosage*
  • Signal Transduction / drug effects
  • Triterpenes / administration & dosage*
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / genetics

Substances

  • BAX protein, human
  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-bcl-2
  • Saponins
  • Triterpenes
  • bcl-2-Associated X Protein
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Caspase 3
  • Caspase 9
  • actein