Triptolide inhibits cell proliferation and tumorigenicity of human neuroblastoma cells

Mol Med Rep. 2015 Feb;11(2):791-6. doi: 10.3892/mmr.2014.2814. Epub 2014 Oct 29.

Abstract

Triptolide is a diterpene triepoxide, extracted from the Chinese herb Tripterygium wilfordii Hook F, which has been shown to have antitumor activity in a number of cancers. Neuroblastoma is an aggressive extracranial pediatric solid tumor, with significant chemotherapeutic resistance. In this study, triptolide was hypothesized to be a potential therapeutic agent for neuroblastoma. The effects of triptolide on neuroblastoma cell growth and tumor development were investigated. Cell growth and proliferation were evaluated using a cell counting kit‑8 assay and a 5-bromo-2-deoxyuridine staining assay. Cell cycle and apoptosis were detected by flow cytometry. Reverse transcription‑quantitative polymerase chain reaction was conducted to detect the expression levels of the apoptosis‑associated proteins, caspase‑3 and caspase‑9. The tumorigenicity of neuroblastoma cells was assessed by a soft agar clonogenic assay and an in vivo tumorigenic assay. The results demonstrated that exposure of BE(2)‑C human neuroblastoma cells to triptolide resulted in a reduction in cell growth and proliferation, and the induction of cell death and apoptosis, together with cell cycle arrest in the S phase. A soft agar assay indicated that triptolide inhibited the colony‑forming ability of BE(2)‑C neuroblastoma cells. The xenograft experiment showed that triptolide significantly reduced tumor growth and development in vivo. The data suggested that this Chinese herb may be a potential novel chemotherapeutic agent for neuroblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Apoptosis / drug effects
  • Carcinogenesis / drug effects*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 9 / genetics
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Diterpenes / pharmacology*
  • Epoxy Compounds / pharmacology
  • Female
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology
  • Phenanthrenes / pharmacology*
  • S Phase Cell Cycle Checkpoints / drug effects
  • Transplantation, Heterologous
  • Tripterygium / chemistry
  • Tripterygium / metabolism

Substances

  • Antineoplastic Agents, Alkylating
  • Diterpenes
  • Epoxy Compounds
  • Phenanthrenes
  • triptolide
  • Caspase 3
  • Caspase 9