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.
Keywords:
Citrus limon L.; TRAIL-mediated cell death; cancer; exosome-like nanovesicles.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents, Phytogenic / isolation & purification
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Antineoplastic Agents, Phytogenic / metabolism
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Antineoplastic Agents, Phytogenic / pharmacology*
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Apoptosis / drug effects*
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Cell Line, Tumor
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Cell Proliferation / drug effects*
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Cell Survival / drug effects
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Citrus* / chemistry
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Exosomes* / chemistry
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Exosomes* / metabolism
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Fruit and Vegetable Juices
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Human Umbilical Vein Endothelial Cells / drug effects
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Human Umbilical Vein Endothelial Cells / metabolism
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Human Umbilical Vein Endothelial Cells / pathology
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Humans
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
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Male
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Mice, Inbred NOD
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Mice, SCID
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Nanoparticles*
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Phytotherapy
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Plant Extracts / isolation & purification
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Plant Extracts / metabolism
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Plant Extracts / pharmacology*
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Plant Proteins / analysis
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Plants, Medicinal
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Proteomics / methods
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Signal Transduction / drug effects
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TNF-Related Apoptosis-Inducing Ligand / metabolism*
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Time Factors
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Tumor Burden / drug effects*
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Xenograft Model Antitumor Assays
Substances
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Antineoplastic Agents, Phytogenic
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Plant Extracts
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Plant Proteins
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human