title: In vitro antiproliferative and antiangiogenic effects of synthetic chalcone analogues.
abstract: As flavonoids, chalcones possess a wide variety of biological activities including anticancer properties. In the present study we have investigated the in vitro antiproliferative and antiangiogenic effects of four synthetic chalcones. E-2-(4'-methoxybenzylidene)-1-benzosuberone (3) was the most active compound with IC(50)=10(-7)mol l(-1) in Jurkat cells. In both Jurkat and HeLa chalcone 3-treated cells we found a significant increase in the proportion of cancer cells in the G(2)/M phase of the cell cycle as well as an increase in cells having sub-G(0)/G(1) DNA content which is considered to be a marker of apoptotic cell death. Apoptosis was also confirmed by annexin V staining and DNA fragmentation. These effects were associated with reduced expression of the anti-apoptotic gene, Bcl-2, and increased expression of the pro-apoptotic gene, Bax. Furthermore, chalcone 3 was selected to evaluate its effect on some angiogenic events. In non-toxic concentrations, chalcone 3 inhibited VEGF-induced migration of human umbilical vein endothelial cells. Moreover, it also decreased secretion of matrix metalloproteinase (mainly MMP-9) and vascular endothelial growth factor (VEGF). In conclusion, the present study has assessed the in vitro antiproliferative/antiangiogenic potential of chalcone 3. This results generate a rationale for in vivo efficacy studies with this compound in preclinical cancer models.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, PJ Safarik University, Kosice, Slovak Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Pilatova
authors.forename: Lenka
authors.initials: L
authors.lastname: Varinska
authors.forename: Pal
authors.initials: P
authors.lastname: Perjesi
authors.forename: Marek
authors.initials: M
authors.lastname: Sarissky
authors.forename: Ladislav
authors.initials: L
authors.lastname: Mirossay
authors.forename: Peter
authors.initials: P
authors.lastname: Solar
authors.forename: Alexander
authors.initials: A
authors.lastname: Ostro
authors.forename: Jan
authors.initials: J
authors.lastname: Mojzis
mesh_terms: D020533:Angiogenesis Inhibitors / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001593:Benzyl Compounds / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D047188:Chalcones / Q000737:chemistry / Q000633:toxicity*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D013729:Terpenes / Q000633:toxicity*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D001593:Benzyl Compounds; D047188:Chalcones; C515537:E-2-(4'-methoxybenzylidene)-benzusuberone; D013729:Terpenes; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9