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Novel thiazole-based cyanoacrylamide derivatives: DNA cleavage, DNA/BSA binding properties and their anticancer behaviour against colon and breast cancer cells.

A novel series of 2-cyano-3-(pyrazol-4-yl)-N-(thiazol-2-yl)acrylamide derivatives (3a-f) were synthesized using Knoevenagel condensation and … 365 nm was observed, with IC50 values of 23 and 25 µM against HCT116 cells, and 30 and 9 µM against MDA-MB-231 cells for compounds 3b and 3c, respectively. In conclusion, compounds 3b and 3c exhibited remarkable DNA cleavage and cytotoxic activity on illumination at 365 nm which might be associated with free radicals' production in addition to having a good affini …

WDR62 mediates TNFα-dependent JNK activation via TRAF2-MLK3 axis.

The mitogen-activated protein kinases (MAPKs) regulate a variety of cellular processes. The three main MAPK cascades are the extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinase (JNK), and p38 kinases. A typical MAPK cascade is composed of MAP3K-MAP2K-MAPK kinases that are held by scaffold proteins. Scaffolds function to assemble the protein tier and contribute to the specificity and efficacy of signal transmission. WD repeat domain 62 (WDR62) is a JNK scaffold protein, interacting with JNK, MKK7, and several MAP3Ks. The loss of WDR62 in human leads to microcephaly and pachygy

Temperature-Sensitive Gold Nanoparticle-Coated Pluronic-PLL Nanoparticles for Drug Delivery and Chemo-Photothermal Therapy.

UNLABELLED: Gold nanoparticle-coated Pluronic-b-poly(L-lysine) nanoparticles (Pluronic-PLL@Au NPs) were synthesized via an easy one-step met … py and dynamic light scattering. Calcein-AM and MTT assays were used to study the cell viability of MDA-MB-231 cells treated with PTX-loaded Pluronic-PLL@Au NPs, and we then irradiated the cells with NIR light. RESULTS: An obvious temperature response was observed for the Pluronic-PLL@Au NPs. Blood compatibility and in vitro cytotoxicity assays confirmed that the …

Generation of Multicellular Breast Cancer Tumor Spheroids: Comparison of Different Protocols.

Multicellular tumor spheroids are widely used models in tumor research. Because of their three dimensional organization they can simulate av … in the different cell lines. MCF-7 cells formed spheroids under almost all analyzed conditions, and MDA-MB-231 cells under only one protocol (liquid overlay technique, 3.5 % Matrigel), while SK-BR-3 did not under neither condition. Therefore, we outline specific methods and recommend the use of adapted and standardized spheroid generation protocols for each cell l …

Mitochondrial rewiring drives metabolic adaptation to NAD(H) shortage in triple negative breast cancer cells.

Nicotinamide phosphoribosyltransferase (NAMPT) is a key metabolic enzyme in NAD+ synthesis pathways and is found upregulated in several tumors, depicting NAD(H) lowering agents, like the NAMPT inhibitor FK866, as an appealing approach for anticancer therapy. Like other small molecules, FK866 triggers chemoresistance, observed in several cancer cellular models, which can prevent its clinical application. The molecular mechanisms sustaining the acquired of resistance to FK866 were studied in a model of triple negative breast cancer (MDA-MB-231 parental - PAR), exposed to increasing concentration

GLIS1, a novel hypoxia-inducible transcription factor, promotes breast cancer cell motility via activation of WNT5A.

We previously demonstrated that expression of a Krüppel-like zinc finger transcription factor, GLIS1, dramatically increases under hypoxic c … under normoxia, while attenuation was found in the cell invasion assay under hypoxic conditions. In MDA-MB-231 cells expressing exogenous 3xFLAG-tagged GLIS1, GLIS1 attenuated cell proliferation and enhanced cell mobility and invasion capacities under normoxia. In addition, breast cancer cells expressing GLIS1 acquired resistance to irradiation. Whole transcriptom …

Diallyl trisulfide, a chemopreventive agent from Allium vegetables, inhibits alpha-secretases in breast cancer cells.

Breast cancer affects one in eight women throughout the course of their lifetime creating a demand for novel prevention strategies against this disease. The Notch signaling pathway is often aberrantly activated in human malignancies including breast cancer. Alpha secretases, including ADAM (A Disintegrin and Metalloprotease) -10 and -17, are proteases that play a key role in the cleavage of cell surface molecules and subsequent ligand-mediated activation of Notch signaling pathway. High expression levels of ADAM10 and 17 have been clinically associated with a lower disease-free survival in bre

Adapalene inhibits the activity of CD44, a cancer stem cell biomarker in Triple negative breast cancer.

BACKGROUND: One of the crucial steps in the development of tumor metastasis is tumor cell invasion. This stage initiates a sequence of molec … s rather than non-TNBC cells, particularly in the 4T1 model. Interestingly, drug-resistant produced MDA-MB-231 cells exhibited a 298-fold increase in ic50 value in comparison to the parental MDA-MB-231 cells. The findings showed that Adapalene targets CD44, a crucial stemness biomarker, to decrease the stemness traits of drug-resistant cells. CONCLUSION: Overall, …

From Luminal to Triple Negative: 3D Spheroids Reveal Molecular and Phenotypic Differences Across Breast Cancer Subtypes.

Breast cancer is classified into distinct molecular subtypes, including Luminal A, Luminal B, HER2-enriched, Basal-like, and Claudin-low. While traditional studies mostly use 2D cell cultures, 3D models better mimic in vivo tumor conditions. In this study, we generated and characterized 3D spheroids from breast cancer cell lines representing different molecular subtypes. Morphologically, spheroids were either compact (MCF-7/AZ, T47D, BT474, MDA-IBC-3, BT-20, SUM149PT) or loosely adhered (MDA-MB-468, SK-BR-3, MDA-MB-231), while retaining key parental subtype biomarkers. Cell viability decreased

Targeting common denominators of DNA damage tolerance mechanisms as therapeutic strategy to cope with dynamic phenotypic changes in triple-negative breast cancer cells.

Triple negative breast cancer (TNBC) is the most aggressive type of breast cancer with limited treatment options and a propensity towards ch … itized by combining Olaparib with low-dose POLζ-, CHK1-, or RAD51 inhibitor, except for 3D-cultured MDA-MB-231 cells, which may resist Olaparib due to their high ZRANB3 complex formation in the nucleus. These findings identify key DDT pathway components such as POLζ and CHK1 as druggable targets that alone or in combination with Olaparib may overcome chemoresistan …

A Glycyrrhiza Glabra-derived pH/ROS Dual-Responsive Phytomedicine Nanoplatform for Combatting Triple-Negative Breast Cancer via Amplified Mitochondrial Damage.

In this work, we engineered a novel core-shell nanoplatform (TG@GPH) based on glycyrrhizic acid (GL) for enhanced mitochondrial-targeted the … cid outer shell. The TG@GPH micelles exhibited good physiological stability and efficient uptake by MDA-MB-231 cells; however, they dissociated under acidic and elevated ROS conditions due to acid-labile cleavage of boronate ester bonds and ROS-triggered oxidative breakage of carbon-boron bonds, thereby rapidly releasing the TG payload. Thereafter, TG selectively …

Interpenetrating polymer network microspheres based on alginate and thiolated CNF for tumor-triggered localized intratumoral therapy.

Interpenetrating polymer network (IPN) microspheres composed of alginate and thiolated TEMPO-oxidized cellulose nanofibers (Th-TCNF) were de … -controlled behaviour, and flow cytometry (FACS) showed sustained intracellular MIT accumulation in MDA-MB-231 cells, leading to prolonged cytotoxicity. In vivo intratumoral administration in BALB/c nude mice bearing MDA-MB-231 xenografts produced significant tumor suppression with extensive necrosis and apoptosis, without systemic toxicity, verified by Histologic …

Pharmacological inhibition of myostatin effectively ameliorates osteolytic lesions in syngeneic and xenograft breast cancer mouse models.

Breast cancer (BC)-derived bone metastases colonize bone and drive severe bone degradation through complex interactions with bone-resorbing osteoclasts (OCs). Subsequent bone resorption liberates matrix-stored factors, such as TGF-β and calcium, which further stimulate tumor proliferation and exacerbate bone destruction. Myostatin (Mstn), a member of the TGF-β superfamily, is known to enhance OC differentiation and bone resorption in models of musculoskeletal disease; however, its role in BC-associated bone lesions and metastases remains unknown. Here, we demonstrate that bone metastases from

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… To determine whether Mstn and other members of the TGF-β superfamily, along with their respective antagonists, are exclusively expressed in 4T1 and MDA-MB-231 cells, we extended our analysis to a broader panel of human TNBC cell lines. … C OC differentiation in co-cultures of WT BMDMs and MDA-MB-231 cells ( n = 8) treated with anti-myostatin antibody (5 µg/ml). D OC differentiation of WT BMDMs cultured with 10% conditioned medium of MDA-MB-231 BC cells and anti-Mstn antibody ( n = 6). …

Three new platinum complexes containing fluoroquinolones and DMSO: Cytotoxicity and evaluation against drug-resistant tuberculosis.

This work describes the synthesis, characterization and biological evaluation of three platinum complexes of the type [Pt(DMSO)(L)Cl]Cl, in … tin. Flow cytometry analysis revealed that [Pt(DMSO)(spf)Cl]Cl induced late apoptotic cell death in MDA-MB-231 cells.

Wedelolactone inhibits breast cancer-induced osteoclastogenesis by decreasing Akt/mTOR signaling.

The bone is the most common metastatic site of breast cancer. Bone metastasis causes pain, pathologic fractures, and severely reduces the quality of life. Breast cancer causes osteolytic bone metastasis, which is dependent on osteoclast-mediated bone resorption. While current treatments rely on palliative anti-resorptive agents, there is a need to develop a drug based on potential alternative therapies. This study is the first to determine that wedelolactone (WDL), a natural coumarin isolated from plants, can inhibit breast cancer-mediated osteoclastogenesis. Osteoclasts were generated from hu

Targeted Inhibition of Anti-Inflammatory Regulator Nrf2 Results in Breast Cancer Retardation In Vitro and In Vivo.

Nuclear factor erythroid-2 related factor-2 (Nrf2) is an oxidative stress-response transcriptional activator that promotes carcinogenesis through metabolic reprogramming, tumor promoting inflammation, and therapeutic resistance. However, the extension of Nrf2 expression and its involvement in regulation of breast cancer (BC) responses to chemotherapy remain largely unclear. This study determined the expression of Nrf2 in BC tissues (n = 46) and cell lines (MDA-MB-453, MCF-7, MDA-MB-231, MDA-MB-468) with diverse phenotypes. Immunohistochemical (IHC)analysis indicated lower Nrf2 expression in no

Cdc42-interacting protein 4 promotes breast cancer cell invasion and formation of invadopodia through activation of N-WASp.

In the earliest stages of metastasis, breast cancer cells must reorganize the cytoskeleton to affect cell shape change and promote cell inva … a Src-dependent activation site (Y256). CIP4 silencing also impaired the migration and invasion of MDA-MB-231 cells and was associated with decreased formation of invadopodia and gelatin degradation. This study presents a new role for CIP4 in the promotion of migration and invasion of MDA-MB-231 breast cancer cells and establishes the contribution of F-BAR protei …

Fabrication of β-glucan nanocarriers for enhanced encapsulation and delivery of doxorubicin for triple negative breast cancer treatment.

In this study, beta glucan nanoparticles were fabricated and encapsulated with Doxorubicin for an effective drug delivery for triple negativ … between 30-100 nm. FTIR and zeta potential analysis confirmed the loading of Dox. The results over MDA-MB-231 cells showed that Dox loaded beta glucan nanoparticles were effectively internalized and had more cytotoxic activity with respect to free drug.

Nano drug delivery of a new scfv-based immunotoxin by chitosan nanoparticles upgrades its efficiency against breast cancer.

This study aimed to develop a chitosan‑based nano‑delivery system encapsulating the PE38KDEL‑1F12 immunotoxin (NP‑IMX) and to evaluate its biological performance in breast cancer cells. NP‑IMX nanoparticles were synthesized and characterized, followed by in vitro evaluation in EPHA2‑positive MDA‑MB‑231 breast cancer cells and EPHA2‑negative MCF‑10 A normal breast epithelial cells. Cytotoxicity, cellular uptake, apoptosis, cell‑cycle arrest, migration, drug loading and release, and gene expression (VEGF, p21, Bax, and p53) were assessed. In addition, short‑term in vivo toxicity was evaluated in

Evaluation of Postbiotics from Lactiplantibacillus plantarum and Bacillus mojavensis Fermented in Aguamiel on Their Cytotoxic Effect in Breast Cancer Cells, Their In Vivo Effects, and Processing by Spray Drying.

BACKGROUND/OBJECTIVES: Postbiotics derived from beneficial bacteria have emerged as promising bioactive ingredients owing to their enhanced stability, safety, and functional versatility relative to live microorganisms. METHODS: The present study was structured in two complementary stages: (i) biological characterization of liquid microfiltrates obtained from Lactiplantibacillus plantarum and Bacillus mojavensis fermented in aguamiel, and (ii) technological stabilization of these postbiotics through microencapsulation by spray drying, with a view to their potential incorporation into food matr