title: Dietary gallic acid and anthocyanin cytotoxicity on human fibrosarcoma HT1080 cells. A study on the mode of action.
abstract: Gallic acid and anthocyanins are abundant plant food bioactives present in many fruits and vegetables, being especially important in the composition of berries. Gallic acid has been shown to possess cytotoxic properties in several cancer cell lines and to inhibit carcinogenesis in animal models. However, its mechanism of action is not yet fully understood. The aim of this study was to elucidate whether the observed inhibitory activity of gallic acid against gelatinases corresponds to its cytotoxic activity in HT1080 cells and to determine if anthocyanins could exhibit a similar behavior. Gallic acid and delphinidin-3-glucoside have shown selective cytotoxicity towards HT1080 cells. Further analysis by a migration and invasion assay showed anti-invasive activities of gallic acid, delphinidin and pelargonidin-3-glucosides. Zymographic analysis demonstrated the inhibitory activity of gallic acid at the level of secreted and activated gelatinases. Moreover, gallic acid inhibited MMP-2 and MMP-9 proteolytic activity with very similar potency. NMR and molecular modelling experiments confirmed the interaction of gallic acid with MMP-2, and suggested that it takes place within the catalytic center. In this work we give some new experimental data supporting the role of these compounds in the inhibition of metalloproteases as the mechanism for their cytotoxic activity against fibrosarcoma.
authors.affiliation: Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad CEU San Pablo, Urbanización Monteprincipe, 28668 Madrid, Spain.
authors.forename: Kamila
authors.initials: K
authors.lastname: Filipiak
authors.forename: Maria
authors.initials: M
authors.lastname: Hidalgo
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Silvan
authors.forename: Benjamin
authors.initials: B
authors.lastname: Fabre
authors.forename: Rodrigo J
authors.initials: RJ
authors.lastname: Carbajo
authors.forename: Antonio
authors.initials: A
authors.lastname: Pineda-Lucena
authors.forename: Ana
authors.initials: A
authors.lastname: Ramos
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Pascual-Teresa
authors.forename: Sonia
authors.initials: S
authors.lastname: de Pascual-Teresa
mesh_terms: D000872:Anthocyanins / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019587:Dietary Supplements / Q000032:analysis; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D005707:Gallic Acid / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D008954:Models, Biological; D008958:Models, Molecular
chemical_list: D000872:Anthocyanins; D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D005707:Gallic Acid; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9