Noscapine induces apoptosis in human glioma cells by an apoptosis-inducing factor-dependent pathway

Anticancer Drugs. 2008 Jul;19(6):553-63. doi: 10.1097/CAD.0b013e3282ffd68d.

Abstract

Previously, we identified noscapine as a small molecule inhibitor of the hypoxia-inducible factor-1 pathway in hypoxic human glioma cells and human umbilical vein endothelial cells. Noscapine is a nontoxic ingredient in cough medicine currently used in clinical trials for patients with non-Hodgkin's lymphoma or chronic lymphocytic leukemia to assess antitumor efficacy. Here, we have evaluated the sensitivity of four human glioma cell lines to noscapine-induced apoptosis. Noscapine was a potent inhibitor of proliferation and inducer of apoptosis. Induction of apoptosis was associated with activation of the c-jun N-terminal kinase signaling pathway concomitant with inactivation of the extracellular signal regulated kinase signaling pathway and phosphorylation of the antiapoptotic protein Bcl-2. Noscapine-induced apoptosis was associated with the release of mitochondrial proteins apoptosis-inducing factor (AIF) and/or cytochrome c. In some glioma cell lines, only AIF release occurred without cytochrome c release or poly (ADP-ribose) polymerase cleavage. Knock-down of AIF decreased noscapine-induced apoptosis. Our results suggest the potential importance of noscapine as a novel agent for use in patients with glioblastoma owing to its low toxicity profile and its potent anticancer activity.

Publication types

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

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis Inducing Factor / physiology*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin B / analysis
  • Cyclin B1
  • Cytochromes c / metabolism
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Noscapine / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / analysis

Substances

  • Apoptosis Inducing Factor
  • CCNB1 protein, human
  • Cyclin B
  • Cyclin B1
  • Proto-Oncogene Proteins c-bcl-2
  • Noscapine
  • Cytochromes c