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Clinicopathological analysis of breast ductal carcinoma in situ with ALDH1-positive cancer stem cells.

OBJECTIVE: The aim of this study was to elucidate the clinicopathological characteristics of breast ductal carcinomas in situ (DCIS) with aldehyde dehydrogenase 1 (ALDH1)-positive cancer stem cells (CSCs). METHODS: DCIS (n = 194) were subjected to immunohistochemical staining and results were examined for associations with various clinicopathological parameters. The ALDEFLUOR assay for breast cancer cell lines was also performed to determine the proportion of CSCs according to intrinsic subtype. RESULTS: DCIS with ALDH1-positive CSCs were significantly (p < 0.05) more likely to be estrogen r

Endolysosomal remodeling and acidity dictates ferroptosis sensitivity to iron oxide nanoparticles.

Iron oxide nanoparticles (IONPs) exhibit remarkable anti-tumoral activity, largely mediated by the generation of reactive oxygen species (RO … NPs generate ROS in both cell models, however, their subcellular localization markedly differed. In MDA-MB-231 cells, highly acidic lysosomes retained redox-active iron (Fe2+), leading to localized ROS accumulation, lysosomal enlargement and pronounced lipid peroxidation, ultimately inducing ferroptosis, which was reverted by the anti-ferroptosis drug Ferrostatin- …

The Beta2-adrenergic agonist salbutamol synergizes with paclitaxel on cell proliferation and tumor growth in triple negative breast cancer models.

PURPOSE: Globally breast cancer accounts for 24.5% in incidence and 15.5% in cancer deaths in women. The triple-negative subtype lacks any s … noculated to nude mice and their growth assessed. RESULTS: The β2-agonist salbutamol synergizes in MDA-MB-231 cells in vitro with paclitaxel and doxorubicin on cell proliferation through ADRB2 receptors, while the β-blocker propranolol does not. The expression of this receptor was assessed in patient databases and other cell lines. Triple negative samples had the …

A transposon screen identifies enhancement of NF-κB pathway as a mechanism of resistance to eribulin.

BACKGROUND: Eribulin mesylate (eribulin) is an efficient microtubule inhibitor that is used for metastatic breast cancer. However, breast ca … ntly lower cell viability and higher drug cytotoxicity than single agent treatment with eribulin in MDA-MB-231 cells. However, QNZ increased NF-κB activity in MCF7 cells by up-regulating TAB2, which reduced the sensitivity to eribulin. Furthermore, combination of Bay-117082 with eribulin induced greater regression of MDA-MB-231 tumors compared to eribulin monother …

NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells.

Hyperglycemia, obesity and metabolic syndrome are negative prognostic factors in breast cancer patients. Immune checkpoint inhibitors (ICIs) … ia exacerbates ipilimumab-induced cardiotoxicity and decreases its anticancer efficacy in MCF-7 and MDA-MB-231 cells. This study sets the stage for further tests on other breast cancer cell lines and primary cardiomyocytes and for preclinical trials in mice aimed to decrease glucose through nutritional interventions or administration of gliflozines during treatmen …

The Effect of a Ferrocene Containing Camphor Sulfonamide DK-164 on Breast Cancer Cell Lines.

BACKGROUND: Drug resistance is a major cause of cancer treatment failure. Most cancer therapies involve multiple agents, to overcome it. Compounds that exhibit strong anti-tumor effect without damaging normal cells are more and more in the focus of research. Chemotherapeutic drugs, combining different moieties and functional groups in one molecule, can modulate different regulatory pathways in the cell and thus reach the higher efficacy than the agents, which affect only one cellular process. METHODS: We tested the effect of recently synthesized ferrocene-containing camphor sulfonamide DK-164

Effect of hydrophobic extension of aryl enaminones and pyrazole-linked compounds combined with sulphonamide, sulfaguanidine, or carboxylic acid functionalities on carbonic anhydrase inhibitory potency and selectivity.

Design and synthesis of three novel series of aryl enaminones (3a-f and 5a-c) and pyrazole (4a-c) linked compounds with sulphonamides, sulfaguanidine, or carboxylic acid functionalities were reported as carbonic anhydrase inhibitors (CAIs) using the "tail approach" strategy in their design to achieve the most variable amino acids in the middle/outer rims of the hCAs active site. The synthesised compounds were assessed in vitro for their inhibitory activity against the following human (h) isoforms, hCA I, II, IX, and XII using stopped-flow CO2 hydrase assay. Enaminone sulphonamide derivatives (

Ruthenium(II) Diphosphine Complexes with Mercapto Ligands That Inhibit Topoisomerase IB and Suppress Tumor Growth In Vivo.

Ruthenium(II) complexes (Ru1-Ru5), with the general formula [Ru(N-S)(dppe)2]PF6, bearing two 1,2-bis(diphenylphosphino)ethane (dppe) ligands and a series of mercapto ligands (N-S), have been developed. The combination of these ligands in the complexes endowed hydrophobic species with high cytotoxic activity against five cancer cell lines. For the A549 (lung) and MDA-MB-231 (breast) cancer cell lines, the IC50 values of the complexes were 288- to 14-fold lower when compared to cisplatin. Furthermore, the complexes were selective for the A549 and MDA-MB-231 cancer cell lines compared to the MRC-

Synthesis of novel feruloyl dipeptides with proapoptotic potential against different cancer cell lines.

In this study, a series of novel N-feruloyl dipeptides (10-17) have been synthesized through the coupling of N-feruloyl amino acids (6-9) with glycine/alanine methyl ester hydrochloride. Structures of the peptides were assigned using 1D and 2D NMR and HRESIMS. According to initial in vitro cytotoxic screening against the cervix carcinoma cell line KB-3-1, aromatic dipeptides (12, 13, 16, 17) were the most potent ones among all tested feruloyl dipeptides. Accordingly, these peptides were further intensively investigated as potential anticancer agents against a panel of ten cancer cell lines fro

Effect of Ageratum fastigiatum on Viability, Migration and Proliferation of Breast Cancer Cells in 2D and 3D Culture Models.

Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options, underscoring the need for novel antitumor agents and more physiologically relevant in vitro models. Although species of the Ageratum genus exhibit biological activity, the antitumor potential of Ageratum fastigiatum and its evaluation in three-dimensional (3D) microenvironment have not been previously investigated. This study evaluated the cytotoxic, antiproliferative, and antimigratory effects of the ethanolic extract of Ageratum. fastigiatum on TNBC cells MDA-MB-231 using conventional two-dimensio

Discovery of novel imidazo[1,2-b]pyridazine derivatives as potent covalent inhibitors of CDK12/13.

Triple-negative breast cancer (TNBC) is widely recognized as the most aggressive subtype of breast cancer, and treatment options for patients with TNBC remain highly limited. Recently, cyclin-dependent kinases 12/13 (CDK12/13) have been identified as promising therapeutic targets for TNBC. In our study, we report the design and synthesis of novel imidazo[1,2-b]pyrazine-based covalent inhibitors of CDK12/13, which exhibit potent inhibitory activity against TNBC cells. Among these compounds, compound 24 emerged as the most potent inhibitor, with CDK12 IC50 of 15.5 nM and CDK13 IC50 of 12.2 nM. C

Physical Changes of Biomacromolecules upon Covalent Surface Immobilization.

Immobilization of large biomacromolecules is often required for analytical quantification and physicochemical characterization. However, immobilization can alter the structure and size of the particles being studied. Here, two exosomes (derived from HEK-293 and MDA-MB-231 cells) and three viral particles (Suid herpesvirus 1 (SuHV), xenotropic murine leukemia virus (XmuLV), and porcine parvovirus (PPV)) were immobilized to different covalent chemistries to understand how surface chemistry influences particle deformation during immobilization. The surface chemistries explored were: (i) NHS (N-hy…

Novel Cu(II)-complex loaded Eudragit® nanoparticles: design, synthesis, characterization, and enhanced antitumor activity against triple-negative breast cancer.

Breast cancer (BC) is the most frequently diagnosed malignancy in women and triple-negative breast cancer (TNBC) is its most aggressive subtype of BC, often associated with poor prognosis due to the limited current therapies. Effective delivery systems for metal-based drugs could improve antitumor efficacy and selectivity. In this study, the copper-complex [Cu(N-N-Fur)(NO3)(H2O)] (CuL1), which has demonstrated anticancer activity, was encapsulated into Eudragit®-based nanoparticles to enhance its effects against TNBC cell lines (MDA-MB-231, 4T1, and Hs 578T). Two nanosystems were prepared by n

Приобретение онколитических аденовирусов с последующим лечением от ПД-1 и паклитакселя ведет к повышению эффективности борьбы с раком в модели 3D TNBC.

Трижды отрицательный рак груди (TNBC) считается одним из наиболее неизлечимых магнатов в силу его клинических характеристик, включая высокую инвазивность, высокий метастатический потенциал, подверженность рецидиву и плохое прогнозирование. Поэтому она по-прежнему является одной из важнейших неудовлетворенных медицинских потребностей. С другой стороны, низкая эффективность доставки продолжает снижать эффективность антираковых терапевтических средств, разработанных для борьбы с твердыми опухолями, с использованием различных стратегий, таких, как генетически разработанные онколитические векторы,

Совпадение в аннотации оригинала
Triple-negative breast cancer (TNBC) is considered one of the most incurable malignancies due to its clinical characteristics, including hig … including immunological aspects, we established a three-dimensional (3D) co-culture model based on MDA-MB-231 cells with peripheral blood mononuclear cells (PBMCs) to create an integrated system that more closely mimics the complexity of the tumour microenvironment and interacts with the immune system. Treatment with OV as a priming agent, followed by pembrolizum …

Examining the Role of Asef and Epidermal Growth Factor on Cell Migration and Proliferation in Triple Negative Breast Cancer Epithelial Cells.

Cell proliferation and migration are cellular processes essential to normal cell function; errors in these cellular processes impact the ability of a cell to maintain cellular homeostasis. The current study examines the role of Asef, a GEF for Rac1, in cell proliferation and migration in the presence or absence of EGF in a triple negative breast cancer epithelial cell line. Overexpression of Asef reduced stress fiber formation and increased cell migration and proliferation in MDA-MB-231 epithelial cells. These data indicate a role for Asef in the EGFR/Rac1 signaling cascade involved in regulat

Design, synthesis and anti-breast cancer activity evaluation of 6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine-based PARP1/ATR dual inhibitors.

PARP1 inhibitors are FDA-approved for BRCA1/2-mutated breast cancer but show limited efficacy in wild-type cancers and face resistance issues. To overcome these, we designed novel 6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine-based compounds integrating PARP1 inhibitor pharmacophores with the ATR inhibitor AZD6738 scaffold. Substituent modifications influenced PARP1 and ATR selectivity, yielding dual inhibitors or selective PARP1 inhibitors. Compound 38a, the lead candidate, exhibited potent dual inhibition (IC50 < 20 nM) and strong antitumor effects in MDA-MB-231 (IC50 < 0.048 μM) and MDA-MB-468 (I

Inhibition of MCL-1 and MEK Overcomes MEK Inhibitor Resistance in Triple-Negative and Inflammatory Breast Cancers.

The MAPK pathway can drive resistance in highly aggressive breast cancers. Our previous work showed that the MEK inhibitor (MEKi) AZD6244 (selumetinib) prevented lung metastasis in a breast cancer xenograft model. In clinical studies, MEKis as single agents have had only modest activity against solid tumors due to the onset of resistance. Using synthetic lethality siRNA screening, we identified myeloid cell leukemia-1 (MCL-1) as a potential contributor to AZD6244 resistance. We hypothesized that MCL-1 promotes MEKi resistance in highly aggressive breast cancers and that MCL-1 inhibition overco

Targeting triple-negative breast cancer: apoptotic and antitumor effects of Artemisia sieberi Besser extracts.

Artemisia sieberi Besser (A. sieberi) has shown promise as a natural source of safe cytotoxic agents for breast cancer therapy. However, its … micals and apoptosis-regulating proteins. A. sieberi extracts exhibited higher cytotoxicity against MDA-MB-231 cells than against MCF-7 cells, with lower IC50 values. Treatment of TNBC cells induced apoptosis, evidenced by increased caspase activity, mitochondrial membrane permeabilization, elevated Bax, and decreased Bcl-2 expression. Additionally, colony formati …

Renin angiotensin system inhibition attenuates adipocyte-breast cancer cell interactions.

Obesity is a significant breast cancer (BC) risk factor and is associated with 20-40% increased risk in obese post-menopausal women compared to their lean counterparts. Several obesity-related metabolic dysregulations have been linked to BC risk, including overactivation of the renin-angiotensin system (RAS). Currently, RAS inhibitors including angiotensin converting enzyme inhibitor (ACEi) and AT1 receptor blockers (ARBs), are used as safe and effective anti-hypertensive therapies in BC patients. However, it is uncertain how inhibition of RAS in adipose tissue impacts obesity-BC crosstalk. We

Role of hypoxia and autophagy in MDA-MB-231 invasiveness.

Survival strategies adopted by tumor cells in response to a hypoxic stress include activation of hypoxia-inducible factor 1 (HIF-1) and autophagy. However, the importance and the function of each molecular response is not well defined. In the present study, we investigated invasiveness, migration, matrix metalloproteinases (MMPs) activity, and cell survival of MDA-MB-231 cells under normoxia, hypoxia, and hypoxia/reoxygenation (H/R). Moreover, to assess the importance of hypoxia and autophagy on the parameters studied, cells were either left untreated or treated with Chetomin (a selective inhi…