title: Antiproliferative and apoptotic effects of iron chelators on human cervical carcinoma cells.
abstract: OBJECTIVE
  Cervical carcinoma is a human papillomavirus (HPV)-associated cancer for which treatment options still mainly rely on surgical procedures, with or without adjuvant radiotherapy and chemotherapy. As iron may participate in the pathogenesis of viral infections and cancer in several ways, the present study was designed to investigate the effect of iron chelation on HPV-16- and HPV-18-positive cervical carcinoma cell lines.
  
  
  METHODS
  Desferrioxamine and deferiprone, two chemically unrelated iron chelators, were used to investigate the effect of iron chelation on SiHa and HeLa cells. Proliferation was investigated by cells counts, by [(3)H]thymidine uptake assay, and by immunostaining with Ki-67 and proliferating cell nuclear antigen (PCNA). Apoptosis was determined by morphological analysis, by a TUNEL assay, and by flow cytometry detecting FITC-conjugated annexin-V.
  
  
  RESULTS
  Desferrioxamine and deferiprone induced a time- and dose-dependent inhibition of SiHa and HeLa cell growth. The inhibition of cell growth was associated with a decrease in the expression of both stable and total PCNA and Ki-67, a proliferation marker whose expression may predict survival in uterine cervical carcinoma. TUNEL assay, flow cytometry with annexin-V-fluorescein, and morphological analysis indicated that iron chelation also induced a time- and dose-dependent apoptosis of both cell lines. This apoptotic effect was prevented by the addition of exogenous iron.
  
  
  CONCLUSIONS
  These results show that iron chelation inhibits the growth and induces the apoptosis of HPV-positive carcinoma cells. This suggests that iron chelators may represent a potential therapeutic approach for the management of cervical carcinoma.
authors.affiliation: Department of Dermatology, Erasme University Hospital, Brussels, B-1070, Belgium. tsimonar@ulb.ac.be
authors.forename: Thierry
authors.initials: T
authors.lastname: Simonart
authors.forename: Johan R
authors.initials: JR
authors.lastname: Boelaert
authors.forename: Roger
authors.initials: R
authors.lastname: Mosselmans
authors.forename: Graciela
authors.initials: G
authors.lastname: Andrei
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Noel
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Robert
authors.initials: R
authors.lastname: Snoeck
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D000077543:Deferiprone; D003676:Deferoxamine / Q000494:pharmacology*; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology*; D027383:Papillomaviridae / Q000145:classification / Q000378:metabolism; D030361:Papillomavirus Infections / Q000150:complications / Q000378:metabolism / Q000821:virology; D011728:Pyridones / Q000494:pharmacology*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000150:complications / Q000378:metabolism / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000821:virology
chemical_list: D006131:Growth Inhibitors; D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D003676:Deferoxamine