Instytut Biotechnologii / Institute of Biotechnology

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Browsing Instytut Biotechnologii / Institute of Biotechnology by Author "Deręgowska, Anna"

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    Dane do artykułu "Electrospun fiber-based micro- and nano-system for delivery of high concentrated quercetin to cancer cells"
    (Biomaterials Advances, 2023-10-01) Hudecki, Andrzej; Rzeszutek, Iwona; Lewińska, Anna; Warski, Tymon; Baranowska-Korczyc, Anna; Wojnarowska-Nowak, Renata; Betlej, Gabriela; Deręgowska, Anna; Hudecki, Jacek; Łyko-Morawska, Dorota; Likus, Wirginia; Moskal, Aleksandra; Krzemiński, Piotr; Cieślak, Małgorzata; Kęsik-Brodacka, Małgorzata; Kolano-Burian, Aleksandra; Wnuk, Maciej
    The anticancer potential of quercetin (Q), a plant-derived flavonoid, and underlining molecular mechanisms are widely documented in cellular models in vitro. However, biomedical applications of Q are limited due to its low bioavailability and hydrophilicity. In the present study, the electrospinning approach was used to obtain polylactide (PLA) and PLA and polyethylene oxide (PEO)-based micro- and nanofibers containing Q, namely PLA/Q and PLA/PEO/Q, respectively, in a form of non-woven fabrics. The structure and physico-chemical properties of Q-loaded fibers were characterized by scanning electron and atomic force microscopy (SEM and AFM), X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), goniometry and FTIR and Raman spectroscopy. The anticancer action of PLA/Q and PLA/PEO/Q was revealed using two types of cancer and nine cell lines, namely osteosarcoma (MG-63, U-2 OS, SaOS-2 cells) and breast cancer (SK-BR-3, MCF-7, MDA-MB-231, MDA-MB-468, Hs 578T, and BT-20 cells). The anticancer activity of Q-loaded fibers was more pronounced than the action of free Q. PLA/Q and PLA/PEO/Q promoted cell cycle arrest, oxidative stress and apoptotic cell death that was not overcome by heat shock protein (HSP)-mediated adaptive response. PLA/Q and PLA/PEO/Q were biocompatible and safe, as judged by in vitro testing using normal fibroblasts. We postulate that PLA/Q and PLA/PEO/Q with Q releasing activity can be considered as a novel and more efficient micro- and nano-system to deliver Q and eliminate phenotypically different cancer cells.
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    Dane do artykułu "Mutation Status and Glucose Availability Affect the Response to Mitochondria-Targeted Quercetin Derivative in Breast Cancer Cells"
    (Cancers (Basel) MDPI, 2023-11-28) Przybylski, Paweł; Lewińska, Anna; Rzeszutek, Iwona; Błoniarz, Dominika; Moskal, Aleksandra; Betlej, Gabriela; Deręgowska, Anna; Cybularczyk-Cecotka, Martyna ; Szmatoła, Tomasz ; Litwinienko, Grzegorz; Wnuk, Maciej
    Mitochondria, the main cellular power stations, are important modulators of redox-sensitive signaling pathways that may determine cell survival and cell death decisions. As mitochondrial function is essential for tumorigenesis and cancer progression, mitochondrial targeting has been proposed as an attractive anticancer strategy. In the present study, three mitochondria-targeted quercetin derivatives (mitQ3, 5, and 7) were synthesized and tested against six breast cancer cell lines with different mutation and receptor status, namely ER-positive MCF-7, HER2-positive SK-BR-3, and four triple-negative (TNBC) cells, i.e., MDA-MB-231, MDA-MB-468, BT-20, and Hs 578T cells. In general, the mito-quercetin response was modulated by the mutation status. In contrast to unmodified quercetin, 1 µM mitQ7 induced apoptosis in breast cancer cells. In MCF-7 cells, mitQ7-mediated apoptosis was potentiated under glucose-depleted conditions and was accompanied by elevated mitochondrial superoxide production, while AMPK activation-based energetic stress was associated with the alkalization of intracellular milieu and increased levels of NSUN4. Mito-quercetin also eliminated doxorubicin-induced senescent breast cancer cells, which was accompanied by the depolarization of mitochondrial transmembrane potential. Limited glucose availability also sensitized doxorubicin-induced senescent breast cancer cells to apoptosis. In conclusion, we show an increased cytotoxicity of mitochondria-targeted quercetin derivatives compared to unmodified quercetin against breast cancer cells with different mutation status that can be potentiated by modulating glucose availability.
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    Dataset used in research paper entitled “New Mitochondria-Targeted Fisetin Derivative Compromises Mitophagy and Limits Survival of Drug-Induced Senescent Breast Cancer Cells”
    (Journal of Medicinal Chemistry (ACS), 2024-09-25) Rzeszutek, Iwona; Cybularczyk-Cecotka, Martyna; Deręgowska, Anna; Stec, Paulina; Wnuk, Maciej; Kołodziej, Olga; Kałafut, Joanna; Wawruszak, Anna; Witkowski, Wojciech; Litwinienko, Grzegorz; Lewińska, Anna
    Mitochondria are considered as promising targets for cancer treatment. In the present study, triphenyl phosphonium cationic group-conjugated fisetin (mito-fisetin) was synthesized, and its anticancer activity was investigated in several cellular models of estrogen receptor (ER)-positive breast cancer in vitro and in vivo in proliferating and tamoxifen-promoted senescent states. Mito-fisetin, when used at low micromolar concentrations, stimulated the dissipation of mitochondrial membrane potential and oxidative stress, and affected mitochondrial function, resulting in apoptosis induction in senescent breast cancer cells. Mito-fisetin-mediated cytotoxicity was due to increased levels of phosphorylated AMPK, decreased levels of AKT and HSP90, and impaired mitophagic response, as judged by the analysis of the markers of mitophagosome formation. Senescent breast cancer cells were found to be more sensitive to mito-fisetin treatment than proliferating ones. We postulate that mitochondrial targeting in the case of fisetin may be considered as a promising anticancer and senotherapeutic strategy to eliminate drug-resistant senescent breast cancer cells.
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    Glucotoxicity is mediated by cytoplasmic distribution of RAP1 in pancreatic β-cells
    (Elsevier, 2024-03-28) Deręgowska, Anna; Tomaszek, Natalia; Cuch, Patrycja; Kozioł, Katarzyna; Kaniuka, Olga; Sabadashka, Mariya; Bandura, Yurii; Sybirna, Nataliia
    Diabetes mellitus (DM) is a group of chronic metabolic disorders characterized by persistent hyperglycemia. In our study, we analyzed the level and location of RAP1 changes in the development of β-cell dysfunction induced by glucotoxicity. We employed three pancreatic β-cell lines, namely INS-1, 1.2B4, and NIT-1, as well as a streptozotocin-induced diabetes rat model. We demonstrate that after high glucose treatment, RAP1 is increased, probably through induction by AKT, allowing RAP1 to shuttle from the nucleus to the cytoplasm and activate NF-κB signaling. Furthermore, non-enzymatic post-translational modifications of RAP1, such as advanced glycation end products and carbonylation may affect the function of RAP1, such as activation of the NF-κB signaling. Taken together, we showed that RAP1 is a new player in the mechanism of glucotoxicity in pancreatic β-cells.
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    Upregulation of GRP78 is accompanied by decreased antioxidant response and mitophagy promotion in streptozotocin-induced type 1 diabetes in rats - original data
    (Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2024-09-25) Kaniuka, Olena; Deręgowska, Anna; Bandura, Yurii; Sabadashka, Mariya; Chala, Dariya; Kulachkovskyi, Olexandr; Kubis, Hubert; Adamczyk-Grochala, Jagoda; Sybirna, Nataliia
    Endoplasmic reticulum stress, oxidative stress, and mitochondrial dysfunction are interconnected processes involved in the pathogenesis of diabetes mellitus (DM). In the present study, we demonstrate a distinct unfolded protein response (UPR) signaling pathways in two mammalian models of DM: β-TC-6 cell line and streptozotocin induced type 1 diabetes model in rats. However, a feature common to both systems was the upregulation of the GRP78 protein. Moreover, in vivo studies showed the disruption of the antioxidant system and an escalation of mitophagy against the background of a depletion of the level of ATP in pancreatic cells. In conclusion, we suggest that glucotoxic conditions induced GRP78 upregulation, and next cause depletion of the antioxidant pool and disruption of the functioning of antioxidant defense enzymes and in consequence promote mitophagy in pancreatic cells. Therefore, GRP78 may be considered as a potential therapeutic factor in patients with diabetes.