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In Vitro Effects of an Olive Polyphenol-Bromelain Formulation on U87MG Glioblastoma Cells: Viability, Cell-Cycle Distribution, Cytokine Release, and Total Antioxidant Capacity.

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Title: In Vitro Effects of an Olive Polyphenol-Bromelain Formulation on U87MG Glioblastoma Cells: Viability, Cell-Cycle Distribution, Cytokine Release, and Total Antioxidant Capacity.
Authors: Ciraci E; Department of Biochemistry, Faculty of Pharmacy, Biruni University, Zeytinburnu, 34010 Istanbul, Türkiye.; Biruni Advanced Technology Application and Research Center (BAMER), Biruni University, 34015 Istanbul, Türkiye., Elgun T; Biruni Advanced Technology Application and Research Center (BAMER), Biruni University, 34015 Istanbul, Türkiye.; Department of Medical Biology, Faculty of Medicine, Biruni University, Zeytinburnu, 34015 Istanbul, Türkiye., Oltulu YM; Biruni Advanced Technology Application and Research Center (BAMER), Biruni University, 34015 Istanbul, Türkiye.; Department of Medical Biology, Faculty of Medicine, Biruni University, Zeytinburnu, 34015 Istanbul, Türkiye., Arslan HI; Biruni Advanced Technology Application and Research Center (BAMER), Biruni University, 34015 Istanbul, Türkiye., Yurttas AG; Department of Biochemistry, Faculty of Medicine, Istanbul Atlas University, 34408 Istanbul, Türkiye., Gundogan GI; Biruni Advanced Technology Application and Research Center (BAMER), Biruni University, 34015 Istanbul, Türkiye.; Department of Histology and Embryology, Faculty of Medicine, Biruni University, 34015 Istanbul, Türkiye., Uzun L; Department of Chemistry, Faculty of Science, Hacettepe University, 06800 Ankara, Türkiye., Emekdas G; Turk Kan Vakfi, 34718 Istanbul, Türkiye.
Source: Molecules (Basel, Switzerland) [Molecules] 2026 Sep 20; Vol. 31 (18). Date of Electronic Publication: 2026 Sep 20.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE
Imprint Name(s): Original Publication: Basel, Switzerland : MDPI, c1995-
MeSH Terms: Polyphenols*/pharmacology , Polyphenols*/chemistry , Antioxidants*/pharmacology , Antioxidants*/chemistry , Glioblastoma*/metabolism , Glioblastoma*/drug therapy , Glioblastoma*/pathology , Olea*/chemistry , Cytokines*/metabolism, Cell Survival/drug effects ; Cell Cycle/drug effects ; Humans ; Cell Line, Tumor ; Tandem Mass Spectrometry
Abstract: Background: Glioblastoma (GBM) remains difficult to treat, and natural bioactive formulations are being explored as experimental modifiers of tumor-associated cellular processes. This study examined a fixed-ratio olive polyphenol-bromelain formulation in U87MG cells and performed targeted phenolic characterization of its olive-derived component. Methods: Seven phenolics were quantified by LC-MS/MS. U87MG cells were exposed to the formulation or a bromelain comparator. The MTT metabolic signal, DNA-content cell-cycle distribution, IL-6, IL-10, and extracellular total antioxidant capacity (TAC) were assessed. Results: The total quantified phenolics were 483.22 mg/kg, with oleocanthal, oleuropein, and 3,4-DHPEA-EDA predominating. The formulation reduced the MTT signal more than bromelain at lower and intermediate concentrations, although the response became non-monotonic at higher concentrations. Combination-treated cells showed greater G0/G1 accumulation. Culture supernatants showed lower IL-6 and higher IL-10 and TAC relative to untreated controls. Conclusions: The formulation was associated with changes in metabolic activity, cell-cycle distribution, and extracellular cytokine/redox readouts in U87MG cells. Because no polyphenol-only arm, direct cell-death assay, complete replicate-level inferential analysis, or non-tumoral comparator was available, the findings are descriptive and do not establish synergy, cytotoxicity, mechanism, tumor selectivity, or therapeutic efficacy.
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Neuro Oncol. 2025 Nov 1;27(11):2751-2788. (PMID: 40827022)
NPJ Precis Oncol. 2024 Oct 23;8(1):241. (PMID: 39443641)
Food Sci Nutr. 2025 Sep 18;13(9):e70976. (PMID: 40979569)
Anticancer Res. 2020 Oct;40(10):5427-5436. (PMID: 32988864)
Front Oncol. 2023 Jan 09;12:1068778. (PMID: 36698404)
PLoS One. 2019 Jan 18;14(1):e0210274. (PMID: 30657763)
Semin Cancer Biol. 2016 Oct;40-41:82-99. (PMID: 27117759)
Int J Mol Sci. 2025 Nov 01;26(21):. (PMID: 41226697)
Radiology. 2022 Sep;304(3):494-508. (PMID: 35880978)
JCO Oncol Pract. 2023 Apr;19(4):180-189. (PMID: 36638331)
Neoplasia. 2001 Nov-Dec;3(6):469-79. (PMID: 11774029)
Cell Mol Immunol. 2024 Dec;21(12):1354-1375. (PMID: 39406966)
Nutrients. 2024 Jun 28;16(13):. (PMID: 38999808)
PLoS One. 2010 Apr 16;5(4):e10202. (PMID: 20419137)
Expert Rev Mol Med. 2021 Dec 02;23:e20. (PMID: 34852856)
PLoS One. 2011;6(6):e20849. (PMID: 21695150)
Clin Cancer Res. 2019 Jun 15;25(12):3643-3657. (PMID: 30824583)
Food Funct. 2023 Sep 19;14(18):8101-8128. (PMID: 37650738)
Cytokine Growth Factor Rev. 2025 Oct;85:26-42. (PMID: 39893129)
Mol Carcinog. 2012 Mar;51(3):231-43. (PMID: 21432909)
Molecules. 2020 Nov 14;25(22):. (PMID: 33202681)
Pharmacogn Mag. 2015 Apr-Jun;11(42):404-9. (PMID: 25829782)
Cancer Res. 2010 Jan 15;70(2):440-6. (PMID: 20068163)
Curr Issues Mol Biol. 2025 Aug 18;47(8):. (PMID: 40864821)
Cancer Res. 2026 Jul 15;86(14):3570-3587. (PMID: 41974019)
Neuro Oncol. 2021 Aug 2;23(8):1231-1251. (PMID: 34185076)
Contributed Indexing: Keywords: G0/G1 accumulation; IL-10; IL-6; U87MG; bromelain; cell-cycle distribution; glioblastoma; olive polyphenols; total antioxidant capacity
Substance Nomenclature: 0 (Polyphenols)
0 (Antioxidants)
0 (Cytokines)
Entry Date(s): Date Created: 20260926 Date Completed: 20260926 Latest Revision: 20260929
Update Code: 20260929
PubMed Central ID: PMC13610031
DOI: 10.3390/molecules31183334
PMID: 42796617
Database: MEDLINE
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  Data: In Vitro Effects of an Olive Polyphenol-Bromelain Formulation on U87MG Glioblastoma Cells: Viability, Cell-Cycle Distribution, Cytokine Release, and Total Antioxidant Capacity.
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  Data: <searchLink fieldCode="AU" term="%22Ciraci+E%22">Ciraci E</searchLink>; Department of Biochemistry, Faculty of Pharmacy, Biruni University, Zeytinburnu, 34010 Istanbul, Türkiye.; Biruni Advanced Technology Application and Research Center (BAMER), Biruni University, 34015 Istanbul, Türkiye.<br /><searchLink fieldCode="AU" term="%22Elgun+T%22">Elgun T</searchLink>; Biruni Advanced Technology Application and Research Center (BAMER), Biruni University, 34015 Istanbul, Türkiye.; Department of Medical Biology, Faculty of Medicine, Biruni University, Zeytinburnu, 34015 Istanbul, Türkiye.<br /><searchLink fieldCode="AU" term="%22Oltulu+YM%22">Oltulu YM</searchLink>; Biruni Advanced Technology Application and Research Center (BAMER), Biruni University, 34015 Istanbul, Türkiye.; Department of Medical Biology, Faculty of Medicine, Biruni University, Zeytinburnu, 34015 Istanbul, Türkiye.<br /><searchLink fieldCode="AU" term="%22Arslan+HI%22">Arslan HI</searchLink>; Biruni Advanced Technology Application and Research Center (BAMER), Biruni University, 34015 Istanbul, Türkiye.<br /><searchLink fieldCode="AU" term="%22Yurttas+AG%22">Yurttas AG</searchLink>; Department of Biochemistry, Faculty of Medicine, Istanbul Atlas University, 34408 Istanbul, Türkiye.<br /><searchLink fieldCode="AU" term="%22Gundogan+GI%22">Gundogan GI</searchLink>; Biruni Advanced Technology Application and Research Center (BAMER), Biruni University, 34015 Istanbul, Türkiye.; Department of Histology and Embryology, Faculty of Medicine, Biruni University, 34015 Istanbul, Türkiye.<br /><searchLink fieldCode="AU" term="%22Uzun+L%22">Uzun L</searchLink>; Department of Chemistry, Faculty of Science, Hacettepe University, 06800 Ankara, Türkiye.<br /><searchLink fieldCode="AU" term="%22Emekdas+G%22">Emekdas G</searchLink>; Turk Kan Vakfi, 34718 Istanbul, Türkiye.
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  Data: <searchLink fieldCode="JN" term="%22100964009%22">Molecules (Basel, Switzerland)</searchLink> [Molecules] 2026 Sep 20; Vol. 31 (18). <i>Date of Electronic Publication: </i>2026 Sep 20.
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  Data: <searchLink fieldCode="MM" term="%22Polyphenols%22">Polyphenols*</searchLink>/<searchLink fieldCode="MM" term="%22Polyphenols+pharmacology%22">pharmacology</searchLink> <br /><searchLink fieldCode="MM" term="%22Polyphenols%22">Polyphenols*</searchLink>/<searchLink fieldCode="MM" term="%22Polyphenols+chemistry%22">chemistry</searchLink> <br /><searchLink fieldCode="MM" term="%22Antioxidants%22">Antioxidants*</searchLink>/<searchLink fieldCode="MM" term="%22Antioxidants+pharmacology%22">pharmacology</searchLink> <br /><searchLink fieldCode="MM" term="%22Antioxidants%22">Antioxidants*</searchLink>/<searchLink fieldCode="MM" term="%22Antioxidants+chemistry%22">chemistry</searchLink> <br /><searchLink fieldCode="MM" term="%22Glioblastoma%22">Glioblastoma*</searchLink>/<searchLink fieldCode="MM" term="%22Glioblastoma+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Glioblastoma%22">Glioblastoma*</searchLink>/<searchLink fieldCode="MM" term="%22Glioblastoma+drug+therapy%22">drug therapy</searchLink> <br /><searchLink fieldCode="MM" term="%22Glioblastoma%22">Glioblastoma*</searchLink>/<searchLink fieldCode="MM" term="%22Glioblastoma+pathology%22">pathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Olea%22">Olea*</searchLink>/<searchLink fieldCode="MM" term="%22Olea+chemistry%22">chemistry</searchLink> <br /><searchLink fieldCode="MM" term="%22Cytokines%22">Cytokines*</searchLink>/<searchLink fieldCode="MM" term="%22Cytokines+metabolism%22">metabolism</searchLink><br /><searchLink fieldCode="MH" term="%22Cell+Survival%22">Cell Survival</searchLink>/<searchLink fieldCode="MH" term="%22Cell+Survival+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Cell+Cycle%22">Cell Cycle</searchLink>/<searchLink fieldCode="MH" term="%22Cell+Cycle+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Cell+Line%2C+Tumor%22">Cell Line, Tumor</searchLink> ; <searchLink fieldCode="MH" term="%22Tandem+Mass+Spectrometry%22">Tandem Mass Spectrometry</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: Glioblastoma (GBM) remains difficult to treat, and natural bioactive formulations are being explored as experimental modifiers of tumor-associated cellular processes. This study examined a fixed-ratio olive polyphenol-bromelain formulation in U87MG cells and performed targeted phenolic characterization of its olive-derived component. Methods: Seven phenolics were quantified by LC-MS/MS. U87MG cells were exposed to the formulation or a bromelain comparator. The MTT metabolic signal, DNA-content cell-cycle distribution, IL-6, IL-10, and extracellular total antioxidant capacity (TAC) were assessed. Results: The total quantified phenolics were 483.22 mg/kg, with oleocanthal, oleuropein, and 3,4-DHPEA-EDA predominating. The formulation reduced the MTT signal more than bromelain at lower and intermediate concentrations, although the response became non-monotonic at higher concentrations. Combination-treated cells showed greater G0/G1 accumulation. Culture supernatants showed lower IL-6 and higher IL-10 and TAC relative to untreated controls. Conclusions: The formulation was associated with changes in metabolic activity, cell-cycle distribution, and extracellular cytokine/redox readouts in U87MG cells. Because no polyphenol-only arm, direct cell-death assay, complete replicate-level inferential analysis, or non-tumoral comparator was available, the findings are descriptive and do not establish synergy, cytotoxicity, mechanism, tumor selectivity, or therapeutic efficacy.
– Name: Ref
  Label: References
  Group: RefInfo
  Data: Nat Commun. 2025 Nov 19;16(1):10151. (PMID: <searchLink fieldCode="PM" term="%2241258298%22">41258298)</searchLink><br />Front Cell Dev Biol. 2022 Sep 12;10:1011435. (PMID: <searchLink fieldCode="PM" term="%2236172282%22">36172282)</searchLink><br />Crit Rev Food Sci Nutr. 2002;42(3):209-21. (PMID: <searchLink fieldCode="PM" term="%2212058980%22">12058980)</searchLink><br />Nat Med. 2018 May;24(5):541-550. (PMID: <searchLink fieldCode="PM" term="%2229686425%22">29686425)</searchLink><br />Neuro Oncol. 2025 Nov 1;27(11):2751-2788. (PMID: <searchLink fieldCode="PM" term="%2240827022%22">40827022)</searchLink><br />NPJ Precis Oncol. 2024 Oct 23;8(1):241. (PMID: <searchLink fieldCode="PM" term="%2239443641%22">39443641)</searchLink><br />Food Sci Nutr. 2025 Sep 18;13(9):e70976. (PMID: <searchLink fieldCode="PM" term="%2240979569%22">40979569)</searchLink><br />Anticancer Res. 2020 Oct;40(10):5427-5436. (PMID: <searchLink fieldCode="PM" term="%2232988864%22">32988864)</searchLink><br />Front Oncol. 2023 Jan 09;12:1068778. (PMID: <searchLink fieldCode="PM" term="%2236698404%22">36698404)</searchLink><br />PLoS One. 2019 Jan 18;14(1):e0210274. (PMID: <searchLink fieldCode="PM" term="%2230657763%22">30657763)</searchLink><br />Semin Cancer Biol. 2016 Oct;40-41:82-99. (PMID: <searchLink fieldCode="PM" term="%2227117759%22">27117759)</searchLink><br />Int J Mol Sci. 2025 Nov 01;26(21):. (PMID: <searchLink fieldCode="PM" term="%2241226697%22">41226697)</searchLink><br />Radiology. 2022 Sep;304(3):494-508. (PMID: <searchLink fieldCode="PM" term="%2235880978%22">35880978)</searchLink><br />JCO Oncol Pract. 2023 Apr;19(4):180-189. (PMID: <searchLink fieldCode="PM" term="%2236638331%22">36638331)</searchLink><br />Neoplasia. 2001 Nov-Dec;3(6):469-79. (PMID: <searchLink fieldCode="PM" term="%2211774029%22">11774029)</searchLink><br />Cell Mol Immunol. 2024 Dec;21(12):1354-1375. (PMID: <searchLink fieldCode="PM" term="%2239406966%22">39406966)</searchLink><br />Nutrients. 2024 Jun 28;16(13):. (PMID: <searchLink fieldCode="PM" term="%2238999808%22">38999808)</searchLink><br />PLoS One. 2010 Apr 16;5(4):e10202. (PMID: <searchLink fieldCode="PM" term="%2220419137%22">20419137)</searchLink><br />Expert Rev Mol Med. 2021 Dec 02;23:e20. (PMID: <searchLink fieldCode="PM" term="%2234852856%22">34852856)</searchLink><br />PLoS One. 2011;6(6):e20849. (PMID: <searchLink fieldCode="PM" term="%2221695150%22">21695150)</searchLink><br />Clin Cancer Res. 2019 Jun 15;25(12):3643-3657. (PMID: <searchLink fieldCode="PM" term="%2230824583%22">30824583)</searchLink><br />Food Funct. 2023 Sep 19;14(18):8101-8128. (PMID: <searchLink fieldCode="PM" term="%2237650738%22">37650738)</searchLink><br />Cytokine Growth Factor Rev. 2025 Oct;85:26-42. (PMID: <searchLink fieldCode="PM" term="%2239893129%22">39893129)</searchLink><br />Mol Carcinog. 2012 Mar;51(3):231-43. (PMID: <searchLink fieldCode="PM" term="%2221432909%22">21432909)</searchLink><br />Molecules. 2020 Nov 14;25(22):. (PMID: <searchLink fieldCode="PM" term="%2233202681%22">33202681)</searchLink><br />Pharmacogn Mag. 2015 Apr-Jun;11(42):404-9. (PMID: <searchLink fieldCode="PM" term="%2225829782%22">25829782)</searchLink><br />Cancer Res. 2010 Jan 15;70(2):440-6. (PMID: <searchLink fieldCode="PM" term="%2220068163%22">20068163)</searchLink><br />Curr Issues Mol Biol. 2025 Aug 18;47(8):. (PMID: <searchLink fieldCode="PM" term="%2240864821%22">40864821)</searchLink><br />Cancer Res. 2026 Jul 15;86(14):3570-3587. (PMID: <searchLink fieldCode="PM" term="%2241974019%22">41974019)</searchLink><br />Neuro Oncol. 2021 Aug 2;23(8):1231-1251. (PMID: <searchLink fieldCode="PM" term="%2234185076%22">34185076)</searchLink>
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  Data: <i>Keywords: </i>G0/G1 accumulation; IL-10; IL-6; U87MG; bromelain; cell-cycle distribution; glioblastoma; olive polyphenols; total antioxidant capacity
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        Value: 10.3390/molecules31183334
    Languages:
      – Code: eng
        Text: English
    Subjects:
      – SubjectFull: Cell Survival drug effects
        Type: general
      – SubjectFull: Cell Cycle drug effects
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Cell Line, Tumor
        Type: general
      – SubjectFull: Tandem Mass Spectrometry
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      – SubjectFull: Polyphenols pharmacology
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      – SubjectFull: Polyphenols chemistry
        Type: general
      – SubjectFull: Antioxidants pharmacology
        Type: general
      – SubjectFull: Antioxidants chemistry
        Type: general
      – SubjectFull: Glioblastoma metabolism
        Type: general
      – SubjectFull: Glioblastoma drug therapy
        Type: general
      – SubjectFull: Glioblastoma pathology
        Type: general
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      – SubjectFull: Cytokines metabolism
        Type: general
    Titles:
      – TitleFull: In Vitro Effects of an Olive Polyphenol-Bromelain Formulation on U87MG Glioblastoma Cells: Viability, Cell-Cycle Distribution, Cytokine Release, and Total Antioxidant Capacity.
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