dr hab. Ewa Augustin
Zatrudnienie
- Profesor uczelni w Katedra Technologii Leków i Biochemii
Publikacje
Filtry
wszystkich: 68
Katalog Publikacji
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Preparation and characterization of genipin cross-linked porous chitosan–collagen–gelatin scaffolds using chitosan–CO2 solution
PublikacjaNovel porous scaffolds composed of chitosan, collagen and gelatin were prepared by the multistep procedure involving final freeze-drying and characterized. To eliminate the need for residual acid removal from the material after drying, carbon dioxide saturation process was used for chitosan blend formulation. The use of CO2 for chitosan dissolution made the scaffold preparation process more reproducible and economically sustainable....
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Inhibition of T-type calcium channel disrupts Akt signaling and promotes apoptosis in glioblastoma cells.
PublikacjaGlioblastoma multiforme (GBM) are brain tumors that are exceptionally resitant to both radio- and chemotherapy regimens and novel approaches to treatment are needed. T-type calcium channels are one type of low voltage-gated channel (LVCC) involved in embryonic cell proliferation and differentiation; however they are often over-expressed in tumors, including GBM. In this study, we found that inhibition of T-type Ca channels in GBM...
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The role of glucuronidation in drug resistance
PublikacjaThe final therapeutic effect of a drug candidate, which is directed to a specific molecular target strongly depends on its absorption, distribution, metabolism and excretion (ADME). The disruption of at least one element of ADME may result in serious drug resistance. In this work we described the role of one element of this resistance: phase II metabolism with UDP-glucuronosyltransferases (UGTs). UGT function is the transformation...
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Sequential induction of mitotic catastrophe followed by apoptosis in human leukemia MOLT4 cells by imidazoacridinone C-1311
PublikacjaWykazano, że pochodna imidazoakrydonu C-1311 indukuje zahamowanie progresji komórek MOLT4 w fazie G2M cyklu życiowego. Podwyższona ekspresja fosfoepitopu MPM-2 przy jednoczesnym zaniku ufosforylowanej formy Tyr15-cdc2 wskazywała, iż komórki początkowo zablokowane w fazie G2 przechodziły do mitozy. Jednocześnie na skutek nieprawidłowego przebiegu mitozy komórki ulegały katastrofie mitotycznej. Analiza biochenicznych markerów apoptozy...
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Induction of G2/M phase arrest and apoptosis of human leukemia cells by potent antitumor triazoloacridinone C-1305
PublikacjaWykazaliśmy, że pochodna triazoloakrydonu C-1305 w stężeniach biologicznie istotnych indukuje blok cyklu komórkowego w fazie G2/M i apoptozę w komórkach białaczek ludzkich MOLT4 i HL60. Zjawisko apoptozy zostało określone na podstawie charakterystycznych zmian morfologicznych jak i biochemicznych tj. fragmentacji DNA, aktywacji kaspazy 3, cięcia PARP, spadku potencjału mitochondrialnego i ATP oraz eksternalizacji fosfatydyloseryny.
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Stable and degradable microgels linked with cystine for storing and environmentally triggered release of drugs
PublikacjaEnvironmentally sensitive, degradable microgels based on poly(N-isopropylacrylamide) (pNIPA) crosslinked with the diacryloyl derivative of cystine (BISS) were synthesized by applying surfactant-free emulsion polymerization. pNIPA contributed the sensitivity to temperature to the microgels and the cross-linker made them degradable and sensitive to pH. The morphology of the microgels was investigated by using scanning and transmission...
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Improved cytotoxicity and preserved level of cell death induced in colon cancer cells by doxorubicin after its conjugation with iron-oxide magnetic nanoparticles
PublikacjaA promising strategy for overcoming the problem of limited efficacy in antitumor drug delivery and in drug release is the use of a nanoparticle-conjugated drug. Doxorubicin (Dox) anticancer chemotherapeutics has been widely studied in this respect, because of severe cardiotoxic side effects. Here, we investigated the cytotoxic effects, the uptake process, the changes in cell cycle progression and the cell death processes in the...
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New Unsymmetrical Bisacridine Derivatives Noncovalently Attached to Quaternary Quantum Dots Improve Cancer Therapy by Enhancing Cytotoxicity toward Cancer Cells and Protecting Normal Cells
PublikacjaThe use of nanoparticles for the controlled drug delivery to cells has emerged as a good alternative to traditional systemic delivery. Quantum dots (QDs) offer potentially invaluable societal benefits such as drug targeting and in vivo biomedical imaging. In contrast, QDs may also pose risks to human health and the environment under certain conditions. Here, we demonstrated that unique combination of nanocrystals core components...
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DNA-damaging imidazoacridinone C-1311 induces autophagy followed by irreversible growth arrest and senescence in human lung cancer cells
PublikacjaImidazoacridinone 5-diethylaminoethylamino-8-hydroxyimidazoacridinone (C-1311) is an antitumor inhibitor of topoisomerase II and FMS-like tyrosine kinase 3 receptor. In this study, we describe the unique sequence of cellular responses to C-1311 in human non-small cell lung cancer (NSCLC) cell lines, A549 and H460. In A549 cells, C-1311 (IC80 = 0.08 µM) induced G1 and G2/M arrests, whereas H460 cells (IC80 = 0.051 µM) accumulated...
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Design, synthesis and high antitumor potential of new unsymmetrical bisacridine derivatives towards human solid tumors, specifically pancreatic cancers and their unique ability to stabilize DNA G-quadruplexes
PublikacjaNew promising unsymmetrical bisacridine derivatives (UAs), have been developed. Three groupsincluding 36 compounds were synthesized by the condensation of 4-nitro or 4-methylacridinone, imi-dazoacridinone and triazoloacridinone derivatives with 1-nitroacridine compounds linked with anaminoalkyl chain. Cytotoxicity screening revealed the high potency of these compounds against severaltumor cell lines. Particularly, imidazoacridinone-1-nitroacridine...
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Quantum Dots as a Good Carriers of Unsymmetrical Bisacridines for Modulating Cellular Uptake and the Biological Response in Lung and Colon Cancer Cells
PublikacjaNanotechnology-based drug delivery provides a promising area for improving the efficacy of cancer treatments. Therefore, we investigate the potential of using quantum dots (QDs) as drug carriers for antitumor unsymmetrical bisacridine derivatives (UAs) to cancer cells. We examine the influence of QD–UA hybrids on the cellular uptake, internalization (Confocal Laser Scanning Microscope), and the biological response (flow cytometry...
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Obtaining and Characterization of the PLA/Chitosan Foams with Antimicrobial Properties Achieved by the Emulsification Combined with the Dissolution of Chitosan by CO2 Saturation
PublikacjaA new method of obtaining functional foam material has been proposed. The materials were created by mixing the poly lactic acid (PLA) solution in chloroform, chitosan (CS) dissolved in water saturated with CO2 and polyethylene glycol (PEG), and freeze-dried for removal of the solvents. The composite foams were characterized for their structural (SEM, FT-IR, density, porosity), thermal (DSC), functional (hardness, elasticity, swelling...
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Stable nanoconjugates of transferrin with alloyed quaternary nanocrystals Ag–In–Zn–S as a biological entity for tumor recognition
PublikacjaOne way to limit the negative effects of anti-tumor drugs on healthy cells is targeted therapy employing functionalized drug carriers. Here we present a biocompatible and stable nanoconjugate of transferrin anchored to Ag-In-Zn-S quantum dots modified with 11-mercaptoundecanoic acid (Tf-QD) as a drug carrier versus typical anticancer drug, doxorubicin. Detailed investigations of Tf-QD nanoconjugates without and with doxorubicin...
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Foliate-Targeting Quantum Dots-β-Cyclodextrin Nanocarrier for Efficient Delivery of Unsymmetrical Bisacridines to Lung and Prostate Cancer Cells
PublikacjaTargeted drug delivery by nanocarriers molecules can increase the efficiency of cancer treatment. One of the targeting ligands is folic acid (FA), which has a high affinity for the folic acid receptors, which are overexpressed in many cancers. Herein, we describe the preparation of the nanoconjugates containing quantum dots (QDs) and β-cyclodextrin (β-CD) with foliate-targeting properties for the delivery of anticancer compound...
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Metabolic transformation of antitumor acridinone C-1305 but not C-1311 via selective cellular expression of UGT1A10 increases cytotoxic response: implications for clinical use.
PublikacjaThe acridinone derivates C-1305 and C-1311 are promising antitumor agents with high activity against several experimental cellular and tumor models and which are under evaluation in pre-clinical and early phase clinical trials. Recent evidence from our laboratories has indicated that both compounds were conjugated by several UGT isoforms with the most active being extrahepatic UGT1A10. The present studies were designed to test...
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Targeting of FLT3-ITD kinase contributes to high selectivity of imidazoacridinone C-1311 against FLT3-activated leukemia cells
PublikacjaDrugs targeting receptor tyrosine kinase FLT3 are of particular interest since activating FLT3-internal tandem duplication (ITD) mutations abundantly occur in fatal acute myeloid leukemias (AMLs). Imidazoacridinone C-1311, a DNA-reactive inhibitor of topoisomerase II, has been previously shown to be a potent and selective inhibitor of recombinant FLT3. Here, we expand those findings by studying its effect on leukemia cells with...
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Investigation of an elutable N-propylphosphonic acid chitosan derivative composition with a chitosan matrix prepared from carbonic acid solution
PublikacjaPorous chitosan composites using CO2 dissolution procedure and including water soluble N-propylphosphonic chitosan derivative (p-CHI) were obtained and characterized. In contrast to the control material, composites containing modified chitosan distinguished by a rapid moisture absorption and good adhesion to the skin. The FTIR analysis confirmed the presence of propylphosphonic group in the structure of the polymer. The porosity...
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CYP3A4-dependent cellular response does not relate to CYP3A4-catalysed metabolites of C-1748 and C-1305 acridine antitumor agents in HepG2 cells
PublikacjaHigh CYP3A4 expression sensitizes tumor cells to certain antitumor agents while for others it can lower their therapeutic ef fi cacy. We have elucidated the in fl uence of CYP3A4 overexpression on the cellular response induced by antitumor acridine derivatives, C-1305 and C-1748, in two hepatocellular carcinoma (HepG2) cell lines, Hep3A4 stably transfected with CYP3A4 isoenzyme, and HepC34 expressing empty vector. The compounds...
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The Influence of Antitumor Unsymmetrical Bisacridines on 3D Cancer Spheroids Growth and Viability
PublikacjaThe culture of 3D spheroids is a promising tool in drug development and testing. Recently, we synthesized a new group of compounds, unsymmetrical bisacridines (UAs), which exhibit high cytotoxicity against various human cell lines and antitumor potency against several xenografts. Here, we describe the ability of four UAs—C-2028, C-2041, C-2045, and C-2053—to influence the growth of HCT116 and H460 spheres and the viability of HCT116...
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CYP3A4 overexpression enhances apoptosis induced by anticancer agent imidazoacridinone C-1311, but does not change the metabolism of C-1311 in CHO cells
PublikacjaWe examine whether CYP3A4 overexpression influences the rate and pattern of antitumor imidazoacridinone C-1311 metabolism, in relation to the impact of this overexpression on cell cycle progression and final cellular response of CHO cells following C-1311 treatment. Methods: Three CHO cell lines: CHO-WT, wild type, CHO-HR, overexpressing cytochrome P450 reductase (CPR) and CHO-HR-3A4, coexpressing CPR and CYP3A4 were applied....
wyświetlono 2777 razy