Cyclic chalcone analogue KRP6 as a potent modulator of cell proliferation: An in vitro study in HUVECs

Lenka Ivanova, Lenka Varinska, Martina Pilatova, Peter Gal, Peter Solar, Pal Perjesi, Karel Smetana, Alexander Ostro, Jan Mojzis

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4571-4580
Number of pages10
JournalMolecular Biology Reports
Volume40
Issue number7
DOIs
Publication statusPublished - Jul 2013

    Fingerprint

Keywords

  • Anti-proliferative effect
  • Cyclic chalcone analogue
  • Endothelial cells
  • In vitro

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Ivanova, L., Varinska, L., Pilatova, M., Gal, P., Solar, P., Perjesi, P., Smetana, K., Ostro, A., & Mojzis, J. (2013). Cyclic chalcone analogue KRP6 as a potent modulator of cell proliferation: An in vitro study in HUVECs. Molecular Biology Reports, 40(7), 4571-4580. https://doi.org/10.1007/s11033-013-2547-x