Ex Vivo Anti-Leukemic Effect of Exosome-like Grapefruit-Derived Nanovesicles from Organic Farming—The Potential Role of Ascorbic Acid

Citrus fruits are a natural source of ascorbic acid, and exosome-like nanovesicles obtained from these fruits contain measurable levels of ascorbic acid. We tested the ability of grapefruit-derived extracellular vesicles (EVs) to inhibit the growth of human leukemic cells and leukemic patient-derive...

Full description

Bibliographic Details
Main Authors: Germana Castelli, Mariantonia Logozzi, Davide Mizzoni, Rossella Di Raimo, Annamaria Cerio, Vincenza Dolo, Luca Pasquini, Maria Screnci, Tiziana Ottone, Ugo Testa, Stefano Fais, Elvira Pelosi
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/21/15663
_version_ 1797631835132395520
author Germana Castelli
Mariantonia Logozzi
Davide Mizzoni
Rossella Di Raimo
Annamaria Cerio
Vincenza Dolo
Luca Pasquini
Maria Screnci
Tiziana Ottone
Ugo Testa
Stefano Fais
Elvira Pelosi
author_facet Germana Castelli
Mariantonia Logozzi
Davide Mizzoni
Rossella Di Raimo
Annamaria Cerio
Vincenza Dolo
Luca Pasquini
Maria Screnci
Tiziana Ottone
Ugo Testa
Stefano Fais
Elvira Pelosi
author_sort Germana Castelli
collection DOAJ
description Citrus fruits are a natural source of ascorbic acid, and exosome-like nanovesicles obtained from these fruits contain measurable levels of ascorbic acid. We tested the ability of grapefruit-derived extracellular vesicles (EVs) to inhibit the growth of human leukemic cells and leukemic patient-derived bone marrow blasts. Transmission electron microscopy and nanoparticle tracking analysis (NTA) showed that the obtained EVs were homogeneous exosomes, defined as exosome-like plant-derived nanovesicles (ELPDNVs). The analysis of their content has shown measurable amounts of several molecules with potent antioxidant activity. ELPDNVs showed a time-dependent antiproliferative effect in both U937 and K562 leukemic cell lines, comparable with the effect of high-dosage ascorbic acid (2 mM). This result was confirmed by a clear decrease in the number of AML blasts induced by ELPDNVs, which did not affect the number of normal cells. ELPDNVs increased the ROS levels in both AML blast cells and U937 without affecting ROS storage in normal cells, and this effect was comparable to ascorbic acid (2 mM). With our study, we propose ELPDNVs from grapefruits as a combination/supporting therapy for human leukemias with the aim to improve the effectiveness of the current therapies.
first_indexed 2024-03-11T11:27:58Z
format Article
id doaj.art-01b4b5c9f4e8481b970f441562457cef
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-11T11:27:58Z
publishDate 2023-10-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-01b4b5c9f4e8481b970f441562457cef2023-11-10T15:04:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-10-0124211566310.3390/ijms242115663Ex Vivo Anti-Leukemic Effect of Exosome-like Grapefruit-Derived Nanovesicles from Organic Farming—The Potential Role of Ascorbic AcidGermana Castelli0Mariantonia Logozzi1Davide Mizzoni2Rossella Di Raimo3Annamaria Cerio4Vincenza Dolo5Luca Pasquini6Maria Screnci7Tiziana Ottone8Ugo Testa9Stefano Fais10Elvira Pelosi11Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Clinical Medicine, Public Health, Life and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, ItalyCore Facilities, Istituto Superiore di Sanità, 00161 Rome, ItalyBanca Regionale Sangue Cordone Ombelicale, UOC Immunoematologia e Medicina Trasfusionale, Policlinico Umberto I, 00161 Rome, ItalyDepartment of Biomedicine and Prevention, Tor Vergata University, 00133 Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyCitrus fruits are a natural source of ascorbic acid, and exosome-like nanovesicles obtained from these fruits contain measurable levels of ascorbic acid. We tested the ability of grapefruit-derived extracellular vesicles (EVs) to inhibit the growth of human leukemic cells and leukemic patient-derived bone marrow blasts. Transmission electron microscopy and nanoparticle tracking analysis (NTA) showed that the obtained EVs were homogeneous exosomes, defined as exosome-like plant-derived nanovesicles (ELPDNVs). The analysis of their content has shown measurable amounts of several molecules with potent antioxidant activity. ELPDNVs showed a time-dependent antiproliferative effect in both U937 and K562 leukemic cell lines, comparable with the effect of high-dosage ascorbic acid (2 mM). This result was confirmed by a clear decrease in the number of AML blasts induced by ELPDNVs, which did not affect the number of normal cells. ELPDNVs increased the ROS levels in both AML blast cells and U937 without affecting ROS storage in normal cells, and this effect was comparable to ascorbic acid (2 mM). With our study, we propose ELPDNVs from grapefruits as a combination/supporting therapy for human leukemias with the aim to improve the effectiveness of the current therapies.https://www.mdpi.com/1422-0067/24/21/15663grapefruit nanovesiclesascorbic acid (vitamin C)acute myeloid leukemia (AML)oxidative stress
spellingShingle Germana Castelli
Mariantonia Logozzi
Davide Mizzoni
Rossella Di Raimo
Annamaria Cerio
Vincenza Dolo
Luca Pasquini
Maria Screnci
Tiziana Ottone
Ugo Testa
Stefano Fais
Elvira Pelosi
Ex Vivo Anti-Leukemic Effect of Exosome-like Grapefruit-Derived Nanovesicles from Organic Farming—The Potential Role of Ascorbic Acid
International Journal of Molecular Sciences
grapefruit nanovesicles
ascorbic acid (vitamin C)
acute myeloid leukemia (AML)
oxidative stress
title Ex Vivo Anti-Leukemic Effect of Exosome-like Grapefruit-Derived Nanovesicles from Organic Farming—The Potential Role of Ascorbic Acid
title_full Ex Vivo Anti-Leukemic Effect of Exosome-like Grapefruit-Derived Nanovesicles from Organic Farming—The Potential Role of Ascorbic Acid
title_fullStr Ex Vivo Anti-Leukemic Effect of Exosome-like Grapefruit-Derived Nanovesicles from Organic Farming—The Potential Role of Ascorbic Acid
title_full_unstemmed Ex Vivo Anti-Leukemic Effect of Exosome-like Grapefruit-Derived Nanovesicles from Organic Farming—The Potential Role of Ascorbic Acid
title_short Ex Vivo Anti-Leukemic Effect of Exosome-like Grapefruit-Derived Nanovesicles from Organic Farming—The Potential Role of Ascorbic Acid
title_sort ex vivo anti leukemic effect of exosome like grapefruit derived nanovesicles from organic farming the potential role of ascorbic acid
topic grapefruit nanovesicles
ascorbic acid (vitamin C)
acute myeloid leukemia (AML)
oxidative stress
url https://www.mdpi.com/1422-0067/24/21/15663
work_keys_str_mv AT germanacastelli exvivoantileukemiceffectofexosomelikegrapefruitderivednanovesiclesfromorganicfarmingthepotentialroleofascorbicacid
AT mariantonialogozzi exvivoantileukemiceffectofexosomelikegrapefruitderivednanovesiclesfromorganicfarmingthepotentialroleofascorbicacid
AT davidemizzoni exvivoantileukemiceffectofexosomelikegrapefruitderivednanovesiclesfromorganicfarmingthepotentialroleofascorbicacid
AT rosselladiraimo exvivoantileukemiceffectofexosomelikegrapefruitderivednanovesiclesfromorganicfarmingthepotentialroleofascorbicacid
AT annamariacerio exvivoantileukemiceffectofexosomelikegrapefruitderivednanovesiclesfromorganicfarmingthepotentialroleofascorbicacid
AT vincenzadolo exvivoantileukemiceffectofexosomelikegrapefruitderivednanovesiclesfromorganicfarmingthepotentialroleofascorbicacid
AT lucapasquini exvivoantileukemiceffectofexosomelikegrapefruitderivednanovesiclesfromorganicfarmingthepotentialroleofascorbicacid
AT mariascrenci exvivoantileukemiceffectofexosomelikegrapefruitderivednanovesiclesfromorganicfarmingthepotentialroleofascorbicacid
AT tizianaottone exvivoantileukemiceffectofexosomelikegrapefruitderivednanovesiclesfromorganicfarmingthepotentialroleofascorbicacid
AT ugotesta exvivoantileukemiceffectofexosomelikegrapefruitderivednanovesiclesfromorganicfarmingthepotentialroleofascorbicacid
AT stefanofais exvivoantileukemiceffectofexosomelikegrapefruitderivednanovesiclesfromorganicfarmingthepotentialroleofascorbicacid
AT elvirapelosi exvivoantileukemiceffectofexosomelikegrapefruitderivednanovesiclesfromorganicfarmingthepotentialroleofascorbicacid