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

Oncotarget. 2015 Aug 14;6(23):19514-27. doi: 10.18632/oncotarget.4004.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / metabolism
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Citrus* / chemistry
  • Exosomes* / chemistry
  • Exosomes* / metabolism
  • Fruit and Vegetable Juices
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells / pathology
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Male
  • Mice, Inbred NOD
  • Mice, SCID
  • Nanoparticles*
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / metabolism
  • Plant Extracts / pharmacology*
  • Plant Proteins / analysis
  • Plants, Medicinal
  • Proteomics / methods
  • Signal Transduction / drug effects
  • TNF-Related Apoptosis-Inducing Ligand / metabolism*
  • Time Factors
  • Tumor Burden / drug effects*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • Plant Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human