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Wyniki wyszukiwania dla: APOPTOSIS
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Application of Oil-in-Water Nanoemulsion Carrying Size-Defined Gold Nanoparticles Synthesized by Non-thermal Plasma for the Human Breast Cancer Cell Lines Migration and Apoptosis
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Integrating Statistical and Machine‐Learning Approach for Meta‐Analysis of Bisphenol A‐Exposure Datasets Reveals Effects on Mouse Gene Expression within Pathways of Apoptosis and Cell Survival
PublikacjaBisphenols are important environmental pollutants that are extensively studied due to different detrimental effects, while the molecular mechanisms behind these effects are less well understood. Like other environmental pollutants, bisphenols are being tested in various experimental models, creating large expression datasets found in open access storage. The meta‐analysis of such datasets is, however, very complicated for various...
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α-Lipoic Acid Strengthens the Antioxidant Barrier and Reduces Oxidative, Nitrosative, and Glycative Damage, as well as Inhibits Inflammation and Apoptosis in the Hypothalamus but Not in the Cerebral Cortex of Insulin-Resistant Rats
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Ceragenin CSA-13 as free molecules and attached to magnetic nanoparticle surfaces induce caspase-dependent apoptosis in human breast cancer cells via disruption of cell oxidative balance
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Constituents of Propolis: Chrysin, Caffeic Acid, p-Coumaric Acid, and Ferulic Acid Induce PRODH/POX-Dependent Apoptosis in Human Tongue Squamous Cell Carcinoma Cell (CAL-27)
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Chemical variability of Rhododendron tomentosum (Ledum palustre) essential oils and their pro-apoptotic effect on lymphocytes and rheumatoid arthritis synoviocytes
PublikacjaRhododendron tomentosum (Ledum palustre) is an aromatic plant traditionally used for alleviating rheumatic complaints which makes it a potential candidate for a natural drug in rheumatoid arthritis (RA) treatment. However, the effects of plants’ volatiles on apoptosis of synovial fibroblasts and infiltrating leucocytes of RA synovia, have not been reported. Volatile fraction of R. tomentosum is chemically variable and chemotypes...
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Modulation of G2 arrest enhances cell death induced by the antitumor 1-nit-roacridine derivative, Nitracrine
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The Influence of Cold Atmospheric Pressure Plasma-Treated Media on the Cell Viability, Motility, and Induction of Apoptosis in Human Non-Metastatic (MCF7) and Metastatic (MDA-MB-231) Breast Cancer Cell Lines
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Ameliorative Role of Cerium Oxide Nanoparticles Against Fipronil Impact on Brain Function, Oxidative Stress, and Apoptotic Cascades in Albino Rats
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Novel 5-Substituted 2-(Aylmethylthio)-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl)benzenesulfonamides: Synthesis, Molecular Structure, Anticancer Activity, Apoptosis-Inducing Activity and Metabolic Stability
PublikacjaA series of novel 5-substituted 2-(arylmethylthio)-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl) benzenesulfonamide derivatives 27–60 have been synthesized by the reaction of aminoguanidines with an appropriate phenylglyoxal hydrate in glacial acetic acid. A majority of the compounds showed cytotoxic activity toward the human cancer cell lines HCT-116, HeLa and MCF-7, with IC50 values below 100 M. It was found that for the analogues 36–38...
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Pro-apoptotic action of protein-carbohydrate fraction isolated from coelomic fluid of the earthworm Dendrobaena veneta against human colon adenocarcinoma cells
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Isolation of xanthone and benzophenone derivatives from Cyclopia genistoides (L.) Vent. (honeybush) and their pro-apoptotic activity on synoviocytes from patients with rheumatoid arthritis
PublikacjaA fast and efficient method for the isolation of the C-glucosidated xanthones mangiferin and isomangiferin from the South-African plant Cyclopia genistoides was developed for the first time. Two benzophenone derivatives: 3-C-β-glucosides of maclurin and iriflophenone, were isolated from C. genistoides extracts using semi-preparative. The structures of the compounds were determined by 1D and 2D NMR experiments and/or LC-DAD-ESI–MS.
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Novel 2-alkythio-4-chloro-N-[imino(heteroaryl)methyl]benzenesulfonamide Derivatives: Synthesis, Molecular Structure, Anticancer Activity and Metabolic Stability
PublikacjaA series of novel 2-alkythio-4-chloro-N-[imino-(heteroaryl)methyl]benzenesulfonamide derivatives, 8–24, were synthesized in the reaction of the N-(benzenesulfonyl)cyanamide potassium salts 1–7 with the appropriate mercaptoheterocycles. All the synthesized compounds were evaluated for their anticancer activity in HeLa, HCT-116 and MCF-7 cell lines. The most promising compounds, 11–13, molecular hybrids containing benzenesulfonamide...
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Impact of heat shock transcription factor 1 on global gene expression profiles in cells which induce either cytoprotective or pro-apoptotic response following hyperthermia
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The overexpression of CPR and P450 3A4 in pancreatic cancer cells changes the metabolic profile and increases the cytotoxicity and pro-apoptotic activity of acridine antitumor agent, C-1748
PublikacjaDrug resistance is one of the major cause of pancreatic cancer treatment failure. Thus, it is still imperative to develop new active compounds and novel approach to improve drug efficacy. Here we present 9-amino-1-nitroacridine antitumor agent, C-1748, developed in our laboratory, as a candidate for pancreatic cancer treatment. We examined (i) the cellular response of pancreatic cancer cell lines: Panc-1, MiaPaCa-2, BxPC-3 and...
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Panax quinquefolium L. Ginsenosides from Hairy Root Cultures and Their Clones Exert Cytotoxic, Genotoxic and Pro-Apoptotic Activity towards Human Colon Adenocarcinoma Cell Line Caco-2
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Synthesis of 3-(2-Alkylthio-4-chloro-5-methylbenzenesulfonyl)-2-(1-phenyl-3-arylprop-2-enylideneamino)guanidine Derivatives with Pro-Apoptotic Activity against Cancer Cells
PublikacjaThe untypical course of reaction between chalcones and benzenesulfonylaminoguanidines led to the new 3-(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-2-(1-phenyl-3-arylprop-2- enylideneamino)guanidine derivatives 8–33. The new compounds were tested in vitro for their impact on the growth of breast cancer cells MCF-7, cervical cancer cells HeLa and colon cancer cells HCT-116 by MTT assay. The results revealed that the activity of...
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Novel therapeutic compound acridine–retrotuftsin action on biological forms of melanoma and neuroblastoma
PublikacjaPURPOSE: As a continuation of our search for anticancer agents, we have synthesized a new acridine-retrotuftsin analog HClx9-[Arg(NO2)-Pro-Lys-Thr-OCH3]-1-nitroacridine (named ART) and have evaluated its activity against melanoma and neuroblastoma lines. Both tumors develop from cells (melanocytes, neurons) of neuroectodermal origin, and both are tumors with high heterogeneity and unsatisfactory susceptibility to chemotherapies....
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Enhanced Activity of P4503A4 and UGT1A10 Induced by Acridinone Derivatives C-1305 and C-1311 in MCF-7 and HCT116 Cancer Cells: Consequences for the Drugs’ Cytotoxicity, Metabolism and Cellular Response
PublikacjaActivity modulation of drug metabolism enzymes can change the biotransformation of chemotherapeutics and cellular responses induced by them. As a result, drug-drug interactions can be modified. Acridinone derivatives, represented here by C-1305 and C-1311, are potent anticancer drugs. Previous studies in non-cellular systems showed that they are mechanism-based inhibitors of cytochrome P4503A4 and undergo glucuronidation via UDP-glucuronosyltranspherase...
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Study of the anticancer potential of Cd complexes of selenazoyl-hydrazones and their sulfur isosters
PublikacjaThe biological activity of Cd compounds has been investigated scarce since Cd has been recognized as a human carcinogen. However, the toxicity of cadmium is comparable to the toxicity of noble metals such as Pt and Pd. The paradigm of metal toxicity has been challenged suggesting that metal toxicity is not a constant property, yet it depends on many factors like the presence of appropriate ligands. Studies on anticancer activity...
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Screening of predicted synergistic multi-target therapies in glioblastoma identifies new treatment strategies
PublikacjaAbstract Background IDH-wildtype glioblastoma (GBM) is a highly malignant primary brain tumor with a median survival of 15 months after standard of care, which highlights the need for improved therapy. Personalized combination therapy has shown to be successful in many other tumor types and could be beneficial for GBM patients. Methods We performed the largest drug combination screen to date in GBM, using a high-throughput effort...
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Use of Escherichia coli Nissle 1917 producing recombinant colicins for treatment of IBD patients
PublikacjaPatients with Crohn’s Disease and ulcerative colitis infected with Adherent-Invasive Escherichia coli strains constitute the largest group among Inflammatory Bowel Disease subjects, when taking into account all known etiological agents of the disease. A possible link between these pathogenic bacteria and inflammation process has gained the confidence in recently published papers. Observed enteric neuroglial cells apoptosis and...
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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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PARP inhibition potentiates the cytotoxic activity of C-1305, a selective inhibitor of topoisomerase II, in human BRCA1-positive breast cancer cells
PublikacjaTwo cellular proteins encoded by the breast and ovarian cancer type 1 susceptibility (BRCA1 and BRCA2) tumor suppressor genes are essential for DNA integrity and the maintenance of genomic stability.Approximately 5-10% of breast and ovarian cancers result from inherited alterations or mutations in these genes.Remarkably, BRCA1/BRCA2-deficient cells are hypersensitive to selective inhibition of poly(ADPribose) polymerase 1 (PARP-1),...
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New 2-[(4-Amino-6-N-substituted-1,3,5-triazin-2-yl)methylthio]-N-(imidazolidin-2-ylidene)-4-chloro-5-methylbenzenesulfonamide Derivatives, Design, Synthesis and Anticancer Evaluation
PublikacjaIn the search for new compounds with antitumor activity, new potential anticancer agents were designed as molecular hybrids containing the structures of a triazine ring and a sulfonamide fragment. Applying the synthesis in solution, a base of new sulfonamide derivatives 20–162 was obtained by the reaction of the corresponding esters 11–19 with appropriate biguanide hydrochlorides. The structures of the compounds were confirmed...
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9,10-Dioxoanthracenyldithiocarbamates effectively inhibit the proliferation of non-small cell lung cancer by targeting multiple protein tyrosine kinases
PublikacjaAnthraquinones have attracted considerable interest in the realm of cancer treatment owing to their potent anticancer properties. This study evaluates the potential of a series of new anthraquinone derivatives as anticancer agents for non-small-cell lung cancer (NSCLC). The compounds were subjected to a range of tests to assess their cytotoxic and apoptotic properties, ability to inhibit colony formation, pro-DNA damage functions,...
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Genome-wide DNA methylation profiling of the regenerative MRL/MpJ mouse and two normal strains
PublikacjaAims We aimed to identify the pivotal differences in the DNA methylation profiles between the regeneration capable MRL/MpJ mouse and reference mouse strains. Materials and Methods Global DNA methylation profiling was performed in ear pinnae, bone marrow, spleen, liver, heart from uninjured adult females of the MRL/MpJ and C57BL/6J and BALB/c. Results and conclusion A number of differentially methylated regions distinguishing between...
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The cellular response of human hepatoma cells with different expression of CYP3A4 isoenzyme to treatment with triazoloacridinone derivative C-1305
PublikacjaCelem badań było określenie w jaki sposób ekspresja enzymów odpowiedzialnych za metabolizm pochodnej triazoloakrydonu C-1305 wpływa na odpowiedź komórek ludzkiego raka wątroby HepG2 i Hep3A4. W komórkach HepG2 triazoloakrydon C-1305 indukuje proces starzenia, podczas gdy w przypadku linii Hep3A4, komórki ulegają apoptozie oraz nekrozie.
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Chloroacridine derivatives as potential anticancer agents which may act as tricarboxylic acid cycle enzyme inhibitors
PublikacjaThe chloroacridines affect biological forms of melanoma in different ways. Amelanotic (Ab) melanoma (with inhibited melanogenesis and higher malignancy) was particularly sensitive to the action of the chloroacridines. The Ab melanoma cells died through apoptosis and through death without caspase activation. Diminished activity of TAC enzymes was noticed among Ab melanoma cells together with ATP/NAD depletion, especially in the...
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Synthesis, Molecular Structure, Anticancer Activity, and QSAR Study of N-(aryl/heteroaryl)-4-(1H-pyrrol-1-yl)Benzenesulfonamide Derivatives
PublikacjaA series of N-(aryl/heteroaryl)-4-(1H-pyrrol-1-yl)benzenesulfonamides were synthesized from 4-amino-N-(aryl/heteroaryl)benzenesulfonamides and 2,5-dimethoxytetrahydrofuran. All the synthesized compounds were evaluated for their anticancer activity on HeLa, HCT-116, and MCF-7 human tumor cell lines. Compound 28, bearing 8-quinolinyl moiety, exhibited the most potent anticancer activity against the HCT-116, MCF-7, and HeLa cell lines,...
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Utilizing Genome-Wide mRNA Profiling to Identify the Cytotoxic Chemotherapeutic Mechanism of Triazoloacridone C-1305 as Direct Microtubule Stabilization
PublikacjaRational drug design and in vitro pharmacology profiling constitute the gold standard in drug development pipelines. Problems arise, however, because this process is often dicult due to limited information regarding the complete identification of a molecule’s biological activities. The increasing aordability of genome-wide next-generation technologies now provides an excellent opportunity to understand a compound’s diverse eects...
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Novel chalcone-derived pyrazoles as potential therapeutic agents for the treatment of non-small cell lung cancer
PublikacjaLung cancer is considered to account for approximately one-fifth of all malignant tumor-related deaths worldwide and is therefore one of the most lethal malignancies. Pyrazole scaffold possesses a wide range of biological and pharmacological activities, which play important roles in medicinal chemistry. The present study reports the synthesis and in vitro biological characterization of nine pyrazoles derived from chalcones as potential...
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Cytokine IL6, but not IL-1β, TNF-α and NF-κB is increased in paediatric cancer patients
PublikacjaCytokines are responsible for maintaining homeostasis as cell growth, differentiation, migration and apoptosis mediators. They play a pivotal role in immune responses to inflammatory reactions. In oncological diseases, the cross-talk between cells of the immunological system and cells of the tumour microenvironment is led by cytokines. Also, the overproduction of cytokines may change the tumour microenvironment and stimulate tumour...
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Teloxantron inhibits the processivity of telomerase with preferential DNA damage on telomeres
PublikacjaTelomerase reactivation is one of the hallmarks of cancer, which plays an important role in cellular immortalization and the development and progression of the tumor. Chemical telomerase inhibitors have been shown to trigger replicative senescence and apoptotic cell death both in vitro and in vivo. Due to its upregulation in various cancers, telomerase is considered a potential target in cancer therapy. In this study, we identified...
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Telomere uncapping by common oxidative guanine lesions: Insights from atomistic models
PublikacjaOxidative damage to DNA is widely known to contribute to aging and disease. This relationship has been extensively studied for telomeres – structures that cap chromosome ends – due to their role in cell proliferation and senescence, and exceptional susceptibility to oxidation. Indeed, the repetitive telomeric DNA sequence contains the 5′-GGG-3′ motif that has the lowest ionization potential of all trinucleotides. Accordingly, experiments...
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Synthesis and Biological Evaluation of Acridine/Acridone Analogs as Potential Anticancer Agents
PublikacjaAcridine and acridone analogues were prepared by Ullmann condensation and then cyclization reaction. As a result of nucleophilic substitution reaction 1-nitro-9-phenoxyacridine or 1-chloro-4-nitro-9(10H)-acridone with the corresponding peptides, the planned acridine derivatives (10a-c, 12, 17-a-d, 19) have been obtained. The cytotoxic activity of the newly obtained analogs were evaluated against melanotic (Ma) and amelanotic (Ab)...
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The Unfolded Protein Response: A Double-Edged Sword for Brain Health
PublikacjaEfficient brain function requires as much as 20% of the total oxygen intake to support normal neuronal cell function. This level of oxygen usage, however, leads to the generation of free radicals, and thus can lead to oxidative stress and potentially to age-related cognitive decay and even neurodegenerative diseases. The regulation of this system requires a complex monitoring network to maintain proper oxygen homeostasis. Furthermore,...
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The response of human colon cancer cells to C-1748 (4-methyl-1-nitroacridine derivative) treatment
PublikacjaPrzeprowadzone badania miały na celu określenie wpływu pochodnej 4-metylo-1-nitroakrydyny C-1748 na komórki ludzkiego raka okrężnicy HCT8 oraz HT29. Komórki obu linii, traktowane badanym związkiem, ulegały przede wszystkim apoptozie, przy czym liczba komórek apoptotycznych była znacznie większa w przypadku linii HCT8. Ponadto, proliferacja części komórek HCT8, została zahamowana w wyniku uruchomienia procesu starzenia, czego nie...
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Anticancer Imidazoacridinone C-1311 is Effective in Androgen-Dependent and Androgen-Independent Prostate Cancer Cells
PublikacjaAndrogen receptor (AR) plays a crutial role in prostate cancer (PCa) development and metastasis. Here, we reported potent anti-PCa activity of a small molecule imidazoacridinone C-1311. In AR-positive PCa cells, C-1311 was found to inhibit the transcriptional activity of AR uncovering a novel mechanism that may be relevant for its anticancer effect. Mechanistically, C-1311 decreased AR binding to prostate-specific antigen (PSA)...
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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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Cellular Effects of Selected Unsymmetrical Bisacridines on the Multicellular Tumor Spheroids of HCT116 Colon and A549 Lung Cancer Cells in Comparison to Monolayer Cultures
PublikacjaMulticellular tumor spheroids are a good tool for testing new anticancer drugs, including those that may target cancer stem cells (CSCs), which are responsible for cancer progression, metastasis, and recurrence. Therefore, we applied this model in our studies of highly active antitumor unsymmetrical bisacridines (UAs). We investigated the cellular response induced by UAs in 2D and 3D cultures of HCT116 colon and A549 lung cancer...
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Changes in Epigenetic Patterns Related to DNA Replication in Vicia faba Root Meristem Cells under Cadmium-Induced Stress Conditions
PublikacjaExperiments on Vicia faba root meristem cells exposed to 150 µM cadmium chloride (CdCl2) were undertaken to analyse epigenetic changes, mainly with respect to DNA replication stress. Histone modifications examined by means of immunofluorescence labeling included: (1) acetylation of histone H3 on lysine 56 (H3K56Ac), involved in transcription, S phase, and response to DNA damage during DNA biosynthesis; (2) dimethylation of histone...
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The cellular response of human colon carcinoma HCT116 cells to 4-methyl-1-nitroacridine derivative C-1748 treatment depending on p53 status
PublikacjaWykazano, że pochodna C-1748 indukuje apoptozę w komórkach linii ludzkich raków jelita grubego HCT116 p53+/+ i p53-/- w sposób zależny od czasu inkubacji i stężenia związku. Wskazują na to: pojawienie się frakcji komórek sub-G1, charakterystyczne zmiany w morfologii jąder komórkowych, zmiany w strukturze błony plazmatycznej. Ponadto, pod wpływem badanego związku komórki HCT116 p53+/+ wykazują większą podatność do ulegania apoptozie...
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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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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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Modulation of CYP19 expression by cabbage juices and their active components: indole-3-carbinol and 3,30-diindolylmethene in human breast epithelial cell lines
PublikacjaThe aim of this study was to evaluate the effect of white cabbage and sauerkraut juices of different origin and indole-3-carbinol (I3C) and diindolylmethane (DIM) on expression of CYP19 gene encoding aromatase, the key enzyme of estrogen synthesis.Remarkable differences in the effect on CYP19 transcript and protein level were found between the cab- bage juices (in 2.5-25 mL/L concentrations) and indoles (in 2.5-50 lM doses) in...
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The effect of sunscreen 4‐methylbenzylidene camphor in different and reproductive models, its bioaccumulation and molecular effects on ligand‐receptor interaction, and protein expression
Publikacja4-Methylbenzylidene camphor (4-MBC) is a photo-absorbing UV filter prevalently used in cosmetics, which can be absorbed into circulation and cause systemic effects. 4-MBC is continued to be released in the environment despite the growing knowledge about its bioaccumulation and endocrine disrupting effects. Previous reviews have mentioned UV-filter together but this review considers 4-MBC alone, due to its prevalence and concerning...
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In vitro biological evaluation of a novel folic acid-targeted receptor quantum dot−β−cyclodextrin carrier for C-2028 unsymmetrical bisacridine in the treatment of human lung and prostate cancers
PublikacjaTraditional small-molecule chemotherapeutics usually do not distinguish tumors from healthy tissues. However, nanotechnology creates nanocarriers that selectively deliver drugs to their site of action. This work is the next step in the development of the quantum dot−β−cyclodextrin−folic acid (QD−β−CD−FA) platform for targeted and selected delivery of C−2028 unsymmetrical bisacridine in cancer therapy.Herein, we report an initial...
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Comparison of 2D and 3D culture models in the studies of the biological response induced by unsymmetrical bisacridines in cancer cells
PublikacjaMulticellular tumor spheroids are a good tool for testing new anticancer drugs, including those that may target cancer stem cells (CSCs), responsible for cancer progression, metastasis, and recurrence. Therefore, following the initial evaluation of the impact of antitumor unsymmetrical bisacridines (UAs) on lung and colon cancer cells using traditional monolayer cultures, I extended my investigations and applied the spherical model....
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Post-Effort Changes in Autophagy- and Inflammation-Related Gene Expression in White Blood Cells of Healthy Young Men
PublikacjaAcute, strenuous physical exertion requiring high levels of energy production induces the production of reactive oxygen species and metabolic disturbances that can damage the mitochondria. Thus, selective autophagic elimination of defective mitochondria may improve resistance to oxidative stress and potentially to inflammation. The main goal of this study was to evaluate the impacts of intense effort on changes in the expression...