title: Effect of selected flavones on cancer and endothelial cells.
abstract: In our study we used quercetin (3,3 ,4 ,5,7-pentahydroxyflavone) as the reference standard to compare antiproliferative and antiangiogenic effects of chrysin (5,7-dihydroxyflavone) and 3-hydroxyflavone. Our data indicates that chrysin and 3-hydroxyflavone showed significantly higher cytotoxic effect than reference standard quercetin. These tested agents significantly decreased cell survival with the efficacy of 65-85% at the concentration 100 micromol/l for HUVEC, lung carcinoma and leukemic cells being the most sensitive. Cell cycle analysis indicates that quercetin and 3-hydroxyflavone might affect the cell cycle of Jurkat cells by a similar or the same mechanism of action which lead to G2/M arrest as well as to an increase in sub-G0/G1 fraction. Treatment of Jurkat cells with chrysin resulted only increase in the fraction of cells with sub-G0/G1 DNA content, which is considered to be a marker of apoptotic cell death. Apoptosis was confirmed by DNA fragmentation and by staining with annexin V. All three tested flavones inhibited endothelial cell migration after 24 h of incubation at a concentration 100 micromol/l. At a lower concentration (10 micromol/l) only quercetin significantly inhibited migration of endothelial cells. Furthermore, in our experiments decreased secretion of matrix metalloproteinases (MMP-2 and MMP-9) was observed after a 72 h treatment with quercetin. No decrease in secretion of MMP-2 and MMP-9 was seen after chrysin and 3-hydroxyflavone treatment. On the other hand, our results showed that none of three flavonoids blocked microcapillary tube formation. Further studies are necessary to investigate the mechanism of action and to find out the relationship between the structure, character and position of substituents of natural substances and their biological activities.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, P. J. Safárik University, Kosice, Slovakia.
authors.forename: Martina
authors.initials: M
authors.lastname: Pilátová
authors.forename: Viktória
authors.initials: V
authors.lastname: Stupáková
authors.forename: Lenka
authors.initials: L
authors.lastname: Varinská
authors.forename: Marek
authors.initials: M
authors.lastname: Sarisský
authors.forename: Ladislav
authors.initials: L
authors.lastname: Mirossay
authors.forename: Andrej
authors.initials: A
authors.lastname: Mirossay
authors.forename: Peter
authors.initials: P
authors.lastname: Gál
authors.forename: Vladimír
authors.initials: V
authors.lastname: Kraus
authors.forename: Katarína
authors.initials: K
authors.lastname: Dianisková
authors.forename: Ján
authors.initials: J
authors.lastname: Mojzis
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D047309:Flavones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011794:Quercetin / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D047309:Flavones; D005419:Flavonoids; C043561:chrysin; D011794:Quercetin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C041477:3-hydroxyflavone