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

Our plain-English summary of Aglianico Grape Seed Semi-Polar Extract Exerts Anticancer Effects by Modulating MDM2 Expression and Metabolic Pathways, by R. Cuciniello, F. Di Meo, M. Sulli, et al (Cells, 2023).

The study

• Authors: R. Cuciniello, F. Di Meo, M. Sulli, O.C. Demurtas, M. Tanori, M. Mancuso, C. Villano, R. Aversano, D. Carputo, A. Baldi, G. Diretto, S. Filosa, S. Crispi
• Journal: Cells
• Published: 2023;12(2)
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

In plain English

This laboratory study tested an extract from Aglianico grape seeds (AGS). It did not study asbestos exposure or patients. The authors measured gene activity in treated MSTO mesothelioma cells, checked key genes in three mesothelioma lines, and measured cell chemistry in MSTO, breast and prostate cancer cells. In MSTO cells, 665 genes were turned up and 397 turned down. Computer analysis pointed to a gene called MDM2. In all three mesothelioma lines, MDM2 and JUN fell and p53 rose after treatment. In breast (MDA) and prostate (PC3) cancer cells lacking working p53, the higher dose cut cell viability by about 50%, with no effect seen in matching non-cancer cells. Apoptosis (programmed cell death) rose by about 52% in MDA and about 23% in PC3 cells. Lactic acid fell in MSTO, MDA and PC3 cells. In mice with implanted mesothelioma tumors (8 treated, 6 controls), four weeks of injections reduced final tumor mass by 40%, and treated mice stayed healthy. The authors concluded that the extract triggered apoptosis by lowering MDM2 and altering glucose metabolism, and could be a source of new anticancer molecules.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study: experiments on human cancer cell lines (gene expression, protein and metabolite analyses) plus a mouse xenograft (implanted tumor) experiment
• Who was studied: Human mesothelioma cell lines MSTO-211H (MSTO), NCI-H2452 (NCI) and Ist-Mes2 (Mes2), with whole-genome expression profiling in MSTO only; breast cancer cell line MDA-MB-231 and prostate cancer cell line PC-3, with non-tumor cell lines MCF10A and PNT2; metabolite analysis in MSTO, PC3 and MDA cells; 6-week-old NU/NU CD1 male mice implanted with MSTO cells (control n = 6, AGS-treated n = 8)
• Exposure: Not asbestos. The exposure was Aglianico grape seed semi-polar extract (AGS), given to cells at 150 or 350 µg/mL in two doses over 24 + 24 h, and to mice at 100 mg/kg by intraperitoneal injection three times a week for four weeks
• Main results:
  • In MSTO mesothelioma cells treated with AGS, 665 genes were upregulated and 397 downregulated
  • In all three mesothelioma cell lines (MSTO, NCI, Mes2), AGS treatment lowered JUN and MDM2 expression and raised p53
  • In breast (MDA) and prostate (PC3) cancer cells, 350 µg/mL AGS reduced cell viability by about 50% compared to untreated cells
  • No effect on viability was seen in the non-tumor cell lines MCF10A and PNT2
  • Compared to untreated cells, apoptosis increased by about 52% in MDA cells and about 23% in PC3 cells
  • Metabolite analysis was done in MSTO, PC3 and MDA cells; lactic acid was reduced in all of these AGS-treated cell lines
  • In AGS-treated mice, final tumor mass was reduced by 40% compared with untreated controls (p < 0.0001)
  • AGS-treated mice remained healthy through 28 days
  • Tumors from AGS-treated mice showed a higher apoptotic index (p < 0.0004) and decreased MDM2 expression (p < 0.0001) than controls
• The authors' conclusion: The authors concluded that apoptosis induced by AGS occurred through MDM2 downregulation and concomitant modulation of glucose metabolism, and that AGS could be viewed as a natural source of novel anticancer drug molecules

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Apoptosis, Mesothelioma.

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