Pseudopterosin A ‐ an Atypical Antagonist of Adenosine A2B Receptors that Accelerates Angiogenesis

Abstract

SummaryPseudopterosins are known anti‐inflammatory and anti‐microbial agents, isolated from the soft coral, Pseudopterogorgia elisabethae. We report pseudopterosins as activators of cell proliferation in human umbilical vein endothelial cells (HUVEC), a cellular model of angiogenesis. A hydroxypropyl‐β‐cyclodextrin (HPβCD) formulation of pseudopterosin A (PsA) elicited a 25% increase in cell proliferation (EC50 = 1.34 ×10−8 M) in growth factor depleted HUVEC lines. This constitutes a >200 fold increase in potency over DMSO formulations. We demonstrate that the effect of PsA is mediated through inhibition of adenosine A2B receptors which leads to decreased synthesis of cAMP and that this effect can be reversed with a selective A2 agonist, CV‐1808. In addition we show that PsA can induce protein kinase B (AKT) phosphorylation which has been shown to activate proliferation via the phosphatidylinositol 3‐kinase (PI3K) pathway. Collectively, this indicates that pseudopterosins are promising compounds for adenosine receptor mediated pathologies.