Evidence map›Paper›PMID 39458999›Full record

ArticlePharmaceuticals (Basel, Switzerland)2024

Vesicle-Transported Multidrug Resistance as a Possible Therapeutic Target of Natural Compounds.

Salvatrice Rigogliuso, Alessandra Cusimano, Lucia Condorelli, Manuela Labbozzetta, Gabriella Schiera, Paola Poma, Monica Notarbartolo

Abstract read
In one paragraph

Article in Pharmaceuticals (Basel, Switzerland), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Salvatrice RigogliusoDepartment of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, 90128 Palermo, Italy.ORCID 0000-0002-7783-0075
Alessandra CusimanoDepartment of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, 90128 Palermo, Italy.ORCID 0000-0002-3595-8898
Lucia CondorelliDepartment of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, 90128 Palermo, Italy.
Manuela LabbozzettaDepartment of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, 90128 Palermo, Italy.
Gabriella SchieraDepartment of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, 90128 Palermo, Italy.ORCID 0000-0002-8638-6455
Paola PomaDepartment of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, 90128 Palermo, Italy.
Monica NotarbartoloDepartment of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, 90128 Palermo, Italy.

Funding

PJ_UTILE_2022VQR_Misura_B D15_NotarbartoloProgetto finanziato dall'Unione europea - Next Generation EU- Overcoming transporter-mediated cancer multidrug REsistance by innovative pharmacological And physiCal sTrategies (REACT) 2022X7ESJ3-CUP B53D23020820006
6 · The paper itself

Abstract

BACKGROUND/

objectivesA key role of extracellular vesicles (EVs) is mediating both cell-cell and cell-stroma communication in pathological/physiological conditions. EVs from resistant tumor cells can transport different molecules like P-glycoprotein (P-gp), acting as a shuttle between donor and recipient cells, resulting in a phenotypic change. The aim of our work was to isolate, characterize, and inhibit the release of EVs in two multidrug resistance (MDR) cancer models: MCF-7R (breast cancer cell line) and HL-60R (acute myeloid leukemia cell line).

methodsThe existence of P-gp in EVs from MDR cells was confirmed by Western blotting assays. The characterization of EVs was carried out by evaluating the size using NTA and the presence of specific markers such as CD63, Hsp70 and Syntenin. The ability of HL-60R and MCF-7R to perform horizontal transfer of P-gp via EVs to sensitive cells was assessed using three different methods. The acquisition of resistance and its inhibition in recipient cells was confirmed by MTS 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay.

resultsOur data showed that cell lines (MDR) release P-gp-loaded EVs, unlike sensitive cells. The acquisition of resistance determined by the incorporation of P-gp into the membrane of sensitive cells was confirmed by the reduced cytotoxic activity of doxorubicin. Natural compounds such as curcumin, lupeol, and heptacosane can block vesicular transfer and restore the sensitivity of HL-60 and MCF-7 cells.

conclusionsOur study demonstrates that natural inhibitors able to reverse this mechanism may represent a new therapeutic strategy to limit the propagation of the resistant phenotype.

Indexed as

acute myeloid leukemiabreast cancercancer drug resistanceextracellular vesiclesP-glycoprotein

Identifiers

PMID39458999
PMCPMC11509960

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