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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2012

Open Access 01-12-2012 | Research

Pro-death and pro-survival properties of ouabain in U937 lymphoma derived cells

Authors: Francesca Cuozzo, Marisa Raciti, Laura Bertelli, Rosanna Parente, Livia Di Renzo

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2012

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Abstract

Background

Epidemiological studies revealed significantly lower mortality rates in cancer patients receiving cardiac glycosides, which turned on interest in the anticancer properties of these drugs. However, cardiac glycosides have also been shown to stimulate cell growth in several cell types. In the present investigation we analyzed the pro-death and pro-survival properties of ouabain in the human lymphoma derived cell line U937.

Methods

ROS, intracellular Ca++, cell cycle were evaluated by loading the cells with fluorescent probes under cytofluorimetry. Cell counts and evaluation of trypan blue-excluding cells were performed under optic microscope. Protein detection was done by specific antibodies after protein separation from cellular lysates by SDS-PAGE and transfer blot.

Results

High doses of ouabain cause ROS generation, elevation of [Ca++]i and death of lymphoma derived U937 cells. Lower doses of OUA activate a survival pathway in which plays a role the Na+/Ca++-exchanger (NCX), active in the Ca++ influx mode rather than in the Ca++ efflux mode. Also p38 MAPK plays a pro-survival role. However, the activation of this MAPK does not appear to depend on NCX.

Conclusion

This investigation shows that the cardiac glycoside OUA is cytotoxic also for the lymphoma derived cell line U937 and that can activate a survival pathway in which are involved NCX and p38 MAPK. These molecules can represent potential targets of combined therapy.
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Metadata
Title
Pro-death and pro-survival properties of ouabain in U937 lymphoma derived cells
Authors
Francesca Cuozzo
Marisa Raciti
Laura Bertelli
Rosanna Parente
Livia Di Renzo
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2012
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-31-95

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