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

Hypoxia-inducible factor 1 alpha (HIF-1 alpha) is closely related with chemoresistance of solid tumors. The purpose of this study was to investigate the ability of noscapine to inhibit HIF-1 alpha 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-1 alpha protein, with subsequent inhibition of HIF-1 transcriptional activity. These data establish noscapine as a small molecule inhibitor of HIF-1 alpha and provide an evidence for its combination with DDP in combating ovarian cancer chemoresistance. (C) 2011 Elsevier Ireland Ltd. All rights reserved.