Kolegium Nauk Przyrodniczych / College of Natural Sciences

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Browsing Kolegium Nauk Przyrodniczych / College of Natural Sciences by Author "Błoniarz, Dominika"

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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 "Evaluation of anticancer activity of urotropine surface modified iron oxide nanoparticles using a panel of forty breast cancer cell lines "
    (Taylor & Francis, 2025-02-28) Adamczyk-Grochala, Jagoda; Wnuk, Maciej; Oklejewicz, Bernadetta; Klimczak, Katarzyna; Błoniarz, Dominika; Deręgowska, Anna; Rzeszutek, Iwona; Stec, Paulina; Ciuraszkiewicz, Agnieszka; Kądziołka-Gaweł, Mariola; Łukowiec, Dariusz; Piotrowski, Piotr; Litwinienko, Grzegorz; Radoń, Adrian; Lewińska, Anna
    Urotropine, an antibacterial agent to treat urinary tract bacterial infections, can be also considered as a repurposed drug with formaldehyde-mediated anticancer activity. Recently, we have synthesized urotropine surface modified iron oxide nanoparticles (URO@Fe3O4 NPs) with improved colloidal stability and limited cytotoxicity against human fibroblasts. In the present study, we have investigated URO@Fe3O4 NP-mediated responses in a panel of forty phenotypically different breast cancer cell lines along with three non-cancerous corresponding cell lines. URO@Fe3O4 NPs promoted oxidative stress and FOXO3a-based antioxidant response in breast cancer cells. Elevated levels of GPX4 and decreased levels of ACSL4 in URO@Fe3O4 NP-treated breast cancer cells protected against ferroptotic cell death. On the contrary, URO@Fe3O4 NPs impaired the activity of PERK, a part of unfolded protein response (UPR), especially when the glucose supply was limited, that was accompanied by genetic instability, and apoptotic and/or necrotic cell death in breast cancer cells. In conclusion, this is the first comprehensive analysis of anticancer effects of URO@Fe3O4 NPs against a panel of forty breast cancer cell lines with different receptor status and in glucose replete and deplete conditions. We suggest that presented results might be helpful for designing new nano-based anti-breast cancer strategies.
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    Dataset used in research paper entitled “Design of a Magnetic Nanoplatform Based on CD26 Targeting and HSP90 Inhibition for Apoptosis and Ferroptosis-Mediated Elimination of Senescent Cells”
    (ACS Publications, 2025-01-13) Wnuk, Maciej; Del Sol-Fernández, Susel; Błoniarz, Dominika; Słaby, Julia; Szmatoła, Tomasz; Żebrowski, Michał; Martínez-Vicente, Pablo; Litwinienko, Grzegorz; Moros, María; Lewińska, Anna
    The accumulation of senescent cells, a hallmark of aging and age-related diseases, is also considered as a side effect of anticancer therapies, promoting drug resistance and leading to treatment failure. The use of senolytics, selective inducers of cell death in senescent cells, is a promising pharmacological antiaging and anticancer approach. However, more studies are needed to overcome the limitations of first-generation senolytics by the design of targeted senolytics and nanosenolytics and the validation of their usefulness in biological systems. In the present study, we have designed a nanoplatform composed of iron oxide nanoparticles functionalized with an antibody against a cell surface marker of senescent cells (CD26), and loaded with the senolytic drug HSP90 inhibitor 17-DMAG (MNP@CD26@17D). We have documented its action against oxidative stress-induced senescent human fibroblasts, WI-38 and BJ cells, and anticancer drug-induced senescent cutaneous squamous cell carcinoma A431 cells, demonstrating for the first time that CD26 is a valid marker of senescence in cancer cells. A dual response to MNP@CD26@17D stimulation in senescent cells was revealed, namely, apoptosis-based early response (2 h treatment) and ferroptosis-based late response (24 h treatment). MNP@CD26@17D-mediated ferroptosis might be executed by ferritinophagy as judged by elevated levels of the ferritinophagy marker NCOA4 and a decreased pool of ferritin. As 24 h treatment with MNP@CD26@17D did not induce hemolysis in human erythrocytes in vitro, this newly designed nanoplatform could be considered as an optimal multifunctional tool to target and eliminate senescent cells of skin origin, overcoming their apoptosis resistance.
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    Orginal dataset used to generate the presentation of results in reserach paper entitled "Carbon-Coated Iron Oxide Nanoparticles Promote Reductive Stress-Mediated Cytotoxic Autophagy in Drug-Induced Senescent Breast Cancer Cells"
    (ACS Applied Materials & Interfaces, 2024-03-14) Lewińska, Anna; Radoń, Adrian; Gil, Kacper; Błoniarz, Dominika; Ciuraszkiewicz, Agnieszka; Kubacki, Jerzy; Kądziołka-Gaweł, Mariola; Łukowiec, Dariusz; Gębara, Piotr; Krogul-Sobczak, Agnieszka; Piotrowski, Piotr; Fijałkowska, Oktawia; Wybraniec, Sylwia; Szmatoła, Tomasz; Kolano-Burian, Aleksandra; Wnuk, Maciej
    The surface modification of magnetite nanoparticles (Fe3O4 NPs) is a promising approach to obtaining biocompatible and multifunctional nanoplatforms with numerous applications in biomedicine, for example, to fight cancer. However, little is known about the effects of Fe3O4 NP-associated reductive stress against cancer cells, especially against chemotherapy-induced drug-resistant senescent cancer cells. In the present study, Fe3O4 NPs in situ coated by dextran (Fe3O4@Dex) and glucosamine-based amorphous carbon coating (Fe3O4@aC) with potent reductive activity were characterized and tested against drug-induced senescent breast cancer cells (Hs 578T, BT-20, MDA-MB-468, and MDA-MB-175-VII cells). Fe3O4@aC caused a decrease in reactive oxygen species (ROS) production and an increase in the levels of antioxidant proteins FOXO3a, SOD1, and GPX4 that was accompanied by elevated levels of cell cycle inhibitors (p21, p27, and p57), proinflammatory (NFκB, IL-6, and IL-8) and autophagic (BECN1, LC3B) markers, nucleolar stress, and subsequent apoptotic cell death in etoposide-stimulated senescent breast cancer cells. Fe3O4@aC also promoted reductive stress-mediated cytotoxicity in nonsenescent breast cancer cells. We postulate that Fe3O4 NPs, in addition to their well-established hyperthermia and oxidative stress-mediated anticancer effects, can also be considered, if modified using amorphous carbon coating with reductive activity, as stimulators of reductive stress and cytotoxic effects in both senescent and nonsenescent breast cancer cells with different gene mutation statuses.
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    Surowe dane badawcze do artykułu "Non-targeting siRNA-mediated responses are associated with apoptosis in chemotherapy-induced senescent skin cancer cells"
    (Chemico-Biological Interactions, 2023-01-05) Betlej, Gabriela; Błoniarz, Dominika; Lewińska, Anna; Wnuk, Maciej
    It is widely accepted that siRNA transfection can promote some off-target effects in the genome; however, little is known about how the cells can respond to the presence of non-viral dsRNA. In the present study, non-targeting control siRNA (NTC-siRNA) was used to evaluate its effects on the activity of pathogen and host-derived nucleic acid-associated signaling pathways such as cGAS-STING, RIG-I, MDA5 and NF-κB in A431 skin cancer cells and BJ fibroblasts. NTC-siRNA treatment promoted cytotoxicity in cancer cells. Furthermore, NTC-siRNA-treated doxorubicin-induced senescent cancer cells were more prone to apoptotic cell death compared to untreated doxorubicin-induced senescent cancer cells. NTC-siRNA stimulated the levels of NF-κB, APOBECs, ALY, LRP8 and phosphorylated STING that suggested the involvement of selected components of nucleic acid sensing pathways in NTC-siRNA-mediated cell death response in skin cancer cells. NTC-siRNA-mediated apoptosis in cancer cells was not associated with IFN-β-based pro-inflammatory response and TRDMT1-based adaptive response. In contrast, in NTC-siRNA-treated fibroblasts, an increase in the levels of RIG-I and IFN-β was not accompanied by affected cell viability. We propose that the use of NTC-siRNA in genetic engineering may provoke a number of unexpected effects that should be carefully monitored. In our experimental settings, NTC-siRNA promoted the elimination of doxorubicin-induced senescent cancer cells that may have implications in skin cancer therapies.