title: Citrus limon-derived nanovesicles inhibit cancer cell proliferation and suppress CML xenograft growth by inducing TRAIL-mediated cell death.
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.
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche, Università degli Studi di Palermo, sezione di Biologia e Genetica, Palermo, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Raimondo
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche, Università degli Studi di Palermo, sezione di Biologia e Genetica, Palermo, Italy.
authors.forename: Flores
authors.initials: F
authors.lastname: Naselli
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche, Università degli Studi di Palermo, sezione di Biologia e Genetica, Palermo, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Fontana
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche, Università degli Studi di Palermo, sezione di Biologia e Genetica, Palermo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Monteleone
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche, Università degli Studi di Palermo, sezione di Biologia e Genetica, Palermo, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Lo Dico
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche, Università degli Studi di Palermo, sezione di Biologia e Genetica, Palermo, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Saieva
authors.affiliation: Laboratorio di Ingegneria Tissutale - Piattaforme Innovative per l'Ingegneria Tissutale (PON01-00829), Istituto Ortopedico Rizzoli, Palermo, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zito
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche, Università degli Studi di Palermo, sezione di Biologia e Genetica, Palermo, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Flugy
authors.affiliation: Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Palermo, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Manno
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche, Università degli Studi di Palermo, sezione di Biologia e Genetica, Palermo, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Di Bella
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche, Università degli Studi di Palermo, sezione di Biologia e Genetica, Palermo, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: De Leo
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche, Università degli Studi di Palermo, sezione di Biologia e Genetica, Palermo, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Alessandro
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002957:Citrus / Q000737:chemistry; D055354:Exosomes / Q000737:chemistry / Q000378:metabolism; D000067030:Fruit and Vegetable Juices; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D053758:Nanoparticles; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D010940:Plant Proteins / Q000032:analysis; D010946:Plants, Medicinal; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D010940:Plant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human
keywords: Citrus limon L.; TRAIL-mediated cell death; cancer; exosome-like nanovesicles