Search Results (2,504)

The secondary metabolites of the fungus Penicillium thymicola, fumiquinazolines F and G, have antibacterial and antifungal characteristics; however, their potential anti-tumor action against human cancer cells remains unknown. The goal of our study was to determine the biological efficacy of fumiquinazolines F and G on breast and prostate cancer cells. Cancer cell proliferation and migration were monitored in real time using xCELLigence technology and flow cytometry. Alterations in mRNA and protein expression were assessed by RT-qPCR, ELISA, and Western blotting. Our data indicate that fumiquinazolines F and G are more effective in inhibiting breast cancer cell proliferation than prostate cancer cells. Fumiquinazoline F is active against both hormone-dependent epithelial MCF-7 (IC₅₀ 48 μM) and hormone-resistant triple-negative mesenchymal MDA-MB-231 breast cancer cells (IC₅₀ 54.1 μM). The metabolite has low cytotoxicity but slows cell cycle progression. In fumiquinazoline F-treated MDA-MB-231 cells, the levels of proteins implicated in epithelial–mesenchymal transition (EMT) (such as E-cadherin, vimentin, and CD44) fluctuate, resulting in a decrease in cell migratory rate and adhesion to a hyaluronic acid-coated substrate. Thus, fumiquinazolines F and G exhibit anticancer activity by inhibiting EMT, cell proliferation, and migration, hence reverting malignant cells to a less pathogenic phenotype. The compound’s multi-target anticancer profile underscores its potential for further exploration of novel EMT-regulating pathways. Full article

Macrophage-mediated inflammation is known to be involved in the epithelial–mesenchymal transition (EMT) of various types of cancer. This makes macrophage-derived inflammatory factors prime targets for the development of new treatments. This study uncovers the therapeutic potential and action mechanism of DAB-2-28, a small-molecule derived from para-aminobenzoic acid, in the treatment of breast cancer. The luminal MCF-7 and the triple-negative MDA-MB-231 cancer cell lines used in this study represent, respectively, breast cancers in which the differentiation states are related to the epithelial phenotype of the mammary gland and breast cancers expressing a highly aggressive mesenchymal phenotype. In MCF-7 cells, soluble factors from macrophage-conditioned media (CM-MØ) induce a characteristic morphology of mesenchymal cells with an upregulated expression of Snail1, a mesenchymal marker, as opposed to a decrease in the expression of E-cadherin, an epithelial marker. DAB-2-28 does not affect the differential expression of Snail1 and E-cadherin in response to CM-MØ, but negatively impacts other hallmarks of EMT by decreasing invasion and migration capacities, in addition to MMP9 expression and gelatinase activity, in both MCF-7 and MDA-MB-231 cells. Moreover, DAB-2-28 inhibits the phosphorylation of key pro-EMT transcriptional factors, such as NFκB, STAT3, SMAD2, CREB, and/or AKT proteins, in breast cancer cells exposed to different EMT inducers. Overall, our study provides evidence suggesting that inhibition of EMT initiation or maintenance is a key mechanism by which DAB-2-28 can exert anti-tumoral effects in breast cancer cells. Full article

Palindromic antimicrobial peptides (PAMs) constitute versatile scaffolds for the design and optimization of anticancer agents with applications in therapy, diagnosis, and/or monitoring. In the present study, fluorolabeled peptides derived from the palindromic sequence RWQWRWQWR containing fluorescent probes, such as 2-Aminobenzoyl, 5(6)-Carboxyfluorescein, and Rhodamine B, were obtained. RP-HPLC analysis revealed that the palindromic peptide conjugated to Rhodamine B (RhB-RWQWRWQWR) exhibited the presence of isomers, likely corresponding to the open-ring and spiro-lactam forms of the fluorescent probe. This equilibrium is dependent on the peptide sequence, as the RP-HPLC analysis of dimeric peptide (RhB-RRWQWR-hF-KKLG)₂K-Ahx did not reveal the presence of isomers. The antibacterial activity of the fluorescent peptides depends on the probe attached to the sequence and the bacterial strain tested. Notably, some fluorescent peptides showed activity against reference strains as well as sensitive, resistant, and multidrug-resistant clinical isolates of E. coli, S. aureus, and E. faecalis. Fluorolabeled peptides 1-Abz (MIC = 62 µM), RhB-1 (MIC = 62 µM), and Abz-1 (MIC = 31 µM) exhibited significant activity against clinical isolates of E. coli, S. aureus, and E. faecalis, respectively. The RhB-1 (IC₅₀ = 61 µM), Abz-1 (IC₅₀ = 87 µM), and RhB-2 (IC₅₀ = 35 µM) peptides exhibited a rapid, significant, and concentration-dependent cytotoxic effect on HeLa cells, accompanied by morphological changes characteristic of apoptosis. RhB-1 (IC₅₀ = 18 µM) peptide also exhibited significant cytotoxic activity against breast cancer cells MCF-7. These conjugates remain valuable for elucidating the possible mechanisms of action of these novel anticancer peptides. Rhodamine-labeled peptides displayed cytotoxicity comparable to that of their unlabeled analogues, suggesting that cellular internalization constitutes a critical early step in their mechanism of action. These findings suggest that cell death induced by both unlabeled and fluorolabeled peptides proceeds predominantly via apoptosis and is likely contingent upon peptide internalization. Functionalization at the N-terminal end of the palindromic sequence can be evaluated to develop systems for transporting non-protein molecules into cancer cells. Full article

The escalating global challenges of antimicrobial resistance (AMR) and cancer necessitate innovative therapeutic solutions from natural sources. This study investigated the multifaceted therapeutic potential of pigment-enriched plant extracts. We screened diverse plant extracts for antimicrobial and antibiofilm activity against multidrug-resistant bacteria and fungi. Hibiscus sabdariffa emerged as the most promising, demonstrating potent broad-spectrum antimicrobial and significant antibiofilm activity. Sub-inhibitory concentrations of H. sabdariffa robustly downregulated essential bacterial virulence genes and suppressed aflatoxin gene expression. Comprehensive chemical profiling via HPLC identified major anthocyanin glucosides, while GC-MS revealed diverse non-pigment bioactive compounds, including fatty acids and alcohols. Molecular docking suggested favorable interactions of key identified compounds (Cyanidin-3-O-glucoside and 1-Deoxy-d-arabitol) with E. coli outer membrane protein A (OmpA), indicating potential antiadhesive and antimicrobial mechanisms. Furthermore, H. sabdariffa exhibited selective cytotoxicity against MCF-7 breast cancer cells. These findings establish H. sabdariffa pigment-enriched extract as a highly promising, multi-functional source of novel therapeutics, highlighting its potential for simultaneously addressing drug resistance and cancer challenges through an integrated chemical, biological, and computational approach. Full article

Breast cancer (BC) progression appears to be significantly influenced by the diabetic microenvironment, characterised by hyperglycaemia and hyperinsulinemia, though the exact cellular mechanisms remain partly unclear. This study investigated the effects of exposure to supra-physiological levels of glucose and insulin on two distinct BC cell models: hormone-responsive MCF-7 cells and triple-negative MDA-MB-231 cells. To evaluate the effects triggered by high insulin level in different BC cell subtypes, we analysed the activation status of PI3K/AKT and MAPK pathways, cell proliferation, cell distribution in cell cycle phases and cell migration. High insulin level significantly activates the insulin metabolic pathway via AKT phosphorylation in both cell lines while inducing pro-proliferative stimulus and modulation of cell distribution in cell cycle phases only in the hormone-responsive MCF-7 cell line. On the contrary, high-glucose containing medium alone did not modulate proliferation nor further increased it when combined with high insulin level in both the investigated cell lines. However, following insulin treatment, the MAPK pathway remained unaffected, suggesting that the proliferation effects in the MCF-7 cell line are mediated by AKT activation. This linkage was also demonstrated by AKT phosphorylation blockade, driven by the AKT inhibitor MK-2206, which negated the proliferative stimulus. Interestingly, while MDA-MB-231 cells, following chronic hyperinsulinemia exposure, did not exhibit enhanced proliferation, they displayed a marked increase in migratory behaviour. These findings suggest that chronic hyperinsulinemia, but not hyperglycaemia, exerts subtype-specific effects in BC, highlighting the potential of targeting insulin pathways for therapeutic intervention. Full article

Nudibranchs have garnered increasing interest in biomedical research due to their complex chemical defense mechanisms, many of which are derived from their diet, including sponges, cnidarians, tunicates, and algae. Their remarkable ability to sequester dietary toxins and synthesize secondary metabolites positions them as a promising source of biologically active compounds with potential therapeutic applications, particularly in oncology. This study aimed to review and summarize the available literature on the bioactive potential of nudibranch-derived compounds, focusing mainly on their antitumor properties. Although research in this area is still limited, recent studies have identified alkaloids and terpenoids isolated from species such as Dolabella auricularia, Jorunna funebris, Dendrodoris fumata, and members of the genus Phyllidia. These compounds exhibit notable cytotoxic activity against human cancer cell lines, including those from colon (HCT-116, HT-29, SW-480), lung (A549), and breast (MCF7) cancer. These findings suggest that compounds derived from nudibranchs could serve as scaffolds for the development of more effective and selective anticancer therapies. In conclusion, nudibranchs represent a valuable yet underexplored resource for antitumor drug discovery, with significant potential to contribute to the development of novel cancer treatments. Full article

Background/Objectives: Cancer suffers from unresolved therapeutic challenges owing to the lack of targeted therapies and heightened recurrence risk. This study aimed to investigate the new series of hydroxamate by structurally modifying the pharmacophore of vorinostat. Methods: The present work involves the synthesis of 15 differently substituted 2H-1,2,3-triazole-based hydroxamide analogs by employing triazole ring as a cap with varied linker fragments. The compounds were evaluated for their anticancer effect, especially their anti-breast cancer response. Molecular docking and molecular dynamics simulations were conducted to examine binding interactions. Results: Results indicated that among all synthesized hybrids, the molecule VI(i) inhibits the growth of MCF-7 and A-549 cells (GI₅₀ < 10 μg/mL) in an antiproliferative assay. Compound VI(i) was also tested for cytotoxic activity by employing an MTT assay against A549, MCF-7, and MDA-MB-231 cell lines, and the findings indicate its potent anticancer response, especially against MCF-7 cells with IC₅₀ of 60 µg/mL. However, it experiences minimal toxicity towards the normal cell line (HEK-293). Mechanistic studies revealed a dual-pathway activation: first, apoptosis (17.18% of early and 10.22% of late apoptotic cells by annexin V/PI analysis); second, cell cycle arrest at the S and G2/M phases. It also promotes ROS generation in a concentration-dependent manner. The HDAC–inhibitory assay, extended in silico molecular docking, and MD simulation experiments further validated its significant binding affinity towards HDAC 1 and 6 isoforms. DFT and ADMET screening further support the biological proclivity of the title compounds. The notable biological contribution of VI(i) highlights it as a potential candidate, especially against breast cancer cells. Full article

Background/Objectives: Magnetic iron oxide nanoparticles (IONPs), human serum albumin (HSA) and folic acid (FA) are prospective components for hybrid nanosystems for various biomedical applications. The magnetic nanosystems FA-HSA@IONPs (FAMs) containing IONPs, HSA, and FA residue are engineered in the study. Methods: Composition, stability and integrity of the coating, and peroxidase-like activity of FAMs are characterized using UV/Vis spectrophotometry (colorimetric test using o-phenylenediamine (OPD), Bradford protein assay, etc.), spectrofluorimetry, dynamic light scattering (DLS) and electron magnetic resonance (EMR). The selectivity of the FAMs accumulation in cancer cells is analyzed using flow cytometry and confocal laser scanning microscopy. Results: FAMs (d_N~55 nm by DLS) as a drug delivery platform have been administered to cancer cells (human breast adenocarcinoma MCF-7 and MDA-MB-231 cell lines) in vitro. Methylene blue, as a model photosensitizer, has been non-covalently bound to FAMs. An increase in photoinduced cytotoxicity has been found upon excitation of the photosensitizer bound to the coating of FAMs compared to the single photosensitizer at equivalent concentrations. The suitability of the nanosystems for photodynamic therapy has been confirmed. Conclusions: FAMs are able to effectively enter cells with increased folate receptor expression and thus allow antitumor photosensitizers to be delivered to cells without any loss of their in vitro photodynamic efficiency. Therapeutic and diagnostic applications of FAMs in oncology are discussed. Full article

This study investigates the effects of copper nanoparticles (CuNPs) on KRT19 gene expression in four breast cancer cell lines (MDA-MB-231, MDA-MB-468, MCF7, and T47D), representing triple-negative and luminal subtypes. Using cytotoxicity assays, quantitative RT-PCR, and bioinformatics tools (STRING, g:Profiler), we demonstrate subtype-specific, dose-dependent KRT19 suppression, with epithelial-like cell lines showing greater sensitivity. CuNPs, characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM) with a mean size of 179 ± 15 nm, exhibited dose-dependent cytotoxicity. Bioinformatics analyses suggest KRT19′s potential as a biomarker for CuNP-based therapies, pending in vivo and clinical validation. These findings highlight CuNPs’ therapeutic potential and the need for further studies to optimize their application in personalized breast cancer treatment. Full article

EGFR is the most frequently altered driver gene in non-small-cell lung cancer (NSCLC), and its overexpression is also associated with breast cancer. In the present study, we synthesized 18 new compounds (B-1, B-2, B-6, B-7, and BP-1–14). The cytotoxicity of these compounds was evaluated in A549 NSCLC and MCF-7 breast cancer cells, as well as in Jurkat cells and PBMCs (healthy). The most potent compounds were further examined for their ability to induce apoptosis in A549 and MCF-7 cells, as well as their EGFR inhibitory activity. Molecular docking was conducted at the ATP-binding site of EGFR, and key pharmacokinetic and toxicity parameters were predicted in silico. B-2 demonstrated the strongest cytotoxicity against A549 and MCF-7 cells (IC₅₀ = 2.14 ± 0.83 μM and 8.91 ± 1.38 μM, respectively), displaying selective cytotoxicity between Jurkat cells and PBMCs (SI = 23.2). B-2 induced apoptosis in A549 and MCF-7 cells at rates of 16.8% and 4.3%, respectively. B-2 inhibited EGFR by 66% at a 10 μM concentration and showed a strong binding affinity to the ATP-binding site of EGFR. Furthermore, B-2 exhibited drug-like characteristics and was not identified as carcinogenic, genotoxic, or mutagenic. B-2 shows promise as an apoptosis inducer and EGFR inhibitor for future anti-NSCLC and anti-breast cancer research. Full article

This study aimed to investigate the underlying mechanisms by which dandelion extract inhibits the proliferation of breast cancer MDA-MB-231 cells. Dandelion root and leaf extracts were prepared using a heat reflux method and subjected to solvent gradient extraction to obtain fractions with different polarities. MTT assays revealed that the ethyl acetate fraction exhibited the strongest inhibitory effect on cell proliferation. LC-MS analysis identified 12 potential active compounds, including sesquiterpenes such as Isoalantolactone and Artemisinin, which showed significantly lower toxicity toward normal mammary epithelial MCF-10A cells compared to tumor cells (p < 0.01). Mechanistic studies demonstrated that the extract induced apoptosis in a dose-dependent manner, with an apoptosis rate as high as 85.04%, and significantly arrested the cell cycle at the S and G2/M phases. Label-free quantitative proteomics identified 137 differentially expressed proteins (|FC| > 2, p < 0.05). GO enrichment analysis indicated that these proteins were mainly involved in cell cycle regulation and apoptosis. KEGG pathway analysis revealed that the antitumor effects were primarily mediated through the regulation of PI3K-Akt (hsa04151), JAK-STAT (hsa04630), and PPAR (hsa03320) signaling pathways. Moreover, differential proteins such as PI3K, AKT1S1, SIRT6, JAK1, SCD, STAT3, CASP8, STAT2, STAT6, and PAK1 showed strong correlation with the core components of the EA-2 fraction of dandelion. Molecular docking results demonstrated that these active compounds exhibited strong binding affinities with key target proteins such as PI3K and JAK1 (binding energy < −5.0 kcal/mol). This study elucidates the multi-target, multi-pathway synergistic mechanisms by which dandelion extract inhibits breast cancer, providing a theoretical basis for the development of novel antitumor agents. Full article

Marine algae offer environmentally friendly platforms for green nanoparticle synthesis. This study reports the biosynthesis of silver nanoparticles using polysaccharides isolated from the brown alga Chnoospora minima (PAgNPs) and evaluates their therapeutic potential. Fourier Transform Infrared Spectroscopy (FTIR) confirmed algal polysaccharide functional groups. Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and Energy Dispersive X-ray (EDX) analysis characterized the nanoparticles as spherical (~84 nm average size), stable (zeta potential −18.5 mV), and containing elemental silver without nitrogen. The PAgNPs exhibited potent antioxidant activity (~100% DPPH scavenging) and significant antimicrobial efficacy, particularly against Staphylococcus aureus and Candida species. Crucially, PAgNPs displayed potent antiproliferative activity against human lung cancer cells (A549, IC₅₀: 13.59 µg/mL). In contrast, toxicity to normal Vero cells was significantly lower (IC₅₀: 300.2 µg/mL), demonstrating notable cancer cell selectivity (SI 22.1). Moderate activity was observed against MCF-7 breast cancer cells (IC₅₀: 100.7 µg/mL). These results demonstrate that C. minima polysaccharide facilitates the synthesis of biocompatible AgNPs with promising antimicrobial and selective anticancer capabilities, highlighting their potential for further development as nanotherapeutics. Full article

Nucleolin (NCL), an RNA-binding protein which regulates critical cellular processes, is frequently dysregulated in human cancers, including breast cancer, making it an attractive therapeutic target. However, molecular details of the RNA-NCL interaction have not been investigated yet. A tRNA fragment named tRF3E, displaying tumor suppressor roles in breast cancer, was found to bind NCL with high affinity displacing NCL-controlled transcripts. Here, we investigated the determinants and cooperativity of tRF3E-NCL interaction by Electrophoretic Mobility Shift Assays and in silico docking analysis, using wild-type or mutated tRF3E. We found that NCL, through its RNA-binding domains (RBD1–2 and RBD3–4), binds simultaneously two tRF3E molecules, giving rise to an energetically favored complex. Instead, a mutant form of tRF3E (M19–24), in which the NCL recognition element in position 19–24 has been disrupted, contacts NCL exclusively at RBD3–4, causing the loss of cooperativity among RBDs. Importantly, when expressed in MCF7 breast cancer cells, tRF3E significantly reduced cell proliferation and colony formation, confirming its role as tumor suppressor, but tRF3E functional properties were lost when the 19–24 motif was mutated, suggesting that cooperativity among multiple domains is required for the NCL-mediated tRF3E antitumor function. This study sheds light on the dynamic of RNA-NCL interaction and lays the foundations for using tRF3E as a promising NCL-targeted biodrug candidate. Full article

The effects of a methanol extract of Nymphaea odorata (MeNO) rhizomes, its fractions and the active compound (methyl gallate, MeG) were investigated in estrogen receptor-positive (ER+) breast cancer cell lines MCF-7 and T47-D:A18, as well as ER-negative line SKBr3. Cell viability and cytotoxicity were determined using CellTiter-Glo^® 2.0 assays at concentrations ranging from 1 to 100 μg/mL. Caspase activity and apoptosis were determined using Caspase-Glo^® 3/7, Caspase-Glo^® 8, and ApoTox-Glo™ triplex assays, as well as qPCR. Total RNA was isolated from MCF-7 cells treated with MeG. RNA-seq libraries were prepared using a Universal Plus mRNASeq kit, and sequencing was performed on a NovaSeq 6000. MeNO inhibited the growth of MCF-7 cells with an IC₅₀ of 14.1 μg/mL, as well as T47-D:A18 (IC₅₀ of 25.6 μg/mL) and SKBr3 cells (IC₅₀ of 35.5 μg/mL). Bioassay-guided fractionation of MeNO in MCF-7 cells identified the active fraction containing one compound, namely methyl gallate (MeG). MeG had an IC₅₀ of 8.6 μg/mL in MCF-7 cells. Transcriptomic analysis of MeG-treated MCF-7 cells showed differential expression of 10,634 genes, with 5643 upregulated and 4991 downregulated (FDR < 0.05). Ingenuity pathway analysis revealed the involvement of 43 canonical pathways, with the top upregulated pathways including apoptosis, autophagy, and the unfolded protein response pathways. Full article

Background/Objectives: HIF-1α and ERRα are both implicated in breast cancer progression, yet their functional interplay remains poorly understood. This study investigates their molecular crosstalk in the context of hypoxia-induced drug resistance. Methods: MCF-7 (estrogen receptor, ER-positive) spheroids and CoCl₂-treated SK-BR-3 (ER-negative) cells were used to model tumor hypoxia. Protein expression, coimmunoprecipitation, chromatin immunoprecipitation (ChIP), pharmacological inhibition, and siRNA-mediated gene silencing were employed to assess physical and functional interactions. Immunohistochemistry (IHC) on a tissue microarray (TMA) of 168 invasive breast carcinomas was performed to evaluate clinical relevance. Results: ERRα levels remained unchanged under hypoxia, while its coactivator, Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 α (PGC-1α), was upregulated. ERRα physically interacted with HIF-1α and was required for HIF-1 transcriptional activity under hypoxic conditions. ChIP assays showed that ERRα-driven overexpression of Permeability glycoprotein 1 (P-gp) and Vascular Endothelial Growth Factor (VEGF) was mediated by HIF-1α binding to the MDR1 and VEGF promoters. Inhibition or silencing of ERRα reversed P-gp overexpression and restored intracellular doxorubicin. TMA analysis confirmed the clinical correlation between ERRα, HIF-1α, and P-gp expression, highlighting the role of ERRα in hypoxia-induced drug resistance. ERRα expression was independent of ER status, suggesting an estrogen-independent function. Conclusions: This study identifies a novel physical and functional interaction between ERRα and HIF-1α that promotes chemoresistance in hypoxic breast tumors. Targeting ERRα may represent a promising therapeutic strategy to overcome drug resistance in aggressive, ER-independent breast cancer subtypes. Full article