{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T19:45:01Z","timestamp":1784663101157,"version":"3.55.0"},"reference-count":59,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CNR project NUTR-AGE","award":["FOE-2019"],"award-info":[{"award-number":["FOE-2019"]}]},{"name":"CNR project NUTR-AGE","award":["DSB.AD004.271"],"award-info":[{"award-number":["DSB.AD004.271"]}]},{"name":"CNR project NUTR-AGE","award":["ARS01_00783"],"award-info":[{"award-number":["ARS01_00783"]}]},{"name":"CNR project NUTR-AGE","award":["CN00000022"],"award-info":[{"award-number":["CN00000022"]}]},{"name":"University and Research project ALIFUN","award":["FOE-2019"],"award-info":[{"award-number":["FOE-2019"]}]},{"name":"University and Research project ALIFUN","award":["DSB.AD004.271"],"award-info":[{"award-number":["DSB.AD004.271"]}]},{"name":"University and Research project ALIFUN","award":["ARS01_00783"],"award-info":[{"award-number":["ARS01_00783"]}]},{"name":"University and Research project ALIFUN","award":["CN00000022"],"award-info":[{"award-number":["CN00000022"]}]},{"name":"European Union Next-GenerationEU","award":["FOE-2019"],"award-info":[{"award-number":["FOE-2019"]}]},{"name":"European Union Next-GenerationEU","award":["DSB.AD004.271"],"award-info":[{"award-number":["DSB.AD004.271"]}]},{"name":"European Union Next-GenerationEU","award":["ARS01_00783"],"award-info":[{"award-number":["ARS01_00783"]}]},{"name":"European Union Next-GenerationEU","award":["CN00000022"],"award-info":[{"award-number":["CN00000022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells12020210","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T04:08:07Z","timestamp":1672805287000},"page":"210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Aglianico Grape Seed Semi-Polar Extract Exerts Anticancer Effects by Modulating MDM2 Expression and Metabolic Pathways"],"prefix":"10.3390","volume":"12","author":[{"given":"Rossana","family":"Cuciniello","sequence":"first","affiliation":[{"name":"Institute of Biosciences and BioResources-UOS Naples CNR, Via P. Castellino 111, 80131 Naples, Italy"},{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Di Meo","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and BioResources-UOS Naples CNR, Via P. Castellino 111, 80131 Naples, Italy"},{"name":"Department of Medicine, Indiana University School of Medicine, 975 W Walnut Street, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6875-2546","authenticated-orcid":false,"given":"Maria","family":"Sulli","sequence":"additional","affiliation":[{"name":"Division of Biotechnology and Agroindustry, Biotechnology Laboratory, ENEA, Casaccia Research Center, Via Anguillarese 301, 00123 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3344-5754","authenticated-orcid":false,"given":"Olivia Costantina","family":"Demurtas","sequence":"additional","affiliation":[{"name":"Division of Biotechnology and Agroindustry, Biotechnology Laboratory, ENEA, Casaccia Research Center, Via Anguillarese 301, 00123 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8020-2224","authenticated-orcid":false,"given":"Mirella","family":"Tanori","sequence":"additional","affiliation":[{"name":"Division of Health Protection Technologies, ENEA, Casaccia Research Center, Via Anguillarese 301, 00123 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0912-9287","authenticated-orcid":false,"given":"Mariateresa","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Division of Health Protection Technologies, ENEA, Casaccia Research Center, Via Anguillarese 301, 00123 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9407-0146","authenticated-orcid":false,"given":"Clizia","family":"Villano","sequence":"additional","affiliation":[{"name":"Department of Agricultural Sciences, University of Naples Federico II, Via Universit\u00e0 100, 80055 Portici, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Aversano","sequence":"additional","affiliation":[{"name":"Department of Agricultural Sciences, University of Naples Federico II, Via Universit\u00e0 100, 80055 Portici, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1735-9338","authenticated-orcid":false,"given":"Domenico","family":"Carputo","sequence":"additional","affiliation":[{"name":"Department of Agricultural Sciences, University of Naples Federico II, Via Universit\u00e0 100, 80055 Portici, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8693-3842","authenticated-orcid":false,"given":"Alfonso","family":"Baldi","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and BioResources-UOS Naples CNR, Via P. Castellino 111, 80131 Naples, Italy"},{"name":"Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania \u201cL. Vanvitelli\u201d, 81055 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1441-0233","authenticated-orcid":false,"given":"Gianfranco","family":"Diretto","sequence":"additional","affiliation":[{"name":"Division of Biotechnology and Agroindustry, Biotechnology Laboratory, ENEA, Casaccia Research Center, Via Anguillarese 301, 00123 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2896-3362","authenticated-orcid":false,"given":"Stefania","family":"Filosa","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and BioResources-UOS Naples CNR, Via P. 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