Quercetin, a potential inhibitor of the Plasma membrane Ca2+ ATPase

MANGIALAVORI, I. .; RINALDI, D.E; AMABLE, G; REY, O; ROSSI, J.P.; FERREIRA GOMES, M

Mar del Plata

Congreso; 51 Annual Meeting ARgentine Society for Biochemistry and Molecular Biology; 2015

Sociedad Argentina

Flavonoids are group of hydroxylated polycyclic molecules found in fruit and vegetables and found micromolars concentrations in human blood plasma. These have beneficial health effects, including cancer chemoprotection. One mechanism proposed to explain this is that they are able to induce apoptosis in cancer cells by inhibiting of kinases and Ca2+-ATPases. Apoptosis would initiate via a Ca2+-dependent mitochondrial pathway, which can be activated through an exaggerated elevation of cytosolic [Ca2+] ([Ca2+]cyt). In this sense, the plasma membrane calcium ATPase (PMCA) plays an essential role in maintaining intracellular Ca2+ homeostasis.The purpose of this work is to investigate to quercetin as a potent flavone inhibitor of PMCA and determine the mechanism of action.We evaluated the effect of quercetin on the variation of [Ca2+]cyt in HEK 293T cells. The results show that the rate of removal of Ca2+ is less in the presence of flavonoid respect to the control suggesting that those systems that remove calcium would be affected, including the PMCA. In order to study this effect directly on the PMCA we evaluated Ca2+-ATPase activity using vesicles and purified PMCA obtained from human erythrocytes. The results show that quercetin can inhibit the activity of PMCA in the micromolar concentration range.These results suggest that PMCA could be a specific target of flavonoids contributing to elevation of [Ca2+]cyt during cancer cells apoptosis.