title: Tomato cystine-knot miniproteins possessing anti-angiogenic activity exhibit in vitro gastrointestinal stability, intestinal absorption and resistance to food industrial processing.
abstract: The cystine-knot miniproteins present in tomato fruit (TCMPs) have been shown to exert anti-angiogenic effects by inhibiting endothelial cell migration and to display resistance to gastrointestinal proteolytic attack. To better define the pharmacological potential of TCMPs, their oral bioavailability and their resistance to industrial processing must be assessed. To explore the intestinal transport of TCMPs we used the differentiated Caco-2 cells model. After 24h incubation, 37.73±9.34% of TCMPs crossed the epithelium, without altering the integrity of the cell layer. To assess the effects of the industrial processing on the biochemical features and the biological activity of TCMPs, we developed a method for purifying the proteins from tomato paste. The tomato-paste purified TCMPs retained the resistance to gastrointestinal digestion and the inhibitory activity towards endothelial cell migration. Our previous and present results collectively demonstrate that TCMPs possess interesting features for drug development.
authors.affiliation: Department of Biotechnology, University of Verona, Strada Le Grazie 15, 37134 Verona Italy; Department of Medicine, Section of Internal Medicine, University of Verona, P.le L.A. Scuro 10, 37134 Verona Italy. Electronic address: davide.treggiari@univr.it.
authors.forename: Davide
authors.initials: D
authors.lastname: Treggiari
authors.affiliation: Department of Biotechnology, University of Verona, Strada Le Grazie 15, 37134 Verona Italy. Electronic address: gianni.zoccatelli@univr.it.
authors.forename: Gianni
authors.initials: G
authors.lastname: Zoccatelli
authors.affiliation: Department of Biotechnology, University of Verona, Strada Le Grazie 15, 37134 Verona Italy. Electronic address: roberto.chignola@univr.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Chignola
authors.affiliation: Department of Biotechnology, University of Verona, Strada Le Grazie 15, 37134 Verona Italy. Electronic address: barbara.molesini@univr.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Molesini
authors.affiliation: Department of Medicine, Section of Internal Medicine, University of Verona, P.le L.A. Scuro 10, 37134 Verona Italy. Electronic address: pietro.minuz@univr.it.
authors.forename: Pietro
authors.initials: P
authors.lastname: Minuz
authors.affiliation: Department of Biotechnology, University of Verona, Strada Le Grazie 15, 37134 Verona Italy. Electronic address: tiziana.pandolfini@univr.it.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Pandolfini
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D057771:Cystine-Knot Miniproteins / Q000008:administration & dosage / Q000627:therapeutic use*; D005511:Food Handling; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D018551:Solanum lycopersicum / Q000737:chemistry*
chemical_list: D020533:Angiogenesis Inhibitors; D057771:Cystine-Knot Miniproteins
keywords: Cystine-knot miniproteins; Endothelial cell migration; Gastrointestinal digestion; Intestinal transport; Tomato paste