Przeglądanie według Autor "Wnuk, Maciej"

Aktualnie wyświetlane 1 - 2 z 2

Electrospun fiber-based micro- and nano-system for delivery of high concentrated quercetin to cancer cells
(2023-10) 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.
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.