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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.

SUBMITTER: Raimondo S

PROVIDER: S-EPMC4637302 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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

Raimondo Stefania S Naselli Flores F Fontana Simona S Monteleone Francesca F Lo Dico Alessia A Saieva Laura L Zito Giovanni G Flugy Anna A Manno Mauro M Di Bella Maria Antonietta MA De Leo Giacomo G Alessandro Riccardo R

Oncotarget 20150801 23

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 ...[more]

PMID: 26098775

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Project description:BackgroundCitrus yellow vein clearing virus (CYVCV) is the causative agent of citrus yellow vein clearing disease, and poses a serious threat to the lemon industry in Asia. The common symptoms of CYVCV-infected lemon plants are leaf crinkling, leaf chlorotic mottling, and yellow vein clearing. However, the molecular mechanisms underlying CYVCV-citrus interaction that responsible for symptom occurrence is still unclarified. In this study, RNA-seq was performed to analyze the gene expression patterns of 'Eureka' lemon (Citrus limon Burm. f.) plants in response to CYVCV infection.ResultsThere were 3691 differentially expressed genes (DEGs) identified by comparison between mock and CYVCV-infected lemon plants through RNA-seq. Bioinformatics analyses revealed that these DEGs were components of different pathways involved in phenylpropanoid biosynthesis, brassinosteroid biosynthesis, flavonoid biosynthesis and photosynthesis. Among these, the DEGs related to phytohormone metabolism and photosynthesis pathways were further enriched and analyzed. This study showed that different phytohormone-related genes had different responses toward CYVCV infection, however almost all of the photosynthesis-related DEGs were down-regulated in the CYVCV-infected lemon plants. The obtained RNA-seq data were validated by RT-qPCR using 12 randomly chosen genes, and the results of mRNA expression analysis were consistent with those of RNA-seq.ConclusionsThe phytohormone biosynthesis, signaling and photosynthesis-related genes of lemon plants were probably involved in systemic infection and symptom occurrence of CYVCV. Notably, CYVCV infection had regulatory effects on the biosynthesis and signaling of phytohormone, which likely improve systemic infection of CYVCV. Additionally, CYVCV infection could cause structural changes in chloroplast and inhibition of photosynthesis pathway, which probably contribute to the appearance of leaf chlorotic mottling and yellow vein clearing in CYVCV-infected lemon plants. This study illustrates the dynamic nature of the citrus-CYVCV interaction at the transcriptome level and provides new insights into the molecular mechanism underlying the pathogenesis of CYVCV in lemon plants.

Dataset Information

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

Publications

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

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