Effect of ferric ions on reactive oxygen species formation, cervical cancer cell lines growth and E6/E7 oncogene expression

Toxicol In Vitro. 2011 Feb;25(1):160-6. doi: 10.1016/j.tiv.2010.10.013. Epub 2010 Oct 29.


As iron ions may participate in the pathogenesis of cancer and viral infections, the aim of this study was to monitor their influence on proliferation, E6 and E7 oncogene expression and reactive oxygen species (ROS) production in two human papilloma virus (HPV) positive cervical carcinoma cell lines (HeLa and SiHa) and one HPV negative vulvar cell line (A431). The anti-anaemic drug, ferric-sorbitol-citric acid complex (FSC) as a source of Fe(III) ions was used. Cells were treated with FSC at the concentrations between 0.001 and 1 mM Fe(III) for different time periods. Fe(III) ions inhibited the viability of HeLa and A431 cells while it had no influence on SiHa cells. Furthermore, Fe(III) treatment showed a time-dependent and a higher stimulatory effect on E6/E7 expression in SiHa cells than in HeLa cells. Fe(III) ion treatment with concentrations lower than 0.1mM showed a time and a concentration dependent intracellular ROS production in all tested cell lines, while the treatment with 1mM concentration decreased ROS production in all tested cell lines. In conclusion, Fe(III) ion treatment apart from having an anti-tumour effect, as we previously described, enhances survival of HPV 16-positive cells and might be associated with HPV oncogenesis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / analysis
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Citrates / pharmacology
  • Culture Media, Conditioned / chemistry
  • Female
  • Ferric Compounds / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Viral / drug effects*
  • Human papillomavirus 16 / isolation & purification
  • Humans
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / metabolism*
  • Osmolar Concentration
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus E7 Proteins / metabolism*
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Time Factors
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / virology


  • Antineoplastic Agents
  • Citrates
  • Culture Media, Conditioned
  • E6 protein, Human papillomavirus type 16
  • Ferric Compounds
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • RNA, Messenger
  • Reactive Oxygen Species
  • Repressor Proteins
  • ferric-sorbitol-citrate
  • oncogene protein E7, Human papillomavirus type 16