The Brominated Compound Aeroplysinin-1 Inhibits Proliferation and the Expression of Key Pro- Inflammatory Molecules in Human Endothelial and Monocyte Cells

Abstract

Aeroplysinin-1 is a brominated antibiotic used by some sponges for defense against bacterial pathogen invasion. Aeroplysinin-1 has a wide spectrum of anti-tumoral action and behaves as a potent anti-angiogenic compound for bovine aortic endothelial cells. In this study, we demonstrate anti-angiogenic effects of aeroplysinin-1 on human endothelial cells. Furthermore, the response of angiogenesis related genes to aeroplysinin-1 treatment was studied in human endothelial cells by using gene arrays. The major changes were observed in thrombospondin 1 (TSP-1) and monocyte chemoattractant protein-1 (MCP-1), both of which were down-regulated. These inhibitory effects of aeroplysinin-1 were confirmed by using independent experimental approaches. To have a deeper insight on the anti-inflammatory effects of aeroplysinin-1 in endothelial cells, cytokine arrays were also used. This experimental approach confirmed effects on MCP-1 and TSP-1 and showed down-regulation of several other cytokines. Western blotting experiments confirmed down-regulation of ELTD1 (EGF, latrophilin and seven transmembrane domain-containing protein 1), interleukin 1α and matrix metalloproteinase 1 (MMP-1). These results along with our observation of a dramatic inhibitory effect of aeroplysinin-1 on cyclooxygenase-2 protein expression levels in endothelial cells and a human monocyte cell line suggest that aeroplysinin-1 could be a novel anti-inflammatory compound with potential pharmacological interest.

Marine Sponge Derived Antiangiogenic Compounds

“…Results of the inhibition of MMP-2 expression after incubation with aeroplysinin-1 were consistently reproduced in HUVEC and other three different human endothelial cells tested (RF-24, HMEC and EVLC-2), irrespective of their origins [129]. Moreover, expression studies suggest that aeroplysinin-1 decreases the expression levels of MMP-1 in endothelial cells.…”

(+)-Aeroplysinin-1 inhibits Akt and Erk pathway signaling selectively in endothelial cells

“…The alkaloid compound aeroplysinin-1, synthesized by several marine sponges and secreted by them as a defensive weapon [1,4,5], exhibit cytostatic and cytotoxic effects on a wide range of both prokaryote and eukaryote cells [1,[4][5][6][7][8][9][10][11]14,17]. A suggested molecular target for the anti-tumor effect of aeroplysinin-1 is the EGFR tyrosine kinase activity.…”

Pleiotropic effects of spongean alkaloids on mechanisms of cell death, cell cycle progression and DNA damage response (DDR) of acute myeloid leukemia (AML) cells

“…For instance, the spongean alkaloids aeroplysinin-1 and aaptamine are reported to have multiple activities useful for cancer treatment. Aeroplysinin-1 (Ap) is known to inhibit EGF receptor signaling [6], is anti-proliferative [7], causes growth arrest and apoptosis in Ehrlich ascites and HeLa tumor cells [8] and, moreover, has anti-angiogenic potency by inducing apoptosis in endothelial cells [9]. Aaptamine (Aa) causes a p53-independent induction of p21 in chronic myeloid leukemia (CML) cells [10].…”