MCF-7 Human Breast Cancer Cells Research Articles

Metal-Coordinated Histidine-Functionalized Redox-Responsive Polyethyleneimine as a Smart Gene Delivery Vector.

Despite significant advancements in gene delivery and CRISPR technology, several challenges remain. Chief among these are overcoming serum inhibition and achieving high transfection efficiency with minimal cytotoxicity. To address these issues, there is a need for novel vectors that exhibit lower toxicity, maintain stability in serum-rich environments, and effectively deliver plasmids of various sizes across diverse cell types. In this study, to convert common polyethylenimine (PEI1.8k) into high-performance DNA delivery vectors, an innovative multifunctional vector was constructed based on histidine linked to PEI1.8k by redox-responsive disulfide bonds. Apart from highly efficient transfection of both small and large plasmids into HEK 293T (Human Embryonic Kidney 293T cells) with negligible cytotoxicity, PEI1.8k-S-S-His showed great transfection potential even at low plasmid doses (0.5µg), as well as at serum concentrations ranging from 5 to 30% into HEK 293T cells, and achieved excellent plasmid transfection into NIH/3T3 (Mouse Embryonic Fibroblast cells), and MCF7 (Human Breast Cancer cells). Additionally, several metals were tested (Co, Cu, Cd, Ni, Zn, and Mn) to promote the plasmid packaging functionality and improve transfection efficiency. We observed that, in comparison to PEI1.8k-S-S-His, the manganese-functionalized nanocarrier (PEI1.8k-S-S-His-Mn) could transfect a large plasmid with equal efficiency (~ 30%) into MSCs (Mesenchymal Stem Cells). Interestingly, PEI1.8k-S-S-His-Mn showed higher transfection efficiency with the small plasmid (~ 90%) and the large one (~ 80%) into HEK 293T cells, even better than its backbone. We propose that the presence of metal-coordinated His ligand, redox-responsive S-S bonds, and the cationic polymer can synergistically provide robust DNA binding, efficient endosomal disruption, tolerance of serum protein adsorption, and low cytotoxicity. These new vectors could be promising for gene delivery and may be therapeutically relevant.

Optimized microwave-assisted extraction and characterization of spray dried Luffa aegyptiaca nanomucilage: Physicochemical properties, biological activities, and anticancer efficacy against MCF-7 human breast cancer cells.

Microwave-assisted extraction conditions were optimized using response surface methodology to evaluate the effects of extraction parameters on the yield and carbohydrate content of Luffa aegyptiaca mucilage. Extraction at 540 W for 2 min with a 1:20 (g/mL) was determined as the optimal parameter, resulting in a maximum yield of 5.90 % (w/w) with 63 % carbohydrate content consisting of glucose, galactose, maltose, mannose, and galacturonic acid, with structural linkages of β (1 → 4) and β (1 → 6) glycosidic bonds. The nanomucilage exhibited a monomodal particle size distribution of 145.3 ± 4.60 nm, high thermal stability (-1363.08 J/g), oil and water retention capacity, emulsifying ability (93.06 ± 0.48 %), emulsifying stability (75.02 ± 0.96 %), solubility (95.36 ± 0.89 %), and foaming ability (93.06 ± 0.48 %). Mucilage demonstrated potential in vitro anti-oxidant activity (2.05 ± 0.10 %) against Caco-2 cells, anti-inflammatory activity during membrane stabilization (30.47 ± 0.42 % to 70.46 ± 0.31 %,) and protein denaturation (20.47 ± 0.42 % to 78.39 ± 0.40 %) assays and anticancer activity against human breast cancer cells (MCF-7), with growth inhibition of 100.5 ± 12.45 %. Hence, this evaluation of Luffa aegyptiaca nanomucilage highlights its potential as a multifunctional biomaterial with significant applications in the healthcare industry.

Comparative bioactivity analysis of latex and water extract of Euphorbia gaillardotii: chemical profile, antioxidant capacity, effects on water quality, in vitro antimicrobial-cytotoxic activities, and in silico molecular docking studies.

The genus Euphorbia, belonging to the family Euphorbiaceae, represents a significant ethnobotanical heritage due to the diverse bioactive properties exhibited. In this study, the phytochemical composition and biological activities of latex and aerial parts of the water extract of Euphorbia gaillardotii were investigated. Phytochemical analyses were performed using gas chromatography-mass spectrometry and high-performance liquid chromatography techniques and total antioxidants, phenolics, sugars, organic acids, and aroma components were quantitatively determined. The effects of the test compounds on physicochemical parameters in aqueous media were evaluated by electrical conductivity, dissolved oxygen concentration, and pH measurements. Antimicrobial activity was evaluated on Gram-positive and Gram-negative bacteria and yeast strains using the disk diffusion method. The cytotoxic activity on the MCF-7 human breast cancer cell line was measured spectrophotometrically using the Cell Counting Kit-8 proliferation/apoptosis detection kit. The results showed that E. gaillardotii latex and aerial parts water extract significantly affected the physicochemical parameters of aqueous media, especially at high concentrations. The test substances displayed antimicrobial activity, with the latex-impregnated disks demonstrating larger inhibition zones than the aerial parts extract. The results showed that both the latex and extract treatments exhibited concentration-dependent effects on MCF-7 cell viability (P < 0.001). Furthermore, in silico docking analyses revealed a robust binding affinity of succinic acid, the most prevalent bioactive compound in the extract, towards the B-cell lymphoma 2 (Bcl-2) molecule, with a binding energy of -6.16 kcal/mol. This may be associated with the observed cytotoxicity. These results suggest that E. gaillardotii may be a valuable source for potential pharmacological applications.

Synthesis and exploration of anticancer potential of spirocyclic 1,2,3-triazoline and aziridine derivatives of natural eudesmanolide isoalantolactone.

Eudesmane-type sesquiterpene lactone isoalantolactone 1 is of great interest due to its availability, biological activity and synthetic application. Respective series of original spirocyclic (11S,5') (1,2,3-triazoline-eudesma-4,15-enolides) and (11S)-aziridine-eudesma-4,15-enolides were efficiently synthesized via a chemoselective 1,3-dipolar cycloaddition reaction of organic azides to the exocyclic double bond of the lactone ring of isoalantolactone or 13E-(aryl)isoalantolactones by heating in DMF or toluene. The thermal reactions of isoalantolactone with benzyl azide, 2-azidoethanol, or n-butyl azide in 2-methoxyethanol afforded 13-(alkyamino)isoalantolactones formed as a mixture of (Z) and (E)-isomers. The results of in vitro biological assays showed that novel spirocyclic isoalantolactone derivatives exhibited cytotoxicity against human breast cancer and glioblastoma cells at low micromolar concentrations. The most cytotoxic and selective (11S,5')-spiro-1,2,3-triazoline from 13E-(fluorophenyl)isoalantolactone 20 (IC50(MCF-7)=8±0.1µM, SI(MCF-7)>12.5) was found to induce ROS-dependent death of MCF-7 human breast cancer cells via mitochondrial apoptosis. The corresponding (11S)-spiroaziridine derivatives 21 at non-toxic concentrations (10 and 20µM) effectively suppressed motility, clonogenicity and adhesion of glioblastoma cells and exhibited synergistic cytotoxicity in combination with temozolomide. In silico analysis revealed the potential ability of the 13-aryl (11S)-spiroaziridine derivative 21 to bypass the blood-brain barrier and exhibit anti-glioblastoma activity probably based on the direct interaction with Hsp90α.

Synthesis and anti-tumor activity of menthylamine derivatives: Focusing on the potent inhibitory effect of compound W8 on glioma growth

In this work, we successfully synthesized eight distinct compounds, comprising four chiral menthylamines and related derivatives. We evaluated their cytotoxic potential against a panel of human cancer cell lines, including human colon cancer HCT-116 cells, human esophageal squamous KYSE-150 cells, human breast cancer MCF-7 cells, and human glioma U87 cells. The U87 cells were chosen for a more in-depth investigation of their anti-tumor efficacy. Further exploration of the cytotoxicity mechanisms was conducted, complemented by in vivo studies using mice bearing tumors. These analyses unveiled the possible mechanisms by which menthylamide derivatives exert their anti-tumor effects. Notably, compound W8 demonstrated a potent inhibitory action against the proliferation of brain glioma cells. The findings from this research provide valuable insights that pave the way for the future application of menthylamides in cancer therapeutics.

Partial Inhibition of Epithelial-to-Mesenchymal Transition (EMT) Phenotypes by Placenta-Derived DBMSCs in Human Breast Cancer Cell Lines, In Vitro.

Stem cell-based therapies hold significant potential for cancer treatment due to their unique properties, including migration toward tumor niche, secretion of bioactive molecules, and immunosuppression. Mesenchymal stem cells (MSCs) from adult tissues can inhibit tumor progression, angiogenesis, and apoptosis of cancer cells. We have previously reported the isolation and characterization of placenta-derived decidua basalis mesenchymal stem cells (DBMSCs), which demonstrated higher levels of pro-migratory and anti-apoptotic genes, indicating potential anti-cancer effects. In this study, we analyzed the anti-cancer effects of DBMSCs on human breast cancer cell lines MDA231 and MCF7, with MCF 10A used as control. We also investigated how these cancer cells lines affect the functional competence of DBMSCs. By co-culturing DBMSCs with cancer cells, we analyzed changes in functions of both cell types, as well as alterations in their genomic and proteomic profile. Our results showed that treatment with DBMSCs significantly reduced the functionality of MDA231 and MCF7 cells, while MCF 10A cells remained unaffected. DBMSC treatment decreased epithelial-to-mesenchymal transition (EMT)-related protein levels in MDA231 cells and modulated expression of other cancer-related genes in MDA231 and MCF7 cells. Although cancer cells reduced DBMSC proliferation, they increased their expression of anti-apoptotic genes. These findings suggest that DBMSCs can inhibit EMT-related proteins and reduce the invasive characteristics of MDA231 and MCF7 breast cancer cells, highlighting their potential as candidates for cell-based cancer therapies.

Synthesis and Characterization of Novel Co(III)/Ru(II) Heterobimetallic Complexes as Hypoxia-Activated Iron-Sequestering Anticancer Prodrugs.

Heterobimetallic complexes of an ambidentate deferiprone derivative, 3-hydroxy-2-methyl-1-(3-((pyridin-2-ylmethyl)amino)propyl)pyridin-4(1H)-one (PyPropHpH), incorporating an octahedral [Co(4N)]3+ (4N = tris(2-aminoethyl)amine (tren) or tris(2-pyridylmethyl)amine (tpa)) and a half-sandwich type [(η6-p-cym)Ru]2+ (p-cym = p-cymene) entity have been synthesized and characterized by various analytical techniques. The reaction between PyPropHpH and [Co(4N)Cl]Cl2 resulted in the exclusive (O,O) coordination of the ligand to Co(III) yielding [Co(tren)PyPropHp](PF6)2 (1) and [Co(tpa)PyPropHp](PF6)2 (2). This binding mode was further supported by the molecular structure of [Co(tpa)PyPropHp]2(ClO4)3(OH)·6H2O (5) and [Co(tren)PyPropHpH]Cl(PF6)2·2H2O·C2H5OH (6), respectively, obtained via the slow evaporation of the appropriate reaction mixtures and analyzed using X-ray crystallography. Subsequent treatment of 1 or 2 with [Ru(η6-p-cym)Cl2]2 in a one-pot reaction afforded the corresponding heterobimetallic complexes, [Co(tren)PyPropHp(η6-p-cym)RuCl](PF6)3 (3) and [Co(tpa)PyPropHp(η6-p-cym)RuCl](PF6)3 (4), in which the piano-stool Ru core is coordinated by the (N,N) chelating set of the ligand. Cyclic voltammetric measurements revealed that the tpa complexes can be reduced at less negative potentials, suggesting their capability to be bioreductively activated under hypoxia (1% O2). Hypoxia activation of 2 and 4 was demonstrated by cytotoxicity studies on the MCF-7 human breast cancer cell line. PyPropHpH was shown to be a typical iron-chelating anticancer agent, raising the mRNA levels of TfR1, Ndrg1 and p21. Further qRT-PCR studies provided unambiguous evidence for the bioreduction of 2 after 72 h incubation under hypoxia, in which the characteristic gene induction profile caused by the liberated iron-sequestering PyPropHpH was observed.

Non-Invasive Nanometer Resolution Assessment of Cell-Soft Hydrogel System Mechanical Properties by Scanning Ion Conductance Microscopy.

Biomimetic hydrogels have garnered increased interest due to their considerable potential for use in various fields, such as tissue engineering, 3D cell cultivation, and drug delivery. The primary challenge for applying hydrogels in tissue engineering is accurately evaluating their mechanical characteristics. In this context, we propose a method using scanning ion conductance microscopy (SICM) to determine the rigidity of living human breast cancer cells MCF-7 cells grown on a soft, self-assembled Fmoc-FF peptide hydrogel. Moreover, it is demonstrated that the map of Young's modulus distribution obtained by the SICM method allows for determining the core location. The Young's modules for MCF-7 cells decrease with the substrate stiffening, with values of 1050 Pa, 835 Pa, and 600 Pa measured on a Petri dish, Fmoc-FF hydrogel, and Fmoc-FF/chitosan hydrogel, respectively. A comparative analysis of the SICM results and the data obtained by atomic force microscopy was in good agreement, allowing for the use of a composite cell-substrate model (CoCS) to evaluate the 'soft substrate effect'. Using the CoCS model allowed us to conclude that the MCF-7 softening was due to the cells' mechanical properties variations due to cytoskeletal changes. This research provides immediate insights into changes in cell mechanical properties resulting from different soft scaffold substrates.

Salicin-Loaded Polyvinyl Alcohol– and Eudragit® E–Based Nanocarriers to Improve Anticancer Activity Against Human MCF-7 Breast Cancer Cells

Salicin-Loaded Polyvinyl Alcohol– and Eudragit® E–Based Nanocarriers to Improve Anticancer Activity Against Human MCF-7 Breast Cancer Cells

Effects of autophagy on the selective death of human breast cancer cells exposed to plasma-activated Ringer’s lactate solution

Plasma-activated Ringer’s lactate (PAL) solution prepared by irradiating an intravenous solution with a non-equilibrium atmospheric pressure plasma is a potential new cancer therapy having no side effects. However, the induction of autophagy to avoid cell death has been confirmed to occur following exposure to PAL solution. It is thought that the antitumor effect of PAL solution could be weakened by this process, which is meant to maintain homeostasis in cells and assists tumorigenesis. Thus, it would be helpful to devise PAL-based cancer therapies that inhibit autophagy. Unfortunately, it is not yet clear which substances in PAL solution promote autophagy. The present work examined the mechanism by which PAL solution induces autophagy when treating MCF-7 human breast cancer cells. Autophagy was found to be temporarily induced upon exposure to PAL solution, suggesting that this effect contributes to cell proliferation. Although autophagy is associated with reactive oxygen and nitrogen species and/or acidic environments, in this study, significant autophagy was observed using a PAL solution diluted 1/256x without these stressors. Acetate, glyoxylate and 2,3-dimethyltartrate in the PAL solution were determined to promote autophagy. Interestingly, 2,3-dimethyltartrate was found to either induce cell death or autophagy depending on the concentration.

Augmentation of cytotoxicity and apoptotic activity in human breast cancer MCF-7 cells by Saussurea costus (Falc.) Lipsch roots

Augmentation of cytotoxicity and apoptotic activity in human breast cancer MCF-7 cells by Saussurea costus (Falc.) Lipsch roots

Kinetics and Optimization Studies of Controlled 5-Fluorouracil Release from Graphene Oxide Incorporated Vegetable Oil-Based Polyurethane Composite Film.

The current study focuses on investigating the potential of produced graphene oxide (GO)/oil-based polyurethane composite films as a drug carrier for 5-fluorouracil (5-FU). Polyurethane was synthesized starting from blends of castor oil and sunflower oil-based glyceride, followed by GO and 5-FU anticancer drug bearing film production by solution casting. GO/PU composite film samples were characterized by FTIR, TGA and SEM analysis, confirming the PU production and distribution of 5-FU drug at a homogeneous level in GO/PU films. Experimental design studies were carried out to provide insight into the influence of GO incorporation, the amount of loaded drug, and the release medium pH value on 5-FU release behavior. The amount of 5-FU delivered from GO/PU composites displayed a tendency to increase at high GO ratios and high pH values, with the obtained maximum ratio of 91.4%. From release kinetics studies, the pH-sensitive behavior of GO/PU composites was observed following a Higuchi or zero-order kinetic model depending on the GO ratio, indicating a sustained release of the drug. The in vitro cytotoxicity effect of GO/PU film through 5-FU drug release was confirmed against the MCF-7 human breast cancer cell line, while good biocompatibility of the drug-free GO/PU film against the L-929 mouse fibroblast cell line was confirmed via MTT assay test. Overall, the findings support that produced GO/PU composites hold potential for clinical drug delivery applications as a 5-FU drug carrier.

Brief Magnetic Field Exposure Stimulates Doxorubicin Uptake into Breast Cancer Cells in Association with TRPC1 Expression: A Precision Oncology Methodology to Enhance Chemotherapeutic Outcome.

Background/Objectives: Doxorubicin (DOX) is commonly used as a chemotherapeutic agent for the treatment of breast cancer. Nonetheless, its systemic delivery via intravenous injection and toxicity towards healthy tissues commonly result in a broad range of detrimental side effects. Breast cancer severity was previously shown to be correlated with TRPC1 channel expression that conferred upon it enhanced vulnerability to pulsed electromagnetic field (PEMF) therapy. PEMF therapy was also previously shown to enhance breast cancer cell vulnerability to DOX in vitro and in vivo that correlated with TRPC1 expression and mitochondrial respiratory rates. Methods: DOX uptake was assessed by measuring its innate autofluorescence within murine 4T1 or human MCF7 breast cancer cells following magnetic exposure. Cellular vulnerability to doxorubicin uptake was assessed by monitoring mitochondrial activity and cellular DNA content. Results: Here, we demonstrate that 10 min of PEMF exposure could augment DOX uptake into 4T1 and MCF7 breast cancer cells. DOX uptake could be increased by TRPC1 overexpression, whereas inhibiting the activity of TRPC1 channels with SKF-96356 or genetic knockdown, precluded DOX uptake. PEMF exposure enhances DOX-mediated killing of breast cancer cells, reducing the IC50 value of DOX by half, whereas muscle cells, representative of collateral tissues, were less sensitive to PEMF-enhanced DOX-mediated cytotoxicity. Vesicular loading of DOX correlated with TRPC1 expression. Conclusions: This study presents a novel TRPC1-mediated mechanism through which PEMF therapy may enhance DOX cytotoxicity in breast cancer cells, paving the way for the development of localized non-invasive PEMF platforms to improve cancer outcomes with lower systemic levels of DOX.

Synthesis of a Novel 7-Chloroquinoline-Sulphocoumarin Hybrid: Characterization, ADME Profiling and Elucidation of its Antiproliferative and Anti-EMT Potential

In the present study, the annulation of 4,7-dichloroquinoline and sulphocoumarin led to the efficient synthesis of a novel hybrid molecule. Both 4,7-dichloroquinoline and sulphocoumarin are significant due to their distinct pharmacological properties. Quinoline derivatives, such as 4,7-dichloroquinoline, are well-known for their broad spectrum of biological activities, including antimalarial, antibacterial, and anticancer properties. Sulphocoumarin compounds, on the other hand, have been recognised for their enzyme inhibition and antioxidant activities, which contribute to their therapeutic potential. By combining these two pharmacophores, we aimed to harness and enhance their individual therapeutic effects. The synthesised compound 8 was characterised by FT-IR, NMR (1H and 13C), and Mass spectrometry. Additionally, the physicochemical properties of the compound were evaluated through in silico pharmacokinetic analysis. The compound showed notable antiproliferative potential against MCF-7 human breast cancer cells (IC50 = 27.53 ± 0.02 μg/mL). Besides, it reduced MCF-7 cell motility in a concentration-dependent manner. Furthermore, the effect of the hybrid compound on the epithelial-mesenchymal transition (EMT) was evaluated by its ability to modulate MCF-7 cell motility, as well as the expression of major mesenchymal marker genes, such as Vim, Zeb1, Snail, Slug, and TGF-β. The dual action of our synthesized hybrid compound 8 as an anti-proliferative and anti-EMT agent suggests its further characterization in the in vivo models and elucidation of any synergistic activity in combination with established anti-cancer agents.

Bufadienolides from Helleborus foetidus and their cytotoxic properties on MCF-7 breast cancer cells

Twelve bufadienolides and six 19-norbufadienolides were isolated from the aerial parts of Helleborus foetidus. They consist of aglycons and glucosides and include nine previously undescribed compounds and a compound reported for the first time as a genuine natural product. Their structures were established by extensive spectroscopic analysis and the structure and absolute configuration of two previously unreported 3,4-epoxy derivatives were confirmed by single crystal X-ray diffraction analysis. The compounds were tested for their cytotoxicity on MCF-7 human breast cancer cells. They show differential cytotoxic activity with IC50 values in the range of 2.4 nM - >10 μM. The potency of the activity strongly correlates with the presence of a C-19 aldehyde group. The data complement the scientific basis underpinning the use of H. foetidus in anthroposophic medicine for the integrative treatment of cancer.

Enhanced adsorption, anticancer and antibacterial potentials of Pontederia crassipes L. extract mediated ecofriendly synthesized ZnO/biochar nanohybrid

This current study presents a green synthesis approach of ZnO, biochar and ZnO/biochar nanostructures using leaves of Pontederia crassipes L. The green fabricated nanomaterials were investigated using different characterization techniques, including as XRD, UV–Vis, TEM, FE-SEM, EDX, BET/BJH, and FTIR. The fabricated nanomaterials were well crystallized with an average crystallite size of 40 nm (ZnO), 43 nm (biochar), and 48 nm (ZnO/biochar). A coomassie brilliant blue G250 (CBB) and methylene blue (MB) removal study was conducted to optimizing (optimize) the influence of operating factors on the adsorption efficiency. Employing a ZnO/biochar 98 % and 99 % adsorption efficiencies were reached in an optimum condition for CCB and MB, respectively. Adopting ZnO/biochar heterostructure as an anticancer for MCF-7 human breast cancer cells was also evaluated. The MTT assay revealed that ZnO/biochar samples exhibit a promise in vitro cytotoxic efficacy against the MCF-7 cell line with IC50 being 79.82 μg /mL. In addition, antimicrobial activity of ZnO/biochar nanoparticles was evaluated on Gram-negative and Gram-positive bacteria. Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were used as test microorganisms. The results revealed that the ZnO/biochar possesses an antibacterial inhibition zone of 11 and 9 mm on E. coli, and S. aureus, respectively.

Naturally Occurring Flavonol, Quercetagetin 5,6,7,3',4'-Pentamethyl Ether (Marionol), as a Nontoxic Plant-Based Fluorescent Probe for Rapid, Sensitive, and Selective Detection of Cu2+ in Water.

Herein, we report a naturally occurring flavonol, quercetagetin 5,6,7,3',4'-pentamethyl ether (known as marionol), as a nontoxic fluorescent probe for rapid, sensitive, and selective detection of Cu2+ in water. The interaction between marionol and Cu2+ ions is studied by various state-of-the-art spectroscopic techniques such as 1H NMR, UV-vis, fluorescence, and high-resolution mass spectrometry (HRMS). Marionol shows strong fluorescence quenching in the presence of Cu2+, whereas other interfering cations such as Fe3+, Co2+, Al3+, Pb2+, Hg2+, Zn2+, Mg2+, Mn2+, Ca2+, Cu+, Ag+, Na+, and K+ produce negligible changes in fluorescence. The binding stoichiometry between marionol and Cu2+ is found to be 2:1, according to Job's plot and HRMS analyses. The binding constant (K a) of Cu2+ with marionol is calculated to be 2.89 × 109 M-2, and the limit of detection is found to be 0.15 μM. In addition, marionol is further used for the quantification of Cu2+ in natural spring water samples. The good recoveries (92-110% with RSD <5%) and its low toxicity to MCF-7 human breast cancer cells make marionol a unique plant-based fluorescent probe for the detection of Cu2+ ions.

NSDHL contributes to breast cancer stem-like cell maintenance and tumor-initiating capacity through TGF-β/Smad signaling pathway in MCF-7 tumor spheroid

BackgroundNAD(P)-dependent steroid dehydrogenase-like protein (NSDHL), which is involved in breast tumor growth and metastasis, has been implicated in the maintenance of cancer stem cells. However, its role in regulating breast cancer stem-like cells (BCSCs) remains unclear. We have previously reported the clinical significance of NSDHL in patients with estrogen receptor-positive (ER +) breast cancer. This study aimed to elucidate the molecular mechanisms by which NSDHL regulates the capacity of BCSCs in the ER + human breast cancer cell line, MCF-7.MethodsNSDHL knockdown suppressed tumor spheroid formation in MCF-7 human breast cancer cells grown on ultralow-attachment plates. RNA sequencing revealed that NSDHL knockdown induced widespread transcriptional changes in the MCF-7 spheroids. TGF-β signaling pathway was the most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway (fold change ≥ 2, P ≤ 0.05) identified in NSDHL-knockdown MCF-7 spheroids compared with the control. In orthotopic tumor models injected with NSDHL-knockdown MCF-7 spheroids, tumor initiation and growth were strongly suppressed compared with those in the control.ResultsBCSC populations with CD44+/CD24- and CD49f+/EpCAM + phenotypes and high ALDH activity were decreased in NSDHL-knockdown MCF-7 spheroids and xenograft tumors relative to controls, along with decreased secretion of TGF-β1 and 3, phosphorylation of Smad2/3, and expression of SOX2. In RNA-sequencing data from The (TCGA) database, a positive correlation between the expression of NSDHL and SOX2 was found in luminal-type breast cancer specimens (n = 998). Our findings revealed that NSDHL plays an important role in maintaining the BCSC population and tumor-initiating capacity of ER-positive MCF-7 spheroids, suggesting that NSDHL is an attractive therapeutic target for eliminating BCSCs, thus preventing breast cancer initiation and progression.ConclusionsOur findings suggest that NSDHL regulates the BCSC/tumor-initiating cell population in MCF-7 spheroids and xenograft tumors.

Induction of Apoptosis and Antiproliferative Activity of MCF-7 Human Breast Cancer Cells with Sonicated Aqueous Peel Extract of Punica granatum L. (Nimali sp.).

The antioxidant and antiproliferative activities of various parts of the Punica granatum L. fruit (Nimali variety) on MCF-7 human breast cancer cells have been investigated. The analysis of the effect on gene regulation and apoptosis induction compared to different extraction methods, was carried out highlighting the fruit's potential anticancer properties attributed to polyphenol-rich composition. This study analyzed alterations in radical scavenging capacity (RSC), phenol (TPC), and flavonoid contents (FC) of pomegranate fruit parts, and antiproliferative activity towards MCF-7 cancer cells using different extraction methods. Most effective peel extract/s were analyzed for total protein content, nitric oxide production, LDH, and Caspase 3 and 8 activities. RT-qPCR was performed with intact RNA to examine the apoptotic pathway and gene expression, and western blot analysis confirmed the presence of tumor suppressor protein/s. The sonicated peel extract (SPL) exhibited the highest RSC, TPC, and FC. Fermented juice displayed higher RSC, TPC, and FC compared to fresh juice. Sonicated peel extract showed an IC50 value of 130±4.5 μg mL-1 against MCF-7 cells, while VERO (healthy) cells had values >1,000 μg mL-1. Sonication was identified as the most effective extraction method for the antiproliferative activity of pomegranate fruit. The study revealed that SPL induced apoptosis via the p21, p53-dependent, caspase 8 pathways, and caspase 3-independent mechanisms in MCF-7 cells. Findings emphasize the potential therapeutic effects of SPL in the antiproliferative effect of MCF-7 cells by modulating caspase 8, p53, and p21-dependent pathways, without activating caspase 3.

Evaluation of Antioxidant and Breast Cancer Cytotoxicity of Beta vulgaris and Daucus carota Methanol Extracts

Breast cancer is the world's most frequent malignancy among women. Many dietary antioxidants have been shown to help prevent oxidative stress, which has been linked to a variety of diseases, including cancer. Many chronic diseases, such as cancer, can be avoided by eating fruits and vegetables on a regular and balanced basis. The current study's goal is to assess the antioxidant and cytotoxic capabilities of methanolic extracts of Beta vulgaris and Daucus carota against MCF-7 human breast cancer cell lines. Therefore, the aim of the present study was to determine the phytochemical components, antioxidant capacity, total phenolic &amp; flavonoid contents in the methanolic extracts of Beta vulgaris and Daucus carota. Further, MTT assay against breast cancer cell line (MCF-7) was performed for the evaluation of cytotoxic activity. The majority of secondary metabolites were found in both the aqueous and methanolic extracts of Beta vulgaris and Daucus carota. Beta vulgaris and Daucus carota have different total phenolic and flavonoid contents. TLC results showed many spots having different Rf values. Moreover, we observe comparable cytotoxic activity in both the extracts against MCF-7 cell lines. Our results reveal that the methanolic extracts of Beta vulgaris and Daucus carota has effective phytochemical constituents, antioxidant and anticancer activity. The total phenolic and flavonoid contents vary between Beta vulgaris and Daucus carota. Further studies are needed to evaluate the chemopreventive potentials of the Beta vulgaris and Daucus carota extract when used alone or in combination with doxorubicin to mitigate the toxic side-effects of the latter.