Cyclic chalcone analogue KRP6 as a potent modulator of cell proliferation: an in vitro study in HUVECs
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In the present investigation a novel series of chalcone analogues were synthesized and evaluated for their anti-proliferative activity in human umbilical vein endothelial cells (HUVECs). Among 14 tested compounds, chalcone analogue (E)-3-(2′-methoxybenzylidene)-4-chromanone (KRP6) exhibited the most potent activity with IC50 19 μM. Moreover, HUVECs exhibited divergent, even opposing concentration-dependent responses to KRP6. This compound was the most potent inhibitor of cell proliferation and extracellular matrix formation (fibronectin and type IV collagen) at higher concentrations (20–50 μM). In contrast, KRP6 stimulated the compensatory increase in proliferative activity including extracellular matrix formation at low concentrations (1, 10 μM). KRP6 concentration-dependently modulated phosphorylation of Akt and mitogen-activated protein kinases such as extracellular signal-regulated kinase-1/-2 and p38 kinase, suggesting that these pathways play a role in the effect mediated by this compound. In addition, we found a selective effect on activated endothelial cells, in particular with resting endothelial cells. In conclusion, KRP6 is a potent modulator of selected steps of the angiogenic process in vitro. Accordingly, further in vivo research should be performed to facilitate its use in clinical practice.
KeywordsAnti-proliferative effect Cyclic chalcone analogue Endothelial cells In vitro
This work was supported by the Slovak Research and Development Agency under contract No. APVV-0325-07, by SEPO-II (ITMS code: 26220120039) and by Charles University (Grant No. PRVOUK 27-1). We would like to thank Tom Billingham for his careful proof-reading of the manuscript.
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