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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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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  • Istanbul Atlas University

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