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Plant-derived extracellular nanovesicles: a promising biomedical approach for effective targeting of triple negative breast cancer cells

Title: Plant-derived extracellular nanovesicles: a promising biomedical approach for effective targeting of triple negative breast cancer cells
Authors: Cui L.; Perini G.; De Spirito M.; Papi M.
Contributors: Cui, Lishan; Perini, Giordano; Augello, A.; Palmieri, V.; De Spirito, Marco; Papi, Massimiliano
Publisher Information: Frontiers Media SA
Publication Year: 2024
Collection: Università Cattolica del Sacro Cuore: PubliCatt
Subject Terms: Citrus limon L; extracellular nanovesicles; MPAK/ERK; PI3K/AKT; plant-derived extracellular vesicles; triple negative breast cancer; Settore PHYS-06/A - Fisica per le scienze della vita; l'ambiente e i beni culturali
Description: Introduction: Triple negative breast cancer (TNBC), a highly aggressive subtype accounting for 15–20% of all breast cancer cases, faces limited treatment options often accompanied by severe side effects. In recent years, natural extracellular nanovesicles derived from plants have emerged as promising candidates for cancer therapy, given their safety profile marked by non-immunogenicity and absence of inflammatory responses. Nevertheless, the potential anti-cancer effects of Citrus limon L.-derived extracellular nanovesicles (CLENs) for breast cancer treatment is still unexplored. Methods: In this study, we investigated the anti-cancer effects of CLENs on two TNBC cell lines (4T1 and HCC-1806 cells) under growth conditions in 2D and 3D culture environments. The cellular uptake efficiency of CLENs and their internalization mechanism were evaluated in both cells using confocal microscopy. Thereafter, we assessed the effect of different concentrations of CLENs on cell viability over time using a dual approach of Calcein-AM PI live-dead assay and CellTiter-Glo bioluminescence assay. We also examined the influence of CLENs on the migratory and evasion abilities of TNBC cells through wound healing and 3D Matrigel drop evasion assays. Furthermore, Western blot analysis was employed to investigate the effects of CLENs on the phosphorylation levels of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and extracellular signal- regulated kinase (ERK) expression. Results: We found that CLENs were internalized by the cells via endocytosis, leading to decreased cell viability, in a dose- and time-dependent manner. Additionally, the migration and evasion abilities of TNBC cells were significantly inhibited under exposed to 40 and 80μg/mL CLENs. Furthermore, down-regulated expression levels of phosphorylated phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK), suggesting that the inhibition of cancer cell proliferation, migration, and evasion is driven by the ...
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/38952670; info:eu-repo/semantics/altIdentifier/wos/WOS:001259635900001; volume:12; issue:1390708; firstpage:01; lastpage:N/A; numberofpages:N/A; issueyear:2024; journal:FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY; https://hdl.handle.net/10807/313004
DOI: 10.3389/fbioe.2024.1390708
Availability: https://hdl.handle.net/10807/313004; https://doi.org/10.3389/fbioe.2024.1390708
Rights: info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.D87EFA88
Database: BASE