title: Erythropoietin Enhances the Cytotoxic Effect of Hydrogen Peroxide on Colon Cancer Cells.
abstract: BACKGROUND
  Cancer patients treated with alkylating agents and radiotherapy are exposed to high level of reactive oxygen species (ROS) in tissues. ROS can involve superoxide free radicals, peroxynitrite, singlet oxygen, nitric oxide and hydrogen peroxide. It is well documented that increased exposure to oxygen through a high metabolic rate could lead to a shortened life span. Ionizing radiation, use of drugs and the development of cancer can lead to cancer-induced anemia. Recombinant human erythropoietin (Epo) supplementation is one of the methods for treating anemia. Erythropoietin through an increase in the number of erythrocytes, improves oxygenation tissue. The aim of this work was to study the effect of Epo on colon adenocarcinoma cells (DLD-1) given alone or in combination with hydrogen peroxide (H2O2). Cell proliferation and number were measured.
  
  
  METHODS
  Expression of EpoR, Bcl-2 and Akt1 protein was assessed by RT-PCR, Western blot, and confocal microscopy.
  
  
  RESULTS
  The results show that the coadministration of Epo and H2O2 indicates antitumor action, which occurs via a dose-dependent inhibition of DLD-1 cell growth and proliferation. Moreover, the coadministration of Epo and H2O2 resulted in a decrease of cell numbers, as well as Bcl-2 expression. The incubation of DLD-1 cells with those agents led to a decrease in EpoR and phosphorylated EpoR expression and an increase in Akt1 and phosphorylated Akt expression. The addition of Epo to H2O2 intensified the cytotoxic effect of the latter.
  
  
  CONCLUSIONS
  These preclinical results suggest that Epo during chemotherapy or radiotherapy may possess potential benefits in colon cancer patients.
authors.affiliation: Department of Monitored Pharmacotherapy Medical University of Bialystok, Mickiewicza 2C, 15-222 Białystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Tankiewicz-Kwedlo
authors.forename: Justyna M
authors.initials: JM
authors.lastname: Hermanowicz
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Surazynski
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kwedlo
authors.forename: Dariusz
authors.initials: D
authors.lastname: Rozkiewicz
authors.forename: Krystyna
authors.initials: K
authors.lastname: Pawlak
authors.forename: Tomasz
authors.initials: T
authors.lastname: Domaniewski
authors.forename: Dariusz
authors.initials: D
authors.lastname: Pawlak
mesh_terms: D002452:Cell Count; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C554270:EPO protein, human; D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt
keywords: DLD-1; Erythropoietin; colon cancer cells; confocal microscopy; erythropoietin receptor; hydrogen peroxide