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    Öğe
    Antioxidative Effects of Curcumin on Erastin-Induced Ferroptosis Through GPX4 Signalling
    (MDPI, 2025) Kose, T; Sharp, PA; Latunde-Dada, GO
    Background/Objectives: Pancreatic cancer is a common gastrointestinal cancer with high risk of mortality. Currently, the therapeutic strategies for pancreatic cancers are surgery, chemotherapy, and radiotherapy, none of which are effective treatments. Ferroptosis is a new form of cell death that is iron (Fe)-dependent and characterized by lipid peroxidation, which is a new approach for treatment of pancreatic cancer. Therefore, this study was dedicated to investigating the effect of erastin and Ras-selective lethal small molecule 3 (RLS3) as ferroptosis inducers as well as focusing on the antioxidant effects of two natural products, curcumin and (-)-epigallocatechin-3-gallate (EGCG), against ferroptosis. Methods: PANC1 cells were treated with 20 mu mol/L curcumin or EGCG and then exposed to 20 mu mol/L erastin. Cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay, Reactive Oxygen Species (ROS) were measured by dihydrodichlorofluorescein (H2DCF) cell-permeant probe, Fe levels were determined by inductively coupled plasma mass spectrometry (ICP-MS), and glutathione (GSH), lipid peroxidation, Western blot, and mRNA were assayed with commercially available kits. Results: Curcumin and EGCG enhanced cell viability in erastin-treated PANC1 cells in a dose-and time-dependent manner. Erastin-treated PANC1 cells exhibited the elevated levels of GSH depletion, ROS productions, and lipid peroxidation while curcumin reversed the erastin-induced ferroptotic effects. The treatment of erastin-induced PANC1 cells with curcumin increased the GPX4 mRNA gene and protein levels. Also, curcumin decreased the FTH1 mRNA gene levels as a strong Fe chelator. Conclusions: In conclusion, this study shows that erastin can be potentially a therapeutic strategy for treatment of cancer cells. Additionally, curcumin might play an antioxidant role at the specific concentrations, potentially mitigating ferroptosis in cells.
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    Öğe
    The effect of fortification on in vitro iron and zinc bioavailability in plant-based meat alternatives
    (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2025) Kose, T; de Bie, T; Wang, RZ; Eilander, A; Wanders, A; Sharp, PA
    Plant-based diets are increasingly popular due to their perceived health benefits and positive environmental impact. However, there are concerns that long-term adherence to plant-based diets could result in nutritional deficiencies, especially for minerals found in abundance in animal foods. Therefore, plant-based meat substitutes may be a vehicle for fortification to provide a source of bioavailable minerals. This study investigated the iron (Fe), zinc (Zn) and calcium (Ca) content and bioavailability from unfortified and Fe and/or Zn fortified plant-based mince (PBM) compared with animal mince. Total and bioaccessible mineral levels in animal mince, and PBM were determined using microwave digestion and in vitro simulated gastrointestinal digestion, respectively. Mineral bioavailability was assessed by exposure of Caco-2 cells to the digested food samples and measuring mineral uptake into the cells using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Total phytate levels were measured to calculate the phytic acid:mineral molar ratio (PA:Fe, PA:Zn, PA:Ca) as indication of the mineral bioavailability. Fe bioavailability from animal mince was significantly greater than from unfortified PBM. Fortification of PBM with Fe reduced the PA:Fe molar ratio to below 10, and increased Fe bioavailability compared with the unfortified PBM. Total Fe uptake from fortified PBM was equivalent to that from animal mince. Following fortification of PBM with Zn, the PA:Zn ratio remained high (>14), and bioavailability was not enhanced compared with the unfortified PBM (P > 0.1). This study highlights that Fe-fortified PBM can improve Fe bioavailability and provide similar amounts of Fe compared to beef mince, whereas more research is needed for Zn fortification of PBM. Fortification can be a promising approach to reduce the phytic acid:mineral molar ratio to mitigate the inhibitory effect of PA on mineral bioavailability.