Format

Send to

Choose Destination
Life Sci. 2015 Sep 15;137:142-9. doi: 10.1016/j.lfs.2015.07.022. Epub 2015 Jul 30.

Erythropoietin protects neuroblastoma cells against etoposide and vincristine by activating ERK and AKT pathways but has no effect in kidney cells.

Author information

1
Departamento de Biología Molecular y Biotencología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, D.F. CP 04510, Mexico; Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México, Unidad de Posgrado, Edificio B Primer Piso, Ciudad Universitaria, México, D.F. CP 04510, Mexico.
2
Departamento de Biología Molecular y Biotencología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, D.F. CP 04510, Mexico.
3
Departamento de Biología Molecular y Biotencología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, D.F. CP 04510, Mexico. Electronic address: lrochaz@biomedicas.unam.mx.

Abstract

AIMS:

Chemotherapy induces anaemia in neuroblastoma patients. Cancer-associated anaemia may be treated with recombinant erythropoietin. However, the potential effects of erythropoietin on neuroblastoma and kidney cells have not been extensively evaluated. The present study was designed to investigate the effect of erythropoietin on the proliferation, and protection against vincristine- and etoposide-induced cell death in neuroblastoma (MSN), and embryonic kidney (HEK 293) cells.

MAIN METHODS:

The expression of erythropoietin and its receptor in MSN and HEK 293 was analysed by RT-PCR, immunocytochemistry, and Western blotting. The effect of erythropoietin on cell viability and proliferation was evaluated by the MTT assay, and by the Click-iT EdU Alexa Fluor 647 kit, respectively. For the cyto-protective assays, cells were incubated with erythropoietin before etoposide and vincristine treatment. Activation of signalling pathways was studied by Western blotting.

KEY FINDINGS:

MSN and HEK 293 cells expressed the erythropoietin receptor, but not erythropoietin. Erythropoietin induced proliferation and protection against vincristine and etoposide in MSN cells. HEK 293 cells were not affected by erythropoietin. Erythropoietin showed an anti-apoptotic effect which was dependent on the activation of ERK1/2 and AKT. HEK 293 cells presented constitutively phosphorylated AKT, and showed no activation of ERK1/2 upon erythropoietin stimulation.

SIGNIFICANCE:

These results indicate that erythropoietin induces proliferation of MSN cells, and that it can ameliorate vincristine- and etoposide-induced apoptosis of these cells. Erythropoietin-mediated neuroprotection was regulated by the combined effect of the ERK1/2 and AKT signalling pathways. Our findings provide further insights into the potential effect of erythropoietin on neuroblastoma cells.

KEYWORDS:

Erythropoietin; Etoposide; Neuroblastoma; Neuroprotection; Vincristine

PMID:
26232556
DOI:
10.1016/j.lfs.2015.07.022
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center