Cargando…

Aglianico Grape Seed Semi-Polar Extract Exerts Anticancer Effects by Modulating MDM2 Expression and Metabolic Pathways

Grapevine (Vitis vinifera L.) seeds are rich in polyphenols including proanthocyanidins, molecules with a variety of biological effects including anticancer action. We have previously reported that the grape seed semi-polar extract of Aglianico cultivar (AGS) was able to induce apoptosis and decreas...

Descripción completa

Detalles Bibliográficos
Autores principales: Cuciniello, Rossana, Di Meo, Francesco, Sulli, Maria, Demurtas, Olivia Costantina, Tanori, Mirella, Mancuso, Mariateresa, Villano, Clizia, Aversano, Riccardo, Carputo, Domenico, Baldi, Alfonso, Diretto, Gianfranco, Filosa, Stefania, Crispi, Stefania
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856309/
https://www.ncbi.nlm.nih.gov/pubmed/36672146
http://dx.doi.org/10.3390/cells12020210
_version_ 1784873589863874560
author Cuciniello, Rossana
Di Meo, Francesco
Sulli, Maria
Demurtas, Olivia Costantina
Tanori, Mirella
Mancuso, Mariateresa
Villano, Clizia
Aversano, Riccardo
Carputo, Domenico
Baldi, Alfonso
Diretto, Gianfranco
Filosa, Stefania
Crispi, Stefania
author_facet Cuciniello, Rossana
Di Meo, Francesco
Sulli, Maria
Demurtas, Olivia Costantina
Tanori, Mirella
Mancuso, Mariateresa
Villano, Clizia
Aversano, Riccardo
Carputo, Domenico
Baldi, Alfonso
Diretto, Gianfranco
Filosa, Stefania
Crispi, Stefania
author_sort Cuciniello, Rossana
collection PubMed
description Grapevine (Vitis vinifera L.) seeds are rich in polyphenols including proanthocyanidins, molecules with a variety of biological effects including anticancer action. We have previously reported that the grape seed semi-polar extract of Aglianico cultivar (AGS) was able to induce apoptosis and decrease cancer properties in different mesothelioma cell lines. Concomitantly, this extract resulted in enriched oligomeric proanthocyanidins which might be involved in determining the anticancer activity. Through transcriptomic and metabolomic analyses, we investigated in detail the anticancer pathway induced by AGS. Transcriptomics analysis and functional annotation allowed the identification of the relevant causative genes involved in the apoptotic induction following AGS treatment. Subsequent biological validation strengthened the hypothesis that MDM2 could be the molecular target of AGS and that it could act in both a p53-dependent and independent manner. Finally, AGS significantly inhibited tumor progression in a xenograft mouse model of mesothelioma, confirming also in vivo that MDM2 could act as molecular player responsible for the AGS antitumor effect. Our findings indicated that AGS, exerting a pro-apoptotic effect by hindering MDM2 pathway, could represent a novel source of anticancer molecules.
format Online
Article
Text
id pubmed-9856309
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-98563092023-01-21 Aglianico Grape Seed Semi-Polar Extract Exerts Anticancer Effects by Modulating MDM2 Expression and Metabolic Pathways Cuciniello, Rossana Di Meo, Francesco Sulli, Maria Demurtas, Olivia Costantina Tanori, Mirella Mancuso, Mariateresa Villano, Clizia Aversano, Riccardo Carputo, Domenico Baldi, Alfonso Diretto, Gianfranco Filosa, Stefania Crispi, Stefania Cells Article Grapevine (Vitis vinifera L.) seeds are rich in polyphenols including proanthocyanidins, molecules with a variety of biological effects including anticancer action. We have previously reported that the grape seed semi-polar extract of Aglianico cultivar (AGS) was able to induce apoptosis and decrease cancer properties in different mesothelioma cell lines. Concomitantly, this extract resulted in enriched oligomeric proanthocyanidins which might be involved in determining the anticancer activity. Through transcriptomic and metabolomic analyses, we investigated in detail the anticancer pathway induced by AGS. Transcriptomics analysis and functional annotation allowed the identification of the relevant causative genes involved in the apoptotic induction following AGS treatment. Subsequent biological validation strengthened the hypothesis that MDM2 could be the molecular target of AGS and that it could act in both a p53-dependent and independent manner. Finally, AGS significantly inhibited tumor progression in a xenograft mouse model of mesothelioma, confirming also in vivo that MDM2 could act as molecular player responsible for the AGS antitumor effect. Our findings indicated that AGS, exerting a pro-apoptotic effect by hindering MDM2 pathway, could represent a novel source of anticancer molecules. MDPI 2023-01-04 /pmc/articles/PMC9856309/ /pubmed/36672146 http://dx.doi.org/10.3390/cells12020210 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cuciniello, Rossana
Di Meo, Francesco
Sulli, Maria
Demurtas, Olivia Costantina
Tanori, Mirella
Mancuso, Mariateresa
Villano, Clizia
Aversano, Riccardo
Carputo, Domenico
Baldi, Alfonso
Diretto, Gianfranco
Filosa, Stefania
Crispi, Stefania
Aglianico Grape Seed Semi-Polar Extract Exerts Anticancer Effects by Modulating MDM2 Expression and Metabolic Pathways
title Aglianico Grape Seed Semi-Polar Extract Exerts Anticancer Effects by Modulating MDM2 Expression and Metabolic Pathways
title_full Aglianico Grape Seed Semi-Polar Extract Exerts Anticancer Effects by Modulating MDM2 Expression and Metabolic Pathways
title_fullStr Aglianico Grape Seed Semi-Polar Extract Exerts Anticancer Effects by Modulating MDM2 Expression and Metabolic Pathways
title_full_unstemmed Aglianico Grape Seed Semi-Polar Extract Exerts Anticancer Effects by Modulating MDM2 Expression and Metabolic Pathways
title_short Aglianico Grape Seed Semi-Polar Extract Exerts Anticancer Effects by Modulating MDM2 Expression and Metabolic Pathways
title_sort aglianico grape seed semi-polar extract exerts anticancer effects by modulating mdm2 expression and metabolic pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856309/
https://www.ncbi.nlm.nih.gov/pubmed/36672146
http://dx.doi.org/10.3390/cells12020210
work_keys_str_mv AT cuciniellorossana aglianicograpeseedsemipolarextractexertsanticancereffectsbymodulatingmdm2expressionandmetabolicpathways
AT dimeofrancesco aglianicograpeseedsemipolarextractexertsanticancereffectsbymodulatingmdm2expressionandmetabolicpathways
AT sullimaria aglianicograpeseedsemipolarextractexertsanticancereffectsbymodulatingmdm2expressionandmetabolicpathways
AT demurtasoliviacostantina aglianicograpeseedsemipolarextractexertsanticancereffectsbymodulatingmdm2expressionandmetabolicpathways
AT tanorimirella aglianicograpeseedsemipolarextractexertsanticancereffectsbymodulatingmdm2expressionandmetabolicpathways
AT mancusomariateresa aglianicograpeseedsemipolarextractexertsanticancereffectsbymodulatingmdm2expressionandmetabolicpathways
AT villanoclizia aglianicograpeseedsemipolarextractexertsanticancereffectsbymodulatingmdm2expressionandmetabolicpathways
AT aversanoriccardo aglianicograpeseedsemipolarextractexertsanticancereffectsbymodulatingmdm2expressionandmetabolicpathways
AT carputodomenico aglianicograpeseedsemipolarextractexertsanticancereffectsbymodulatingmdm2expressionandmetabolicpathways
AT baldialfonso aglianicograpeseedsemipolarextractexertsanticancereffectsbymodulatingmdm2expressionandmetabolicpathways
AT direttogianfranco aglianicograpeseedsemipolarextractexertsanticancereffectsbymodulatingmdm2expressionandmetabolicpathways
AT filosastefania aglianicograpeseedsemipolarextractexertsanticancereffectsbymodulatingmdm2expressionandmetabolicpathways
AT crispistefania aglianicograpeseedsemipolarextractexertsanticancereffectsbymodulatingmdm2expressionandmetabolicpathways