MCF-7 Breast Cancer Research Articles

To date, breast cancer remains one of the leading causes of death among women worldwide. Although various treatments are used in clinical settings, the efficacy and safety of such treatments are limited by tumor biology factors and patient preferences. Previous studies have shown that triple-negative BRCA1-deficient breast cancer is susceptible to DNA-damaging agents, including platinum-based drugs and poly(ADP-ribose) polymerase (PARP) inhibitors, alone or in combination. To address whether the combinative treatment of these DNA-damaging agents can be extended to the triple-negative BRCA1-proficient breast cancer population, we investigated the anticancer activity of the well-known FDA-approved PARP inhibitor olaparib in combination with the antimetastatic ruthenium(II)–arene PTA compound RAPTA-T for triple-negative BRCA1-competent breast cancer cells (MDA-MB-468 and MDA-MB-231), with consideration of sporadic breast cancer MCF-7 cells. RAPTA-T, olaparib, and the combined agents exhibited a dose-dependent inhibition of breast cancer cell growth in selected breast cancer cells. The combination compound inhibited colony formation most effectively in MDA-MB-468 cells. Additionally, the scratch-wound assay showed that MDA-MB-468 cells migrated more slowly than MCF-7 and MDA-MB-231 cells. The results indicated that the olaparib and RAPTA-T combination can reduce or inhibit the survival, invasion, and metastasis of breast cancer cells. Moreover, the combined agents promoted apoptotic cell death, with a higher percentage of apoptosis observed in MDA-MB-468 cells than in MDA-MB-231 and MCF-7 cells. Olaparib and RAPTA-T also interfered with cell cycle progression, with the greatest inhibition observed in the S and G2/M phases of MCF-7 cells (1.6- and 3.4-fold), followed by MDA-MB-468 cells (1.6- and 1.8-fold) and MDA-MB-231 cells (1.5- and 1.4-fold). Interestingly, MDA-MB-468 cells presented the highest degree of inhibition for BRCA1 replication and BRCA1 expression. The p53, PARP, and Chk1 proteins were more strongly upregulated in MDA-MB-231 cells than in Ru-untreated control cells. Moreover, the expression levels of protein biomarkers associated with the epithelial-to-mesenchymal transition (EMT), including E-cadherin and SLUG, were remarkably reduced in all tested breast cancer cells. Together, our results show the feasibility of extending the application of PARP inhibitors beyond breast cancer with BRCA1 mutations and optimizing the combinative treatment of PARP inhibitors with antimetastasis ruthenium-based chemotherapy as new therapeutic approaches for TNBC harboring wild-type BRCA1.

Therapeutic Potential of Allyl Sulfide-noscapine Hydrochloride Combination-loaded Hollow Mesoporous Silica Nanoparticles in Breast Cancer MCF-7 Cells

Cancer remains a global health concern, demanding the development of new therapeutic medicines. This research focuses on the synthesis, in vitro evaluation, and in silico analysis of new 2-substituted benzothiazole derivatives as possible anticancer drugs. Hybrid molecules comprising benzothiazole and pyridinone rings 8a–c and 10a–c were also synthesized. Several compounds were produced and characterized, using NMR, IR and elemental analysis, with promising anticancer activity against lung H1299, liver Hepg2 and breast MCF7 cancer cell lines. Structure–activity connection investigations identified crucial structural characteristics that influence potency, with benzylidine derivatives 6a–g demonstrating higher activity. In silico ADME research revealed favorable drug-like features for chosen compounds, such as high gastrointestinal absorption and selective CYP inhibition. Toxicological projections indicated few side effects, confirming their potential as medication candidates. Inverse-docking analysis of the five potent compounds 6a–c, 6e, and 6f against 12 selected protein tyrosine kinases (PTKs) and cyclin-dependent kinases (CDKs) revealed good docking scores, strong interaction patterns, and potential inhibitory effects, particularly against ABL1, ABL2, CDK4, and CDK6 enzymes, suggesting these compounds as promising candidates for further drug development.

Promotional effects of aged ZnO nanoparticles on migration, invasion and metastasis of human breast cancer MCF-7 cells in vitro and in vivo

Desmosomes are essential cell-cell adhesion organelles that enable tension-prone tissues, like the skin and heart, to withstand mechanical stress. Desmosomal anomalies are associated with numerous epidermal disorders, cardiomyopathies, and cancer. Despite their critical importance, how desmosomes sense and respond to mechanical stimuli is not understood. Here, we combine super-resolution imaging in epithelial cells and primary cardiomyocytes, FRET-based tension sensors, atomistic computer simulations, and biochemical assays to demonstrate that actomyosin forces induce a conformational change in desmoplakin, a key cytoplasmic desmosomal protein. We show that in human breast cancer MCF7 cells, keratin-19 couples F-actin filaments to desmosomes and regulates the level of actomyosin forces integrated into the desmosomal complex. We demonstrate that actomyosin contractility reorients keratin intermediate filaments and directs force to desmoplakin along the keratin network, plausibly converting the N-terminal plakin domain from a folded to an extended conformation. We also show that desmoplakin undergoes a similar actomyosin force-dependent conformational change in primary cardiomyocytes, with the extent of the change affected by myofibril orientation. Our findings establish that desmoplakin is mechanosensitive and its structural states reflect the level of forces transmitted through the actin network across cell types.

Exopolysaccharides (EPSs) produced by haloalkaliphilic archaea exhibit unique properties contributing to varied industrial and medicinal applications. This study explored the anticancer therapeutic potential of an EPS derived from a haloalkaliphilic archaeal strain, which has not been previously isolated from solar salterns on the northwestern Mediterranean Egyptian coast. The selected isolate was identified as Natrialba chahannaoensis BG8. A Plackett–Burman (PB) fractional factorial design determined NaCl as the only significant variable positively affecting EPS production. The partially purified EPS analytical characterization revealed a carbohydrate content of 75.16 ± 2.1%, with Fourier transform infrared (FT-IR) spectroscopy; moreover, GC–MS suggested a heteropolysaccharide nature. For the first time, a neutral red uptake (NRU) assay revealed the anticancer effect of EPS against multiple human cancerous cell lines; A-431 epidermoid cancer (IC50= 8.8 mg/mL), MCF-7 breast cancer (IC50= 12.7 mg/mL), MDA-MB-231 triple-negative breast cancer (TNBC) (IC50= 9.4 mg/mL), and HCT-116 colorectal cancer (IC50= 10.4 mg/mL) cells. Additionally, EPS exhibited previously reported anti-hepatoblastoma activity against HepG-2 cells (IC50= 21.2 mg/mL). The cell cycle analysis results suggested that the antiproliferative effect on MDA-MB-231 cells occurred through S phase arrest. Notably, synergistic interactions between EPS and the anticancer drug paclitaxel (PXL) were recorded in MDA-MB-231 cells via the Chou‒Talalay approach. Furthermore, an unpaired Student’s t test disclosed that EPS induced a significant rise in the apoptosis marker caspase-3 (casp-3). This increase was higher than PXL alone and combined with EPS. However, the combined treatment exceeded PXL in significantly reducing MDA-MB-231 cells’ migratory potentials, as evidenced by wound healing and matrix metalloproteinase-9 (MMP-9) determination assays. It also reduced the levels of the oxidative stress marker malondialdehyde (MDA). The EPS of N. chahannaoensis BG8 displayed a pro-apoptotic action against the TNBC cells MDA-MB-231, surpassing that of PXL. Furthermore, PXL–EPS combination reduced PXL-associated toxicity and increased metastasis control. These findings put EPS as a recommended safe complementary therapy, more effective than PXL monotherapy.

Breast cancer (BC) is a commonly diagnosed and life-threatening malignancy worldwide. Present study explores the anticancer activity of essential oil (EO) hydrodistilled from the leaves of Syzygium cumini L. Chemical constituents extracted from oil were analysed by Gas-Chromatography Mass Spectrometry (GC-MS). A total of 36 distinct constituents were identified out of 46 present where ocimene (55.48%), β-pinene (8.15%) and α-pinene (7.70%) were observed as the major one. The EO also exhibited antiproliferative activity against two breast cancer cell lines, MDA-MB-231 and MCF-7, yielding an IC50 value of 12.07 µg/mL and 10.30 µg/mL, respectively. Phytoconstituents have shown good binding interaction along with docking scores against ERα (PDB ID-4XI3) which indicates the effectiveness of oil for BC. Pharmacokinetic properties of constituents were also found within the acceptable range.

Early detection of cancer remains a key challenge because current SPR-PCF sensors lack both sensitivity and robust light–analyte interaction. To overcome these limitations, this study proposed and validated an SPR biosensor utilizing MXene-functionalized PCF. By introducing a composite structure of MXene nanomaterials and Au, the detection performance of the sensor was significantly improved. The sensor adopts a circular air hole arrangement and double-groove morphology design and leverages MXene’s high conductivity and gold’s chemical stability to simultaneously enhance plasmonic coupling and biocompatibility. Through FEM-based structural optimization of the air hole diameter, Au layer thickness, and groove shape, the sensor exhibited outstanding refractive-index detection performance with a wavelength sensitivity of 11,072 nm/RIU, an impressive quality factor reaching 201.3 RIU−1, and a resolution as fine as 9.03 × 10−6 RIU. The simulation results demonstrated the capability of the sensor to discriminate six distinct cancer-cell types (cervical cancer HeLa, leukemia Jurkat, pheochromocytoma PC-12, triple-negative breast cancer MDA-MB-231, and breast cancer MCF-7) with high sensitivity and verify its ability to detect pan-cancer species. This study demonstrates an innovative approach for constructing a high-performance SPR sensing platform that has important application potential in the context of the early detection of multiple cancers.

G9a and G9a-like protein (GLP) are histone methyltransferases that regulate epigenetics by adding methyl groups to histone H3, thereby controlling gene expression. G9a/GLP dysregulation and overexpression have been reported to cause cancer proliferation, progression, and metastasis. So far, quinazoline-based inhibitors and degraders have been frequently used as chemical tools to elucidate the role of G9a/GLP. However, quinazoline-based inhibitors exhibit toxicity in normal cells. In this context, we identified a G9a/GLP degrader (4) based on RK-701, a less-toxic G9a/GLP-selective inhibitor. Compound 4 effectively decreased G9a/GLP protein levels and methylated histone levels in breast cancer MCF-7 cells without inhibiting the cell viability, similar to G9a small interfering RNA (siRNA). Furthermore, again similar to G9a siRNA, the degradation of G9a/GLP by 4 inhibited the migration of MCF-7 cells. These results suggest potential for 4 to serve as a valuable tool for investigating the G9a/GLP biology and as a lead compound for drug discovery.

Synthesis and characterization of chitosan Schiff bases conjugated with chalcones for enhanced biological applications.

Doxorubicin (DOX) is an anthracycline derivative, a conversant chemotherapeutic agent, and one of the most influential chemotherapeutic drugs. Long noncoding RNAs (lncRNAs) play a vital role in this process. The current review demonstrates that lncRNAs can function as oncogenic and tumor suppressors and contribute to cancer development and progression. Our study addressed the nuclear-enriched abundant transcript 1 (NEAT1) and the effect of DOX on the regulation of miR410-3p by NEAT1. An MTT assay was conducted to determine the half-maximal inhibitory concentration. The initial step was RNA isolation, which was performed after the cell culture. Then, cDNA synthesis was carried out for both miRNAs and lncRNAs to use RT-PCR to identify changes in RNA expression. Alterations in expression levels were measured by quantitative real-time polymerase chain reaction analyses. This web-based analysis was performed using the Student's t-test. After DOX treatment, NEAT1 expression levels decreased in human breast cancer (BC) cells, including MDA-MB231 and MCF-7. As expected, further expression than in cancer cell lines was detected in the normal mammary epithelial cell line MCF-10A. Simultaneously, miR410-3p expression levels exhibited an increase in BC cells. Our data demonstrated that NEAT1 expression was suppressed in cancer cells treated with doxorubicin, suggesting a potential therapeutic effect. These data indicate that DOX may affect BC lines via NEAT1, and that miR410-3p is effective in this pathway. Our data confirm the contribution of NEAT1 and miR410-3p to DOX treatment. Therefore, they can be used as a biomarker for the diagnosis and treatment of BC.

Characterization of Mg-independent and Mg-dependent Ecto-ATPase activities in luminal a breast cancer MCF-7 cells.

The aim of this study was to investigate the metabolites in Aspergillus subramanianii 1901NT-1.40.2 extract using UPLC-MS, isolate and elucidate the structure of individual compounds, and study the antimicrobial and cytotoxic activities of the isolated compounds. The structures of two previously unreported ergostane triterpenoid aspersubrin A (1) and pyrazine alkaloid ochramide E (2) were established using NMR and HR ESI-MS. The absolute configuration of 1 was determined using quantum chemical calculations. Moreover, the known polyketides sclerolide (3) and sclerin (4); the indolediterpene alkaloid 10,23-dihydro-24,25-dehydroaflavinine (5); the bis-indolyl benzenoid alkaloids kumbicin D (6), asterriquinol D dimethyl ether (7), petromurin C (8); and the cyclopentenedione asterredione (9) were isolated. The effects of compounds 3-9 on the growth and biofilm formation of the yeast-like fungus Candida albicans and the bacteria Staphylococcus aureus and Escherichia coli were investigated. Compounds 5 and 6 inhibited C. albicans growth and biofilm formation at an IC50 of 7–10 µM. Moreover, the effects of compounds 3-9 on non-cancerous H9c2 cardiomyocytes, HaCaT keratinocytes, MCF-10A breast epithelial cells, and breast cancer MCF-7 and MDA-MB-231 cells were also investigated. Compound 8 (10 µM) significantly decreased the viability of MCF-7 cells, inhibited colony formation, and arrested cell cycle progression and proliferation in monolayer culture. Moreover, 8 significantly decreased the area of MCF-7 3D spheroids by approximately 30%. A competitive test with 4-hydroxytamoxyfen and molecular docking showed that estrogen receptors (ERβ more than ERα) were involved in the anticancer effect of petromurin C (8).

To investigate the role of circular RNA circ_0000437 in regulating biological behaviors of breast cancer cells and the molecular mechanism. Breast cancer MCF-7 and MDA-MB-231 cells were transfected with sh-circ_0000437, mimics, inhibitor, si-CTPS1, or their respective negative controls. qRT-PCR was used to detect the expression levels of circ_0000437, let-7b-5p, CTPS1, Notch1, Hes1, and Numb in breast cancer cell lines and tissues. RNase R digestion was used to confirm the circular structure of circ_0000437 and its subcellular localization in the breast cancer cells was determined by cellular distribution analysis. The changes in proliferation, invasion and migration of the transfected cells were assessed using CCK-8 assay, Transwell assay and scratch assay. Dual-luciferase reporter gene and RNA immunoprecipitation assays were employed to validate binding interactions among circ_0000437, let-7b-5p, and CTPS1. The cellular expressions of CTPS1, E-cadherin, N-cadherin, and vimentin proteins were detected with Western blotting. A tumor-bearing mouse model was used to verify the oncogenic mechanism of circ_0000437 and CTPS1. Circ_0000437 and CTPS1 were upregulated while let-7b-5p was downregulated in breast cancer tissues and cell lines. Circ_0000437 or CTPS1 knockdown obviously suppressed breast cancer cell proliferation, invasion, migration and epithelial-mesenchymal transition (EMT). Overexpression of let-7b-5p produced similar inhibitory effects, whereas inhibition of let-7b-5p significantly enhanced malignant behaviors of the cells. In the tumor-bearing mouse models, circ_0000437 knockdown significantly suppressed tumor growth, but co-transfection of the cells with pcDNA-CTPS1 accelerated tumor growth. Binding sites were identified between circ_0000437 and let-7b-5p and between let-7b-5p and CTPS1, and circ_0000437, let-7b-5p, and CTPS1 showed functional interactions in breast cancer cells. Circ_0000437 is upregulated in breast cancer tissues and cells, and its high expression promotes proliferation, invasion, migration and EMT of breast cancer cells through the let-7b-5p/CTPS1 axis.

Hydrazono­[1,3,4]­thiadiazoles have a prominent positionamong theheterocyclic compounds due to their broadening aspects of biologicalactivities. In the current study, a neoteric series of [1,3,4]­thiadiazolestethered to alkoxyaryl hydrazone has been formulated via the treatmentof methyl 2-[3-(pentyloxy)­benzylidene]­hydrazine-1-carbodithioate andhydrazonoyl chlorides in ethanolic solution under thermal conditions.DABCO, as an environmentally nontoxic material, was utilized as asuperior basic catalyst for the latter reaction. The structures ofthe isolated products were explicated by spectral (IR, NMR, and MS)and elemental analysis tools. The antitumor activity of the synthesizedproducts was assessed against the breast cancer MCF-7 cell line. Theresults displayed that compounds 5a and 5f have highly selective inhibition profiles related to doxorubicinas a reference drug. The molecular docking analysis was performedusing the Molecular Operating Environment (MOE) software through theinteraction with the VEGFR-2 protein (PDB: 2OH4) and revealed that compounds 5a and 5f are linked with the same amino acid (GLU883),similar to the reference antibiotic doxorubicin. Also, these compoundsexhibited higher binding affinities (−7.86 and −8.47kcal/mol, respectively) than the reference compound (−6.68kcal/mol), which supported their antitumor efficacy against the MCF-7cell line. Moreover, confirmation of the drug-like properties andtoxicity predictions of the newly synthesized compounds (5a–m) was achieved via in silico ADME.

Damnacanthal exerts anti-cancer effects in breast cancer cells via NAG-1 upregulation, CRM1 downregulation, and induction of autophagy.

Breast cancer ranks as one of the most prevalent cancers impacting women worldwide, posing significant treatment challenges due to chemotherapy resistance and high recurrence rates. This study investigates the therapeutic potential of Dendrosomal Nanocurcumin (DNC), a novel formulation aimed at enhancing curcumin's bioavailability. The focus is on its impact on the Wnt/β-catenin signaling pathway via the modulation of the PIWIL2 protein in MCF-7 breast cancer cells.The Wnt/β-catenin signaling pathway is crucial for controlling cell proliferation, differentiation, and apoptosis. Its dysregulation is strongly linked to breast cancer progression. PIWIL2, a member of the PIWI subfamily of Argonaute proteins, plays a role in RNA silencing, DNA methylation, histone modification, gene transcription regulation, and interactions with oncogenic pathways. These functions highlight its importance in gene regulation, stem cell maintenance, and cancer progression.In this study, MCF-7 cells were treated with Dendrosomal Nanocurcumin at a dose of 20µM for 48 h, based on the IC50 determined from the MTT assay. Real-time PCR analysis revealed that DNC treatment significantly reduced the expression levels of β-catenin (p < 0.0001), Cyclin D1 (p < 0.0001), and PIWIL2 (p < 0.00001), while significantly increasing the expression of GSK3β (p < 0.0001).These findings were supported by Western blot analysis, which showed a significant decline in both phosphorylated and non-phosphorylated forms of β-catenin and PIWIL2 proteins. This suggests that DNC disrupts the Wnt/β-catenin signaling pathway by reducing the stability and cytoplasmic accumulation of β-catenin. The reduction in β-catenin likely prevents its nuclear translocation and the subsequent activation of target genes like Cyclin D1, thus inhibiting cell proliferation and promoting apoptosis. Furthermore, a significant decrease in PIWIL2 protein levels in DNC-treated cells indicates that DNC targets PIWIL2, further inhibiting the Wnt/β-catenin signaling pathway and reducing the oncogenic potential of MCF-7 breast cancer cells.These findings highlight the potential of DNC as an effective treatment option for breast cancer, particularly in overcoming resistance to conventional therapies. Further research is necessary to gain a comprehensive understanding the mechanisms of DNC and its clinical efficacy, offering hope for enhanced breast cancer treatment strategies.

Reactive oxygen species (ROS) are by-products of cellular aerobic metabolism, playing a crucial role in the development of multiple diseases, such as cancer. ROS are generated by various enzymes, including respiratory complexes such as respiratory complex III (a.k.a. bc1 complex), which encompasses four redox centers (Fe2S2, heme bL, heme bH, and heme c1) and two native binding sites (Qo and Qi sites). In the current study, we explored a novel anti-cancer mechanism by binding electron tunneling (ET)-modulating agents at the newly discovered Non-Q or NQ site in the bc1 complex, thereby controlling the conformation of a key phenylalanine 90 (Phe90) residue, which acts as an internal ET switch between heme bL and heme bH. Our proposed mechanism would potentially enhance or reduce ET between heme bL and heme bH, ultimately reducing or increasing the cellular ROS levels. To explore our proposed mechanism, we performed extensive virtual screening of 1,489,806 ligands from the ZINC20 database against the Qo, Qi, and NQ sites of the bc1 complex, obtaining 272 patented ligands that bind preferentially at the NQ site compared to the Qo and Qi sites. Biochemical assays for the top hit ligands, examining their ROS-regulatory and cytotoxic activities against breast cancer MCF7 cells, led to the discovery of potential compounds that upregulate and downregulate ROS. We found significant cytotoxic activity for the single treatment of a lead-hit ROS upregulator and even more synergistic cytotoxic activity for the sequential treatment of ROS upregulator and ROS downregulator ligands, which could be reserved for more resistant cancer cells.

To evaluate the inhibitory effect of Macrothele raveni crude venom against proliferation of different cancer cells and identify the active components in the venom. Different cancer cell lines were treated with different concentrations of Macrothele raveni venom for 48 h, and cell proliferation and the half-maximal inhibitory concentrations (IC50) of the venom were assessed with CCK-8 assay. The apoptosis rate of breast cancer MCF7 cells following the treatment was analyzed with flow cytometry, and the changes in cellular caspase-8 and caspase-9 expressions were detected. The crude venom was separated into protein, peptide, and small-molecule compound fractions using gel filtration chromatography and high-performance liquid chromatography (HPLC). The protein and peptide components were identified using proteomics analysis, and small-molecule compounds were structurally characterized using nuclear magnetic resonance (NMR), mass spectrometry (MS), and HPLC. The crude venom exhibited strong concentration-dependent inhibitory effects on proliferation of MCF7 cells and nasopharyngeal carcinoma SUNE1 and HONE1 cells (IC50 of 2.14±0.29, 1.57±0.14, and 2.85±0.15 µg/mL, respectively), with less potent inhibitory effects in gastric cancer HGC27 cells and colorectal cancer SW620 cells (IC50 of 3.02±0.27 and 3.02±0.28 µg/mL, respectively). The crude venom significantly promoted MCF7 cell apoptosis likely via the caspase 8 signaling pathway. The protein fraction from the crude venom showed a weak inhibitory effect in MCF7 cells, whereas the peptide fraction exhibited a much stronger inhibitory effect (IC50 of 6.41±0.31 µg/mL). The peptides in the peptide fraction, with relative molecular mass around 10 000, were homologous to those found in Macrothele gigas venom. The small-molecule fraction consisted mainly of nucleotide metabolites without obvious inhibitory effects in MCF7 cells, but its combination with the peptide fraction showed significantly enhanced inhibitory activity. Conclusion The inhibitory effects of Macrothele raveni venom, which vary significantly across different cancer cell lines, are attributed primarily to its peptide components, which may act synergistically with the nucleotide metabolites.

The role of G-quadruplexes (G4s) in gene regulation has been widely documented, especially in gene promoters. However, the transcriptional mechanisms involving G4s in other regulatory regions remain largely unexplored. In this study, we integrated the G4-DNA data derived from 22 breast cancer patient-derived tumor xenograft (PDTX) models and MCF7 cell line as potential breast cancer-associated G4s (BC-G4s). Genome-wide analysis showed that BC-G4s are more prevalent in gene promoters and the first introns. The genes accommodating promoter or intronic BC-G4s show significantly higher transcriptional output than their non-G4 counterparts. The biased distribution of BC-G4s in close proximity to the transcription start site (TSS) is associated with an enrichment of transcription factor (TF) interactions. A significant negative correlation was detected between the G4–TF interactions within the first introns and their cognate promoters. These different interactions are complementary rather than redundant. Furthermore, the differentially expressed genes (DEGs) harboring promoter and first intron BC-G4s are significantly enriched in the cell cycle pathway. Notably, promoter BC-G4s of DEGs could be a central hub for TF–TF co-occurrence. Our analysis also revealed that G4-related single nucleotide variants (SNVs) affect the stability of G4 structures and the transcription of disease-related genes. Collectively, our results shed light on how BC-G4s within promoters and first introns regulate gene expression and reinforce the critical role of G4s and G4-related genes in breast cancer-associated processes.