title: Cyclic chalcone analogue KRP6 as a potent modulator of cell proliferation: an in vitro study in HUVECs.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, P. J. Safarik University, Kosice, Slovak Republic, lenka.ivanova@student.upjs.sk.
authors.forename: Lenka
authors.initials: L
authors.lastname: Ivanova
authors.forename: Lenka
authors.initials: L
authors.lastname: Varinska
authors.forename: Martina
authors.initials: M
authors.lastname: Pilatova
authors.forename: Peter
authors.initials: P
authors.lastname: Gal
authors.forename: Peter
authors.initials: P
authors.lastname: Solar
authors.forename: Pal
authors.initials: P
authors.lastname: Perjesi
authors.forename: Karel
authors.initials: K
authors.lastname: Smetana
authors.forename: Alexander
authors.initials: A
authors.lastname: Ostro
authors.forename: Jan
authors.initials: J
authors.lastname: Mojzis
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002599:Chalcone