Title:Erythropoietin Enhances the Cytotoxic Effect of Hydrogen Peroxide on Colon Cancer Cells
Volume: 18
Issue: 2
Author(s): Anna Tankiewicz-Kwedlo, Justyna M. Hermanowicz, Arkadiusz Surazynski, Wojciech Kwedlo, Dariusz Rozkiewicz, Krystyna Pawlak, Tomasz Domaniewski and Dariusz Pawlak
Affiliation:
Keywords:
Erythropoietin, hydrogen peroxide, colon cancer cells, DLD-1, confocal microscopy, erythropoietin receptor.
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.
Conclusion: These preclinical results suggest that Epo during chemotherapy or radiotherapy may possess
potential benefits in colon cancer patients.
