Noscapine sensitizes chemoresistant ovarian cancer cells to cisplatin through inhibition of HIF-1α

Cancer Lett. 2011 Jun 1;305(1):94-9. doi: 10.1016/j.canlet.2011.02.031. Epub 2011 Mar 21.

Abstract

Hypoxia-inducible factor 1 alpha (HIF-1α) is closely related with chemoresistance of solid tumors. The purpose of this study was to investigate the ability of noscapine to inhibit HIF-1α and sensitize ovarian cancer cells to cisplatin (DDP) under hypoxic conditions. Herein, we report that noscapine sensitized cobalt-induced chemoresistant ovarian cancer cells to DDP-induced apoptosis and inhibition of cell proliferation. Noscapine also promoted proteasome-mediated degradation of cobalt-stabilized HIF-1α protein, with subsequent inhibition of HIF-1 transcriptional activity. These data establish noscapine as a small molecule inhibitor of HIF-1α and provide an evidence for its combination with DDP in combating ovarian cancer chemoresistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Separation
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm* / drug effects
  • Drug Resistance, Neoplasm* / physiology
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors*
  • Noscapine / pharmacology*
  • Ovarian Neoplasms / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Noscapine
  • Cisplatin