title: Cucurbitacin B purified from Ecballium elaterium (L.) A. Rich from Tunisia inhibits α5β1 integrin-mediated adhesion, migration, proliferation of human glioblastoma cell line and angiogenesis.
abstract: Integrins are essential protagonists in the complex multistep process of cancer progression and are thus attractive targets for the development of anticancer agents. Cucurbitacin B, a triterpenoid purified from the leaves of Tunisian Ecballium elaterium exhibited an anticancer effect and displayed anti-integrin activity on human glioblastoma U87 cells, without being cytotoxic at concentrations up to 500nM. Here we show that cucurbitacin B affected the adhesion and migration of U87 cells to fibronectin in a dose-dependent manner with IC50 values of 86.2nM and 84.6nM, respectively. Time-lapse videomicroscopy showed that cucurbitacin B significantly reduced U87 cells motility and affected directional persistence. Cucurbitacin B also inhibited proliferation with IC50 value of 70.1nM using Crystal Violet assay. Moreover, cucurbitacin B efficiently inhibited in vitro human microvascular endothelial cells (HMEC) angiogenesis with concentration up to 10nM. Interestingly, we demonstrate for the first time that this effect was specifically mediated by α5β1 integrins. These findings reveal a novel mechanism of action for cucurbitacin B, which displays a potential interest as a specific anti-integrin drug.
authors.affiliation: Laboratoire des Substances Naturelles (LR10INRAP02), Institut National de Recherche et d'Analyse Physico-chimique, Sidi Thabet, 2020 Ariana, Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Touihri-Barakati
authors.affiliation: Laboratoire des Substances Naturelles (LR10INRAP02), Institut National de Recherche et d'Analyse Physico-chimique, Sidi Thabet, 2020 Ariana, Tunisia.
authors.forename: Olfa
authors.initials: O
authors.lastname: Kallech-Ziri
authors.affiliation: Laboratoire des Substances Naturelles (LR10INRAP02), Institut National de Recherche et d'Analyse Physico-chimique, Sidi Thabet, 2020 Ariana, Tunisia.
authors.forename: Wiem
authors.initials: W
authors.lastname: Ayadi
authors.affiliation: Aix-Marseille Université, INSERM, Centre de Recherche en Oncologie Biologique et Oncopharmacologie (CRO2) UMR 911, Faculté de Pharmacie, 13385 Marseille, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Kovacic
authors.affiliation: Faculté des Sciences de Tunis, Campus Universitaire, Tunis El Manar, 1000 Tunis, Tunisia.
authors.forename: Belgacem
authors.initials: B
authors.lastname: Hanchi
authors.affiliation: Laboratoire des Substances Naturelles (LR10INRAP02), Institut National de Recherche et d'Analyse Physico-chimique, Sidi Thabet, 2020 Ariana, Tunisia.
authors.forename: Karim
authors.initials: K
authors.lastname: Hosni
authors.affiliation: Aix-Marseille Université, INSERM, Centre de Recherche en Oncologie Biologique et Oncopharmacologie (CRO2) UMR 911, Faculté de Pharmacie, 13385 Marseille, France. Electronic address: jose.luis@univ-amu.fr.
authors.forename: José
authors.initials: J
authors.lastname: Luis
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D019662:Cucurbitaceae / Q000737:chemistry*; D005909:Glioblastoma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D039081:Integrin alpha5beta1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D014315:Triterpenes / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D039081:Integrin alpha5beta1; D014315:Triterpenes; C041246:cucurbitacin B
keywords: Angiogenesis; Cancer; Cucurbitacin; Glioblastoma; Integrin; Migration