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    Effects of somatostatin and vitamin C on the fatty acid profile of breast cancer cell membranes
    (Bentham Science Publ Ltd, 2019) Hanikoğlu, Ayşegüll; Küçüksayan, Ertan; Hanikoğlu, Ferhat; Özben, Tomris; Menounou, Georgia; Sansone, Anna; Ferreri, Carla
    Background: Vitamin C (Vit C) is an important physiological antioxidant with growing applications in cancer. Somatostatin (SST) is a natural peptide with growth inhibitory effect in several mammary cancer models. Objective: The combined effects of SST and Vit C supplementation have never been studied in breast cancer cells so far. Methods: We used MCF-7 and MDA-MB231 breast cancer cells incubated with SST for 24h, in the absence and presence of Vit C, at their EC 50 concentrations, to evaluate membrane fatty acid-profiles together with the follow-up of EGFR and MAPK signaling pathways. Results: The two cell lines gave different membrane reorganization: in MCF-7 cells, decrease of omega-6 linoleic acid and increase of omega-3 fatty acids (Fas) occurred after SST and SST+Vit C incubations, the latter also showing significant increases in MUFA, docosapentaenoic acid and mono-trans arachidonic acid levels. In MDA-MB231 cells, SST+Vit C incubation induced significant membrane remodeling with an increase of stearic acid and mono-trans-linoleic acid isomer, diminution of omega-6 linoleic, arachidonic acid and omega-3 (docosapentaenoic and docosadienoic acids). Distinct signaling pathways in these cell lines were studied: in MCF-7 cells, incubations with SST and Vit C, alone or in combination significantly decreased EGFR and MAPK signaling, whereas in MDA-MB231 cells, SST and Vit C incubations, alone or combined, decreased pP44/42 MAPK levels, and increased EGFR levels. Conclusion: Our results showed that SST and Vit C can be combined to induce membrane fatty acid changes, including lipid isomerization through a specific free radical-driven process, influencing signaling pathways.
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    Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes
    (Canadian Science Publishing, 2020) Hanikoğlu, Ayşegül; Küçüksayan, Ertan; Hanikoğlu, Ferhat; Özben, Tomris; Menounou, Georgia; Sansone, Anna; Ferreri, Carla
    Breast cancer is a worldwide commonly found malignancy in women and effective treatment is regarded as a huge clinical challenge even in the presence of several treatment options. Extensive literature is available demonstrating polyphenols as phytopharmaceutical anticancer agents. Among the polyphenols, quercetin and curcumin have been reported to have a strong potential against breast cancer. However, so far, no comprehensive study has been performed to demonstrate the anticarcinogenic effects of curcumin, quercetin, and their combinations with somatostatin on the fatty acid profile of breast cancer cell membranes. We used MCF-7 and MDA-MB231 breast cancer cells incubated with curcumin and quercetin for 24 h, in the absence and presence of somatostatin, at their EC50 concentrations to evaluate membrane fatty acid based functional lipidomics together with the followup of EGFR and MAPK signaling pathways. The two cell lines gave different membrane free fatty acid reorganization. In MCF-7 cells, the following changes were observed: an increase of omega 6 linoleic acid in the cells incubated with somatostatin + quercetin and quercetin and a decrease of omega 3 acids in the cells incubated with somatostatin + curcumin compared to somatostatin and significant increases of monounsaturated fatty acid (MUFA), mono-trans arachidonic acid levels and docosapentaenoic acid for the cells incubated with somatostatin + quercetin compared to the control cells. In MDA-MB231 cells, incubations with curcumin, quercetin, and somatostatin + quercetin induced the most significant membrane remodeling with the increase of stearic acid, diminution of omega 6 linoleic, arachidonic acids, and omega 3 (docosapentaenoic and docosahexaenoic acids). Distinct signaling pathway changes were found for these cell lines. In MCF-7 cells, separate or combined incubations with somatostatin and quercetin, significantly decreased EGFR and incubation with curcumin decreased MAPK signaling. In MDA-MB231 cells, incubation with curcumin decreased AKT1 and p-AKT1 (Thr308) levels. Incubation with curcumin and quercetin decreased the EGFR levels. Our results showed that cytostatic and antioxidant treatments can be combined to induce membrane fatty acid changes, including lipid isomerization as specific free radical driven process, and to influence signaling pathways. This study aimed to contribute to the literature on these antioxidants in the treatment of breast cancer to clarify the effects and mechanisms in combination with somatostatin.
  • Küçük Resim
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    Sapienic Acid Metabolism Influences Membrane Plasticity and Protein Signaling in Breast Cancer Cell Lines
    (2022) Küçüksayan, Ertan; Sansone, Anna; Chatgilialoglu, Chryssostomos; Özben, Tomris; Tekeli, Demet; Talibova, Günel; Ferreri, Carla
    Abstract: The importance of sapienic acid (6c-16:1), a monounsaturated fatty acid of the n-10 family formed from palmitic acid by delta-6 desaturase, and of its metabolism to 8c-18:1 and sebaleic acid (5c,8c-18:2) has been recently assessed in cancer. Data are lacking on the association between signaling cascades and exposure to sapienic acid comparing cell lines of the same cancer type. We used 50 µM sapienic acid supplementation, a non-toxic concentration, to cultivate MCF-7 and 2 triplenegative breast cancer cells (TNBC), MDA-MB-231 and BT-20. We followed up for three hours regarding membrane fatty acid remodeling by fatty acid-based membrane lipidome analysis and expression/phosphorylation of EGFR (epithelial growth factor receptor), mTOR (mammalian target of rapamycin) and AKT (protein kinase B) by Western blotting as an oncogenic signaling cascade. Results evidenced consistent differences among the three cell lines in the metabolism of n-10 fatty acids and signaling. Here, a new scenario is proposed for the role of sapienic acid: one based on changes in membrane composition and properties, and the other based on changes in expression/activation of growth factors and signaling cascades. This knowledge can indicate additional players and synergies in breast cancer cell metabolism, inspiring translational applications of tailored membrane lipid strategies to assist pharmacological interventions.