Noscapine induces mitochondria-mediated apoptosis in gastric cancer cells in vitro and in vivo

Cancer Chemother Pharmacol. 2011 Mar;67(3):605-12. doi: 10.1007/s00280-010-1356-3. Epub 2010 May 21.

Abstract

Purpose: Noscapine plays an important role in the regulation of cell growth and death. It has been reported to potentiate the anti-tumor effect by inducing apoptosis in various malignant cells. However, the mechanism of inducing apoptosis in gastric cancer cells by this agent remains to be clarified.

Methods: In the study, we investigated the signaling pathways by which noscapine induces apoptosis in gastric cancer cell lines. Apoptosis of four human gastric cancer cell lines was induced by treatment with noscapine.

Results: Our results indicate that noscapine induced a dose-dependent apoptosis of these cells. The treatment with noscapine upregulated Bax and Cytochrome c (Cyt-c) protein, downregulated Bcl-2 protein. Caspase-3 and caspase-9 were activated, suggesting that the apoptosis is mediated by mitochondrial pathways. Moreover, in xenograft tumor mouse model, noscapine injection successfully inhibited the tumor growth via apoptosis induction which was demonstrated by TUNEL assay.

Conclusions: These data of the study suggest that noscapine induces apoptosis in gastric cancer cells via mitochondrial pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Cytochromes c / genetics
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Humans
  • In Situ Nick-End Labeling
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mitochondria / metabolism*
  • Noscapine / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Up-Regulation
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / genetics

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Noscapine
  • Cytochromes c
  • Caspase 3
  • Caspase 9