Browsing by Author "Litwinienko, Grzegorz"

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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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    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.