6533b825fe1ef96bd1283277

RESEARCH PRODUCT

Citrus limon-derived nanovesicles inhibit cancer cell proliferation and suppress CML xenograft growth by inducing TRAIL-mediated cell death

Francesca MonteleoneFlores NaselliA. FlugySimona FontanaLaura SaievaStefania RaimondoGiacomo De LeoMaria Antonietta Di BellaGiovanni ZitoMauro MannoRiccardo AlessandroAlessia Lo Dico

subject

MaleProteomicsCitrusCell signalingProgrammed cell deathTime Factorsexosome-like nanovesiclesCell SurvivalCellApoptosisMice SCIDBiologyExosomesTNF-Related Apoptosis-Inducing LigandCitrus limon L.; TRAIL-mediated cell death; cancer; exosome-like nanovesiclesCitrus limon L.Mice Inbred NODCell Line TumorLeukemia Myelogenous Chronic BCR-ABL PositiveHuman Umbilical Vein Endothelial CellsmedicinecancerAnimalsHumansCell ProliferationPlant ProteinsPlants MedicinalPlant ExtractsCell growthCancermedicine.diseaseTRAIL-mediated cell deathAntineoplastic Agents PhytogenicXenograft Model Antitumor AssaysMicrovesiclesTumor BurdenFruit and Vegetable Juicesmedicine.anatomical_structureOncologyApoptosisImmunologyCancer researchNanoparticlesSignal transductionResearch PaperPhytotherapySignal Transduction

description

// Stefania Raimondo 1 , Flores Naselli 1 , Simona Fontana 1 , Francesca Monteleone 1 , Alessia Lo Dico 1 , Laura Saieva 1 , Giovanni Zito 2 , Anna Flugy 1 , Mauro Manno 3 , Maria Antonietta Di Bella 1 , Giacomo De Leo 1 , Riccardo Alessandro 1 1 Dipartimento di Biopatologia e Biotecnologie Mediche, Universita degli Studi di Palermo, sezione di Biologia e Genetica, Palermo, Italy 2 Laboratorio di Ingegneria Tissutale – Piattaforme Innovative per l’Ingegneria Tissutale (PON01–00829), Istituto Ortopedico Rizzoli, Palermo, Italy 3 Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Palermo, Italy Correspondence to: Riccardo Alessandro, e-mail: riccardo.alessandro@unipa.it Keywords: cancer, exosome-like nanovesicles, Citrus limon L., TRAIL-mediated cell death Received: April 03, 2015      Accepted: May 08, 2015      Published: May 18, 2015 ABSTRACT Nanosized vesicles are considered key players in cell to cell communication, thus influencing physiological and pathological processes, including cancer. Nanovesicles have also been found in edible-plants and have shown therapeutic activity in inflammatory bowel diseases; however information on their role in affecting cancer progression is missing. Our study identify for the first time a fraction of vesicles from lemon juice ( Citrus limon L.), obtained as a result of different ultracentrifugation, with density ranging from 1,15 to 1,19 g/ml and specific proteomic profile. By using an in vitro approach, we show that isolated nanovesicles inhibit cancer cell proliferation in different tumor cell lines, by activating a TRAIL-mediated apoptotic cell death. Furthermore, we demonstrate that lemon nanovesicles suppress CML tumor growth in vivo by specifically reaching tumor site and by activating TRAIL-mediated apoptotic cell processes. Overall, this study suggests the possible use of plant-edible nanovesicles as a feasible approach in cancer treatment.

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