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Wyniki wyszukiwania dla: CANCER CELLS, CELLULAR RESPONSE, C-1748
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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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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 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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Antitumor 1-nitroacridine derivative C-1748 induces significant apoptosis in pancreatic cancer cells.
PublikacjaPancreatic cancer is the fifth leading cause of cancer death and has the lowest survival rate of any solid cancer in the industrial countries. The poor prognosis of pancreatic cancer results from its tendency for late presentation, aggressive invasion, early metastasis, and resistance to chemotherapy. Gemcitabine still remains the best chemotherapeutic agent available for the treatment of advanced pancreatic cancer. However, gemcitabine...
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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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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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Oxidative stress induced by 4-methyl-1-nitroacridine derivative C-1748 (Capridine B) in human colon cancer cells
PublikacjaZbadano wpływ pochodnej C-1748 (Capridine B) na indukcję stresu oksydacyjnego w komórkach ludzkich raków jelita grubego HCT-8 i HT29. W tym celu wykorzystano technikę cytometrii przepływowej z zastosowaniem barwników fluorescencyjnych H2DCFDA i DHR 123. W komórkach traktowanych pochodną C-1748 dochodziło do generowania reaktywnych form tlenu. Ponadto, pochodna C-1748 nie indukowała znaczącego spadku zawartości zredukowanej formy...
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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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Induction of G2/M phase arrest and apoptosis of human pancreatic cancer BxPC-3 cells by potenet antitumor 1-nitroacridine derivative C-1748
PublikacjaPancreatic ductal adenocarcinoma (PDA) is among the most lethal human cancers, in part because it is insensitive to many chemotherapeutic drugs. Gemcitabine still remains the best chemotherapeutic agent available for the treatment of advanced pancreatic cancer. However, gemcitabine treatment results in only a marginal survival advantage. Thus, there is a strong need for the continuous development of novel therapeutic agents...
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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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Different expression level of CYP3A4 isoenzyme modulate cellular response of CHO cells following treatment with the CYP3A4 inhibitor, C-1311 compound
PublikacjaEfektywność terapii przeciwnowotworowej może być zmieniana przez różne czynniki. Jednym z ograniczeń jest odmienny u każdego pacjenta poziom enzymów metabolizujących odpowiedzialnych za aktywację i detoksykację leków, co może zmieniać jego odpowiedź na zastosowaną terapię. Co więcej, enzymy metabolizujące często są celem molekularnym wielu ksenobiotyków, co dodatkowo może zmieniać skuteczność terapii. Zatem zrozumienie oddziaływań...
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The increased level of cytochrome P450 isoenzyme CYP3A4 affects the cellular response in CHO cells upon antitumor imidazoacridinone C-1311 treatment
PublikacjaPochodna C-1311 to potencjalny związek przeciwnowotworowy, który dotarł do II fazy badań klinicznych. Związek ten ulega metabolicznej transformacji pod wpływem szczurzych i ludzkich białek mikrosomalnych. Wykazano, że białka cytochromu P450 odpowiadają za przemiany metaboliczne C-1311 jedynie w niewielkim stopniu. Z drugiej strony wykazano, że pochodna C-1311 jest inhibitorem białek cytochromu P450, zwłaszcza izoenzymu CYP1A2...
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Analysis of cellular response induced by imidazoacridinone derivative C-1311 in Chinese hamster ovary carcinoma cells CHO with vorious expression level of cytochrome P450 reductase
PublikacjaRodzaj odpowiedzi komórkowej indukowanej przez pochodną C-1311 badany był w komórkach CHO o różnym poziomie reduktazy cytochromu P450. Wszystkie eksperymenty zostały przeprowadzone przy zastosowaniu stężenia związku odpowiadającego dawce EC80. Poziom ekspresji reduktazy cytochromu P450 nie miał istotnego wpływu na rodzaj odpowiedzi komórkowej indukowanej przez pochodną C-1311. Głównym efektem biologicznym wywieranym przez badany...
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Antitumor imidazoacridinone derivative C-1311 induces cell cycle arrest and cellular senescence-like phenotypic changes in human non-small lung A549 cancer cells
PublikacjaPrzeprowadzone badania miały na celu zbadanie rodzaju odpowiedzi komórkowej indukowanej przez pochodną C1311 w komórkach ludzkiego, niedrobnokomórkowego raka płuc A549, wyselekcjonowanych do badań ze względu na wysoką wrażliwość na działanie pochodnej C-1311. Wszystkie eksperymenty przeprowadzone zostały przy stężeniu hamującym proliferację komórek nowotworowych w 80%. Badania z wykorzystaniem techniki cytometrii przepływowej oraz...
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The time-dependent cellular uptake of C−2028, CD−C−2028, QDgreen−C−2028, and QDgreen−CD−FA−C−2028 conjugates at IC80 value to cancer LNCaP cells
Dane BadawczeThe time-dependent (1, 24, 48, and 72 h) cellular uptake of C−2028, CD−C−2028, QDgreen−C−2028, and QDgreen−CD−FA−C−2028 conjugates at IC80 value to cancer LNCaP cells performed by Confocal Laser Scanning Microscopy (63× magnification; ZEISS LSM T-PMT, Magdeburg, Germany). Based on the fluorescence properties of these compounds, green and orange fluorescence...
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The time-dependent cellular uptake of C−2028, CD−C−2028, QDgreen−C−2028, and QDgreen−CD−FA−C−2028 conjugates at IC80 value to cancer H460 cells
Dane BadawczeThe time-dependent (1, 24, 48, and 72 h) cellular uptake of C−2028, CD−C−2028, QDgreen−C−2028, and QDgreen−CD−FA−C−2028 conjugates at IC80 value to cancer H460 cells performed by Confocal Laser Scanning Microscopy (63× magnification; ZEISS LSM T-PMT, Magdeburg, Germany). Based on the fluorescence properties of these compounds, green and orange fluorescence...
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The time-dependent cellular uptake of C−2028, CD−C−2028, QDgreen−C−2028, and QDgreen−CD−FA−C−2028 conjugates at IC80 value to cancer Du-145 cells
Dane BadawczeThe time-dependent (1, 24, 48, and 72 h) cellular uptake of C−2028, CD−C−2028, QDgreen−C−2028, and QDgreen−CD−FA−C−2028 conjugates at IC80 value to cancer Du-145 cells performed by Confocal Laser Scanning Microscopy (63× magnification; ZEISS LSM T-PMT, Magdeburg, Germany). Based on the fluorescence properties of these compounds, green and orange fluorescence...
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c-Myc Protein Level Affected by Unsymmetrical Bisacridines Influences Apoptosis and Senescence Induced in HCT116 Colorectal and H460 Lung Cancer Cells
PublikacjaUnsymmetrical bisacridines (UAs) are highly active antitumor compounds. They contain in their structure the drugs previously synthesized in our Department: C-1311 and C-1748. UAs exhibit different properties than their monomer components. They do not intercalate to dsDNA but stabilize the G-quadruplex structures, particularly those of the MYC and KRAS genes. Since MYC and KRAS are often mutated and constitutively expressed in cancer...
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Metabolism of antitumour agent 1-nitroacridine derivative, C-1748 in pancreatic cancer cell lines
PublikacjaPancreatic cancer has the highest mortality rate of all major cancers because of limited treatment options. Surgical removal of the tumour is possible only in its early stage, nevertheless the asymptomatic development very often makes unable an accurate diagnose. In the case of metastatic pancreatic cancer only chemotherapy, mainly with gemcitabine, can be offered to patients. However, common resistance towards gemcitabine imposes...
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Antitumor DNA-Damaging C-1748 is a New Inhibitor of Autophagy that Triggers Apoptosis in Human Pancreatic Cancer Cell Lines
PublikacjaDespite the enormous progress that has been made over the past decades in diagnosis, treatment and prevention of many types of tumors, survival rates in pancreatic cancer still remain poor. Pancreatic cancer is one of the most malignant and chemoresistant tumors and the profound mechanism supporting these phenomena is the constitutively activated prosurvival autophagy. The antitumor 1-nitroacridine derivative C-1748 belongs to...
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Diminshed toxicity of C-1748, 4-methyl-9-hydroxyethylamino-1-nitroacridine, compared with its demethyl analog, C-857, corresponds to its resistance to metabolism in HepG2 cells
PublikacjaThe narrow "therapeutic window" of anti-tumour therapy may be the result of drug metabolism leading to the activation or detoxification of antitumour agents. The aim of this work is to examine (i) whether the diminished toxicity of a potent antitumour drug, C-1748, 9-(2'-hydroxyethylamino)-4-methyl-1-nitroacridine, compared with its 4-demethyl analogue, C-857, results from the differences between the metabolic pathways for the...
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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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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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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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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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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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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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c-Myc inhibition and p21 modulation contribute to unsymmetrical bisacridines-induced apoptosis and senescence in pancreatic cancer cells
PublikacjaBackground Pancreatic cancer (PC) is one of the most aggressive cancers and is the seventh leading cause of cancer-related death worldwide. PC is characterized by rapid progression and resistance to conventional treatments. Mutations in KRAS, CDKN2A, TP53, SMAD4/DPC4, and MYC are major genetic alterations associated with poor treatment outcomes in patients with PC. Therefore, optimizing PC therapy is a tremendous challenge. Unsymmetrical...
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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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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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Drug-drug interaction potential of antitumor acridine agent C-1748: The substrate of UDP-glucuronosyltransferases 2B7, 2B17 and the inhibitor of 1A9 and 2B7
PublikacjaBackground The compound 9-(2′-hydroxyethylamino)-4-methyl-1-nitroacridine (C-1748), the promising antitumor agent developed in our laboratory was determined to undergo phase I metabolic pathways. The present studies aimed to know its biotransformation with phase II enzymes – UDP-glucuronosyltransferases (UGTs) and its potential to be engaged in drug-drug interactions arising from the modulation of UGT activity. Methods UGT-mediated...
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Quantum dots conjugates with unsymmetrical bisacridines enhance cytotoxicity of these antitumor compounds in lung cancer cells and have protecting effects on normal cells
PublikacjaBackground: In recent years, with the rapid development of nanotechnology and its extensive applications in the medicine, nanocarriers for anticancer drug delivery have gained a great importance. Spherical semiconductor nanocrystals, frequently called quantum dots (QDs) are very attractive nanomaterials for bioimaging applications and they possess properties as potential candidates for drug carrier. Unsymmetrical bisacridines (UAs),...
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Human UDP-Glucuronosyltransferases: Effects of altered expression in breast and pancreatic cancer cell lines.
PublikacjaIncreased aerobic glycolysis and de novo lipid biosynthesis are common characteristics of invasive cancers. UDP-glucuronosyltransferases (UGTs) are phase II drug metabolizing enzymes that in normal cells possess the ability to glucuronidate these lipids and speed their excretion; however, de-regulation of these enzymes in cancer cells can lead to an accumulation of bioactive lipids, which further fuels cancer progression. We hypothesize...
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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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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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Modified Peptide Molecules As Potential Modulators of Shelterin Protein Functions; TRF1
PublikacjaIn this work, we present studies on relatively new and still not well-explored potential anticancer targets which are shelterin proteins, in particular the TRF1 protein can be blocked by in silico designed "peptidomimetic" molecules. TRF1 interacts directly with the TIN2 protein, and this protein-protein interaction is crucial for the proper functioning of telomere, which could be blocked by our novel modified peptide molecules....
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Modulation of UDP-glucuronidation by acridinone antitumor agents C-1305 and C-1311 in HepG2 and HT29 cell lines, despite slight impact in noncellular systems.
PublikacjaBackground Among the studied antitumor acridinone derivatives developed in our laboratory, 5-dimethylaminopropylamino-8-hydroxytriazoloacridinone (C-1305) and 5-diethylaminoethylamino-8-hydroxyimidazoacridinone (C-1311) exhibited cytotoxic and antitumor properties against several cancer types and were selected to be evaluated in preclinical and early-phase clinical trials. In the present work, we investigated the impact of C-1305...
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From tryptophan to novel mitochondria-disruptive agent, synthesis and biological evaluation of 1,2,3,6-tetrasubstituted carbazoles
PublikacjaMitochondrial targeting plays an important role in anticancer therapy. The Mn(III)-promoted cyclization of 5- (1H-indol-3-yl)-3-oxopentanoic acid allow to obtain novel substituted carbazole derivatives that can act as mitochondria-disruptive agents. The starting materials used for the synthesis of these new aminocarbazoles are oxopentanoate derivatives of tryptophan. The scope and limitation of this method of synthesis are determined...
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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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In vitro enzyme kinetics and NMR-based product elucidation for glutathione S-conjugation of the anticancer unsymmetrical bisacridine C-2028 in liver microsomes and cytosol: major role of glutathione S-transferase M1-1 isoenzyme
PublikacjaThis work is the next step in studying the interplay between C-2028 (anticancer-active unsymmetrical bisacridine developed in our group) and the glutathione S-transferase/glutathione (GST/GSH) system. Here, we analyzed the concentration- and pH-dependent GSH conjugation of C-2028 in rat liver microsomes and cytosol. We also applied three recombinant human GST isoenzymes, which altered expression was found in various tumors. The...
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CHEMOTHERAPY-MEDIATED COMPLICATIONS OF WOUND HEALING. AN UNDERSTUDIED SIDE EFFECT
PublikacjaSignificance: Chemotherapy is a primary method to treat cancer, but while cytotoxic drugs are designed to target rapidly dividing cancer cells, they can also affect other cell types, including dermal cells and macrophages involved in wound healing, which often leads to the development of chronic wounds. The situation becomes even more severe when chemotherapy is combined with surgical tumor excision. Recent advances: Despite its...
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Acid–Base Equilibrium and Self-Association in Relation to High Antitumor Activity of Selected Unsymmetrical Bisacridines Established by Extensive Chemometric Analysis
PublikacjaUnsymmetrical bisacridines (UAs) represent a novel class of anticancer agents previously synthesized by our group. Our recent studies have demonstrated their high antitumor potential against multiple cancer cell lines and human tumor xenografts in nude mice. At the cellular level, these compounds affected 3D cancer spheroid growth and their cellular uptake was selectively modulated by quantum dots. UAs were shown to undergo metabolic...
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Therapeutic intervention by the simultaneous inhibition of DNA repair and type I or type II DNA topoisomerases: one strategy, many outcomes
PublikacjaMany anticancer drugs reduce the integrity of DNA, forming strand breaks. This can cause mutations and cancer or cell death if the lesions are not repaired. Interestingly, DNA repair-deficient cancer cells (e.g., those with BRCA1/2 mutations) have been shown to exhibit increased sensitivity to chemotherapy. Based on this observation, a new therapeutic approach termed 'synthetic lethality' has been developed, in which radiation...
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Design, synthesis, and biological evaluation of tetrahydroquinolinones and tetrahydroquinolines with anticancer activity
PublikacjaColorectal cancer (CRC) is the most commonly diagnosed cancer in Europe and the United States and the second leading cause of cancer related mortality. A therapeutic strategy used for the treatment of CRC involves targeting the intracellular levels of reactive oxygen species (ROS). In this study, we synthesized a series of novel tetrahydroquinolinones and assessed their ability to inhibit CRC growth and proliferation by evoking...
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Novel fused pyran derivatives induce apoptosis and target cell cycle progression in anticancer efficacy against multiple cell lines.
PublikacjaNitrogen-based heterocycles such as pyrazole, imidazole, 1,2,4-triazole, benzimidazole, and benzotriazole substituted fused pyran derivatives (6a–e, 8a–e, 10a–e, 12a–e,&14a–e) have been synthesized and tested for their in vitro anticancer efficacies against MCF7, A549, and HCT116 cancer cell lines. Among the compounds, 6e, 14b, and 8c were identified as the most potent against MCF7, A549, and HCT116, with IC50 values of 12.46 2.72...
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Potent antitumor 4-methyl-1-nitroacridine C-1748 induces apoptosis only in part of colon cells
PublikacjaZbadaliśmy zdolność pochodnej 4-metylo-1-nitroakrydyny C-1748 do indukcji apoptozy w ludzkich komórkach nowotworów jelita grubego HCT-8 i HT29 w stężeniach biologicznie istotnych. Zjawisko apoptozy określiliśmy na podstawie zmian morfologicznych jak i biochemicznych tj. fragmentacji DNA, aktywacji kaspazy-3, spadku potencjału mitochondrialnego, eksternalizacji fosfatydyloseryny i pojawiania się frakcji sub-G1. Wykazaliśmy, że pochodna...
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Potent antitumor 4-methyl-1-nitroacridine C-1748 induces apoptosis only in part of colon cells
PublikacjaCelem przedstawionej pracy było zbadanie zdolności pochodnej 1-nitroakrydyny C-1748 do indukcji apoptozy komórek raka jelita grubego HCT8 i HT29 pochodzenia ludzkiego. Śmierć komórek była badana przez określony czas inkubacji komórek ze związkiem w stężeniach odpowiadających wartościom EC90 lub ich wielokrotnościom przez czas od 3 do 72 godzin. Uzyskane wyniki wskazują, że C-1748 indukuje apoptozę zależną od czasu tylko w części...
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Emerging anticancer activity of candidal glucoseamine-6-phosphate synthase inhibitors upon nanoparticle-mediated delivery
PublikacjaNumerous glutamine analogues have been reported as irreversible inhibitors of the glucosamine-6-phosphate (GlcN-6-P) synthase in pathogenic Candida albicans in the last 3.5 decades. Among the reported inhibitors, the most effective N3-(4-methoxyfumaroyl)-L-2,3- diaminopropanoic acid (FMDP) has been extensively studied in order to develop its more active analogues. Several peptide−FMDP conjugates were tested to deliver FMDP to its...
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Transcriptomic Effects of Estrogen Starvation and Induction in the MCF7 Cells. The Meta-analysis of Microarray Results
PublikacjaEstrogen is one of the most important signaling molecules which targets a number of genes. Estrogen levels regulate cell proliferation and a plethora of metabolic processes, which may interfere with a range of medical conditions and drug metabolism. The MCF7 breast cancer cell line, expressing the estrogen receptor α, is a well-studied model of cellular answer to estrogen. The aim of this study was to characterize transcriptomic...
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Genotoxic effects of antitumor 1-nitroacridines C-857 and its novel analoque 4-methyl-1-nitroacridine C-1748
Publikacja4-podstawione 1-nitroakrydyny reprezentują nową grupę pochodnych akrydyny zsyntetyzowanych na Politechnice Gdańskiej. W przeprowadzonych badaniach nad pochodnymi C-1748 i C-857 zastosowano dwie metody badawcze: test kometowy oraz zmodyfikowany test mikrojąderkowy (CBMN assay). W teście kometowym wykazano wzrost uszkodzeń DNA w zależności od czasu i stężenia badanych pochodnych 1-nitroakrydyny. Badania aberracji chromosomalnych...