Evaluation of the influence of FXYD2 on the Antitumoral Effects of Cardiotonic Steroids through Na, K-ATPase.
FXYD2, Na,K-ATPase, cancer, cardiotonic steroids
Cardiotonic steroids have been used as cardiotonic drugs for over 200 years and several current studies have shown interesting anti-tumoral effects over different cell cultures. The mechanism of action of these compounds has been attributed to their ability to interact with Na, K-ATPase and initiate specific signaling cascades and have been described as a target for anticancer drug development. FXYD2, also known as Na, K-ATPase gamma subunit may be participating in the structure of the receptor site for cardiac steroid binding and it is abnormally expressed in some cancer cell lines as such in lung carcinoma cells (A549 and H460) but not in healthy lung cells. Here we evaluated the effects of three cardiotonic steroids (ouabain, digoxin and digitoxin) in lung carcinoma cells and whether FXYD2 can influence the sensitivity of these compounds on Na, K-ATPase. All cardiotonic steroids were able to significantly reduce the viability in lung carcinoma cells. In addition, the presence of exogenously added FXYD2 make the tumor cells (A549 and H460) better respond to cardiotonic steroids anti-proliferative effect. Our data suggest that the FXYD2 peptide appears to increase the sensitivity of cardiotonic steroid binding on Na, K-ATPase, which in turn confirm the status of this enzyme as an important target for the development of antitumoral drugs, especially in malignant tumors which can overexpress FXYD2. In addition, cardiotonic steroids can be a potential therapeutic agent and FXYD2 appears to have a role as an important adjunct in this process.