MCF-7 Cells Research Articles

Six pairs of enantiomeric prenylated flavonoids with cytotoxic activities from Epimedium sagittatum Maxim.

In this work, six pairs of undescribed enantiomeric prenylated flavonoids, ( ±)-epimesatines J-O (1a/1b-6a/6b), were isolated from the aerial parts of Epimedium sagittatum Maxim. Their structures and absolute configurations were determined based on spectroscopic data, quantum chemical calculations of electronic circular dichroism (ECD) and 13C NMR, as well as ECD experiments induced by Mo2(OAc)4 and Rh2(OCOCF3)4. The cytotoxicity assay revealed that compounds 1a/1b, 2a/2b, and 4a/4b-6a/6b demonstrated significant inhibitory effects on the viability of human breast cancer cells MCF-7 while exhibiting no obvious toxicity towards human breast epithelial cells MCF-10A. Additionally, these compounds were found to decrease the expression of sphingosine kinase 1 (Sphk1) in MCF-7 cells. Notably, compounds 4a and 5b exhibited IC50 values of 7.45 and 8.97μM, respectively, in MCF-7 cells.

A potential new strategy for BC treatment: NPs containing solanine and evaluation of its anticancer and antimetastatic properties

Solanine has been shown to inhibit cancer by regulating the expression of apoptosis (Bax, Bcl-2) and metastasis (CDH-1, MMP2) genes in various cancer cell types. We synthesized optimized niosome NPs (NPs) with high solubility and capacity for solanine loading. In this study, the cytotoxic, cell cycle inhibitory and apoptotic effects of solanine-loaded niosome NPs (SN-NPs) on MCF-7 were investigated. Thin-layer hydration was used to generate SN-NPs and their features were validated. The pH-dependent solanine release pattern was also examined. Synthesized SN-NPs were evaluated for cytotoxicity against MCF-7 and MCF-10 cell lines using MTT. Primary and secondary apoptosis, necrosis, and cell cycle arrest were measured using flowcytometry. Lastly, q-PCR was used to assess the expression of genes. The NPs had an average size between 50 and 70 nm, with a polydispersity index (PDI) of 0.452. Solanine was effectively incorporated into noisome NPs, as shown by the high encapsulation efficiency of 82.3%±0.24%. After a quick burst at pH 7 and 5, SN-NPs released slowly and sustainedly. The IC50 of solanine-loaded niosomes against MCF-7 cells decreased from 40 mg/100 mL to 10 mg/100 mL (48 h) and 5 mg/100 mL (72 h). After 72 h, SN-NPs caused late apoptosis in 30% of MCF-7 cells and necrosis in 5.06% (p < 0.01). SN-NPs caused 81% of cells to arrest in the G0/G1 phase, with only 12% progressing to G2/M (p < 0.01). Solanine-loaded NPs significantly increased Bax and CDH-1 gene expression in malignant cells compared to free niosomes and free solanine (p < 0.0001). Bcl-2 and MMP2 expression significantly decreased in this group compared to free niosomes and free solanine (p < 0.001). Solanine-containing niosomes showed significant anticancer effects on MCF-7 breast cancer cells, which were supported by apoptosis, cell cycle arrest and regulation of gene expression. The regulated release and precise delivery of solanine using SN-NPs show considerable translational potential. This improved nanocarrier technology may increase the bioavailability and efficacy of solanine, potentially leading to improved clinical outcomes in breast cancer therapy.

Melatonin enhances everolimus efficacy in breast cancer by suppressing mTOR pathway activation and promoting apoptosis and mitochondrial function

BackgroundEverolimus is used in the treatment of breast cancer by targeting the PI3K/AKT/mTOR pathway, particularly during anti-hormonal therapy. The efficacy of everolimus is limited due to a feedback loop that supresses mTOR while simultaneously enhancing Akt activation in endocrine-resistant breast cancer. Melatonin (N-acetyl-5-methoxytryptamine) regulates mitochondrial activity, cell death, and autophagy due to its strong free radical scavenging, antioxidant, and anti-inflammatory characteristics. Melatonin, a naturally occurring oncostatic agent, slows tumor growth in a range of malignancies, including breast cancer. Due to its ability to protect healthy cells from oxidative stress and inflammation, along with its anti-cancer properties, melatonin has the potential to serve asan effective adjuvant in breast cancer therapy. It also inhibits the phosphorylation of mTOR and Akt, two essential pathways implicated in breast cancer growth, which may aid in overcoming resistance to targeted treatments like everolimus. The combination effects of melatonin and everolimus on hormone receptor-positive breast cancer remains unexplored. This study examined the effectiveness of melatonin when combined with everolimus for the treatment of hormone receptor-positive breast cancer.MethodsTo investigate the effects of melatonin and everolimus combination, we divided MCF-7 cells into four experimental groups: the control, Melatonin (3 mM), Everolimus (30 nM), and a combination of Melatonin and Everolimus (3 mM + 30 nM). Cell viability, apoptosis, autophagy activation, and mitochondrial function were evaluated using established techniques.ResultsBased on the cell viability test, the combination of 30 nM everolimus and 3 mM melatonin inhibited phosphorylation of 4E-BP1 and p70S6K, which are downstream effectors of the mTOR pathway, and reduced cell growth. In addition, co-administration of melatonin and everolimus increased apoptosis and led to Sub-G1 phase accumulation. LC3 protein expression and LC3 puncta analysis demonstrated autophagic activity. In terms of mitochondrial function, co-administration of melatonin with everolimus did not cause proton leakage or mitochondrial uncoupling, but did restore everolimus-induced respiratory inhibition.ConclusionsIn conclusion, melatonin is thought to improve the effectiveness of everolimus by inhibiting mTOR downstream effectors, enhancing apoptosis, activating autophagy, improving mitochondrial respiration, and reducing MCF-7 growth.Graphical

Unveiling the Bioactive Potential of Scabiosa rotata M. Bieb Fruits: A Landmark Study on Cytotoxic, Antioxidant, and Antibacterial Activities Through LC/MS–MS Profiling and Molecular Docking

Abstract The aim of this study was to investigate the antioxidant, cytotoxic, and antibacterial activities of ethanol extract (SRE) and its hexane (SRH), chloroform (SRC), ethyl acetate (SREA), and aqueous ethanol (SRAE) sub-extracts obtained from the fruits of Scabiosa rotata M. Bieb. Molecular docking studies were also performed to evaluate the interactions of the most active sub-extract with the human mitochondrial ABC transporter (ABCB10) protein, plays an important role in cellular oxidative stress regulation and mitochondrial function. Total phenolic (TPC) and flavonoid (TFC) contents and antioxidant radical scavenging activities (1, 1-diphenyl-2-picryl hydrazyl (DPPH) and 3-ethylbenzothiazoline-6 sulfonic acid (ABTS)) of all extracts were determined. Cytotoxic activity was evaluated on different cell lines like; HepG2 (liver cancer), MCF-7 (breast cancer), and HeLa (cervical cancer) cells. Antibacterial activity was tested against E. coli, P. aeruginosa, Enterococcus faecalis, and S. aureus. SREA showed the best antioxidant activity with IC50 values of 54.20 μg/mL and 48.56 μg/mL for DPPH and ABTS, respectively, and also had high TPC (499.06 mg GA/g) and TFC (327.45 mg QE/g). Furthermore, SREA showed significant cytotoxicity comparable to cisplatin with IC50 values of 51.29, 51.41, and 52.89 μg/mL for HepG2, MCF-7, and HeLa cells, respectively. However, none of the extracts showed antibacterial activity. The analysis using liquid chromatography-mass spectrometry (LC/MS–MS) on SREA found that the main phenolic compounds are chlorogenic acid, hesperidin, quinic acid, and isoorientin. Molecular docking of the major compounds showed that chlorogenic acid (2.21 mM) exhibited the strongest binding affinity, followed by hesperidin (5.83 mM), quinic acid (8.86 mM), and isoorientin (13 mM). These findings indicate the potential of SREA to be used as a natural antioxidant and anticancer agent.

Evaluating Bis-phenacyl bromide-based Bis-heterocyclic templates as anticancer prototypes and potential PARP1 inhibitors.

The newly synthesized bis-heterocyclic derivatives exhibited selective cytotoxicity towards MCF7 and PC-3 cells, while they were slightly cytotoxic or non-cytotoxic to the other examined cell lines. Derivatives 5a, 5b, 5c, 5d, 5e, 13, 18, 34, 35 and 36 (IC50<10 μM) were the most active derivatives against PC-3 cells. Derivatives 5a, 5d, 5e, 12, 25, 28a, and 34 with IC50 of 0.006‒0.417 μM revealed superior efficacy against MCF7 cells compared to doxorubicin. The derivatives' cytotoxicity against MCF7 cells might be attributed to their capacity to induce cell cycle cessation in the sub-G1 phase and trigger programmed cell death, as evidenced by the elevation of caspase-7, cytochrome C, BAX, and p53 proteins concentration, a decrease of BCL-2 protein level, and downregulation of cyclin-dependent kinases gene expression. All the synthesized derivatives demonstrated PARP1 inhibitory activity, with 5a, 5b, 5c, 5d, 5e, 8a, 13, 34, and 36 being the most potent derivatives, exhibiting PARP1 inhibitory activity superior to that of olaparib, with IC50 values at sub-nanomolar concentrations. Docking results revealed that the derivatives docked well with PARP1, supporting the results of the PARP1 activity assay. Our findings provide informative guidance for further optimization of these bis-heterocyclic derivatives as innovative anticancer agents and PARP1 inhibitors.

New Dimethoxyaryl-Sesquiterpene Derivatives with Cytotoxic Activity Against MCF-7 Breast Cancer Cells: From Synthesis to Topoisomerase I/II Inhibition and Cell Death Mechanism Studies

Breast cancer is a prevalent type of cancer worldwide, leading to both high incidence and mortality, and hence, effective and safe drugs are needed. Because of this, the use of natural products and their derivatives has become a popular strategy for developing new chemotherapeutic agents. In this study, 17 new sesquiterpene-aryl derivatives were synthesized using (−)-drimenol as the starting material. The cytotoxicity of these semi-synthetic derivatives was determined in MCF-7 cells, a breast cancer model, and in a non-tumor cell line, MCF-10, to evaluate selectivity. The results show that five of these sesquiterpene derivatives had IC50 values between 9.0 and 25 µM. Of these, compound 14c stands out for its higher cytotoxicity in MCF-7 cells but lower cytotoxicity in MCF-10 cells, being more selective than daunorubicin (selective index values of 44 and 28, respectively). In addition, compound 14c induced oxidative stress in MCF-7 cells, activated caspases-3/7, and selectively inhibited topoisomerase II (TOP2) versus topoisomerase I (TOP1) in MCF-7 cells. In silico studies allowed us to propose a binding mode for 14c to the TOP2 DNA complex to validate the experimental results. Therefore, this study demonstrated the importance of aryl-sesquiterpene structures and their promising profiles in the search for new bioinspired antitumor drugs in natural products.

In vitro antiproliferative activity, docking study, and plausible mode of action of (+)-2,2′-epicytoskyrin A against breast cancer MCF-7 and T47D cell lines

BackgroundThe endophytic fungus Diaporthe sp. GNBP-10 has been reported to produce metabolite bis-anthraquinone (+)-2,2′-epicytoskyrin A in high titers. In this study, we evaluated the potential of this metabolite as an anti-breast cancer agent by conducting antiproliferative activity studies against two breast cancer cell lines, MCF-7 and T47D.Materials and methodsThe antiproliferative activity of (+)-2,2′-epicytoskyrin A was determined by a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, fluorescence microscopy, and flow cytometry. In addition, the mode of action was assessed by several techniques, including the formation of apoptotic bodies using scanning electron microscopy (SEM) and the interaction or intercalation between (+)-2,2′-epicytoskyrin A with calf thymus DNA as indicated by the UV and 1H-NMR spectra. Moreover, molecular docking was also conducted.Results(+)-2,2′-Epicytoskyrin A exhibited significant antiproliferative effects against MCF-7 and T47D cells. The half-maximal inhibitory concentration (IC50) values for MCF-7 and T47D cells were 50.77 ± 33.23 µM and 36.24 ± 12.57 µM, respectively. (+)-2,2′-Epicytoskyrin A induced cancer cell death and promoted the formation of apoptotic bodies in both cell lines. These phenomena were expected to be facilitated by the DNA-binding ability of hydrogen atoms contained in (+)-2,2′-epicytoskyrin A. Molecular docking data indicated that (+)-2,2′-epicytoskyrin A might bind to the minor groove area of DNA, suggesting its potential as a DNA intercalator.ConclusionThis study highlighted the potential of (+)-2,2′-epicytoskyrin A as a promising candidate for future breast cancer treatment.Graphical abstract

Target screening and optimization of candidate compounds for breast cancer treatment using bioinformatics and computational chemistry approaches

ObjectivesThis study aimed to identify critical therapeutic targets and design potent antitumor compounds for breast cancer treatment through an integrated bioinformatics and computational chemistry approach.MethodsWe conducted initial screening and target intersection analysis to identify potential protein targets, highlighting the adenosine A1 receptor as a key candidate. Molecular docking and molecular dynamics (MD) simulations were performed to evaluate the binding stability between selected compounds and the human adenosine A1 receptor-Gi2 protein complex (PDB ID: 7LD3). A pharmacophore model was constructed based on binding information to guide the virtual screening of additional compounds with activity. Furthermore, we designed and synthesized a novel molecule based on this model, followed by in vitro biological evaluation using MCF-7 breast cancer cells.ResultsCompound 5 exhibited stable binding to the adenosine A1 receptor, as confirmed by docking and MD simulations. Pharmacophore-based screening identified compounds 6–9 with strong binding affinities. These findings guided Molecule 10, which was rationally designed and synthesized, showing potent antitumor activity against MCF-7 cells with an IC50 value of 0.032 µM, significantly outperforming the positive control 5-FU (IC50 = 0.45 µM).ConclusionThis study advances the understanding of molecular interactions in breast cancer therapy and demonstrates the potential of Molecule 10 as a highly effective therapeutic candidate. Integrating reverse drug screening, molecular modelling, and in vitro validation provides a robust platform for future drug discovery in breast cancer treatment.

Comprehensive Comparison Between STEM-HAADF and TEM Bright-field Mode for Imaging Resin Embedded Biological Samples.

Most investigations of resin embedded biological samples by transmission electron microscopy (TEM) have been performed in TEM bright-field mode where the electron beam transmits through the sample. Modern TEMs can also be used in scanning TEM mode (STEM) where the beam scans across the sample. The preferred detector for STEM mode is the high-angle annular dark-field (HAADF) detector. The aim of this study was to compare image quality of resin embedded biological samples such as yeast (Saccharomyces), algae (Chlorella, Haematococcus), plant leaves (Nicotiana), human cells (MCF7), and animal tissue (mouse liver and brain) between TEM bright-field and STEM-HAADF mode. Generally, images taken in STEM-HAADF mode showed better image quality in terms of contrast, brightness, and signal-to-noise ratio. Samples of sections that did not receive postcontrasting with uranyl acetate or lead citrate appeared significantly less grainy. Specifically, STEM-HAADF mode resulted in significantly better image quality of algae cells, MCF7, and liver cells that did not receive postcontrasting. Artifacts visible in TEM mode were absent in STEM-HAADF mode. Thus, we can conclude that STEM-HAADF mode has significant advantages when investigating resin embedded biological samples that have little contrast or sections that did not receive postcontrasting rendering postcontrasting of sections unnecessary.

In vitro antimicrobial and anticancer potentials of green synthesized luminescent carbon quantum dots derived from artichoke leaves

Naturally derived carbon quantum dots (CQDs) are novel carbon-based nanomaterials with excellent traits. It is highly demanded to develop CQDs from biowaste that have excellent photostability, a simple synthesis approach, and an appealing output so that they can be used widely in various fields. Herein, highly fluorescent CQDs were synthesized hydrothermally using artichoke leaves. The CQDs were synthesized and analyzed for their structure, optical properties, antimicrobial, and anticancer activities. The CQDs exhibited antimicrobial action against a single fungus strain in addition to Gram-positive and Gram-negative cells; also, the cytotoxicity against the MCF-7 cell line was evaluated as 96.5 µg/mL. The findings indicated that the spherical dots have a semi-spherical shape with the smallest size of 2.88 nm, and a zeta potential value of 37.31 V, thus confirming that the synthetic CQDs are in an outstanding colloidal state. When photoexcited at 320 nm, the dots were found to show blue fluorescence at 398 nm with a fluorescence quantum yield of 3.32%, long fluorescence decay time, high photostability, and good sensing for hydrogen peroxide. Additionally, the effect of ionic strength was evaluated.

Synthesis, Molecular Docking, and Biological Activity of New EGFR-Targeted Photosensitizers Based on Cationic Porphyrins Encapsulated into Pluronic F127 Micelles.

The development of new effective photosensitizers (PS) for photodynamic therapy (PDT) is one of the important tasks in medical and organic chemistry. PSs inhibiting epidermal growth factor receptors (EGFR) overexpressed in cancer cells are of particular importance. In this work, we proposed the design and molecular docking of novel hybrid photosensitizers based on meso-aryl-substituted porphyrins and the Erlotinib molecule, a clinically approved tyrosine kinase inhibitor. The spacer length between the macrocycles and Erlotinib, hydrophilicity, and hydrophobicity of the porphyrin ring substituents were varied in the obtained compounds to evaluate structure-activity relationships (SAR). Photophysical and photochemical characteristics were studied for all of the received compounds in the presence of solubilizers suitable for the creation of dosage forms. Nanomicelles based on Pluronic F127 were obtained and characterized for the received compounds. In vitro biological tests on three cancer cell lines, MCF-7 (breast carcinoma), A431 (epidermoid carcinoma), MDA-MB-231 (breast adenocarcinoma), and normal NKE cells (human kidney epithelial cells) were performed, which showed low dark toxicity as well as light-induced activity of conjugates in the nanomolar range. Confocal microscopy experiments showed preferred accumulation of UB-2 and a lower accumulation of UB-3 PSs. In the case of UB-3, we observed a pronounced colocalization with early endosome antigen (EEA1). Also, cell apoptosis and inhibition of phosphorylation of EGFR were demonstrated for the UB-3 compound. Thus, the proposed design of targeting PS containing cationic pyridyl moieties and a linker between the porphyrin macrocycle and Erlotinib can contribute to antitumor PDT.

QUERCETIN-LOADED GRAPHENE OXIDE NANOPARTICLES: SYNTHESIS, OPTIMIZATION, AND EVALUATION FOR BREAST CANCER TREATMENT

Objective: This study aimed to develop graphene oxide (GO) nanoparticles (NPs) loaded with Quercetin (QUE) for oncological applications, enhancing therapeutic efficacy while minimizing adverse effects. Methods: QUE-GO NPs were synthesized using Tween 80 and probe sonication, with optimization achieved through a Box-Behnken Design (BBD) that considered parameters including GO weight, surfactant volume, and sonication time. Results: The optimized batch 14 achieved an Entrapment Efficiency (EE) of 92.5±0.7%, with a particle size of 86.9±0.46 nm and a Polydispersity Index (PDI) of 0.158±0.001, indicating good stability. Drug release studies showed 88.60±2.3% release over 8 h (n = 3). Cytotoxicity assays in MCF-7 breast cancer and HEK293 noncancerous cells revealed enhanced cytotoxicity against MCF-7 cells (IC50: 126.20 µg/ml) (p&lt;0.001) compared to pure QUE's (MW: 302.24 g/mol) IC50 of 175.89 µg/ml (p&lt;0.05). The safety profile was observed for HEK 293 cells (IC50: 1009.40 µg/ml). Conclusion: These findings support QUE-GO NPs as a promising nanocarrier for targeted cancer therapy. A favourable safety profile was observed.

Uncovering the Mechanisms of Angelica glauca Edgew. In Breast Cancer: A Combined In Vitro and In Silico Approach.

Angelica glauca Edgew. is a medicinal herb native to the Himalayan region, renowned for its significant therapeutic potential and traditional use in treating various ailments. However, it has not been extensively investigated with pertinent scientific validation to establish its pharmacological relevance. This study aims to elucidate the anticancer potential of A. glauca essential oil on breast cancer by integrating in vitro and in silico approaches. The phytochemical profile of essential oil revealed the presence of important bioactive components including phthalide ((Z)-Ligustilide, 3-Butyl phthalide), monoterpene (alpha-terpineol, limonene), and sesquiterpene ((-)-Caryophyllene oxide, Kessane). The in vitro cytotoxicity using the MTT assay revealed the effectiveness of essential oil in reducing cancer cell viability and exhibited percent inhibition with IC₅₀ 91.77, 105.59, and 114.02µg/mL for root, seed, and leaf, respectively. In addition, mitochondrial membrane potential (MMP) assay demonstrated MMP disruption, and reactive oxygen species (ROS) assay showed increased ROS generation in the MCF-7 cells. In silico analysis identified three potential targets against breast cancer, that is, SRC, ESR1, and EGFR. Overall, our study highlighted the potential of A. glauca essential oil as a new therapeutic agent for breast cancer treatment and paves the way for further drug discovery.

SiRNA-guided dual-targeting nanocarrier for breast cancer treatment

Aims This study aimed to develop a thermoplastic polyurethane-oleic acid-based nanosystem (TPU-Ole NPs) incorporating siRNA and curcumin (CUR) to overcome multidrug resistance in breast cancer by silencing the c-myc gene. Methods TPU-Ole and CUR-loaded NPs were prepared via solvent evaporation and coated with poly-L-lysine (PLL) for siRNA attachment. NPs were characterised by dynamic light scattering (DLS) for mean diameter, polydispersity index (PDI), and zeta potential (ZP). Encapsulation (EE) and loading efficiencies (LE) were measured by NanoDrop. Release (pH 5.0; 7.4) and storage stability (pH 7.4) were evaluated using the eppendorf method. siRNA binding was confirmed by agarose gel electrophoresis. Gene silencing and apoptosis were assessed by RT-PCR and flow cytometry. Results Mean diameter, PDI, and ZP of NPs were 170 ± 2 nm, 0.011 ± 0.080, and −27.5 ± 0.11 mV. EE and LE were 75 ± 0.12 and 14.2 ± 0.06%. Sustained release and good stability were observed. Conclusion siRNA-CUR-NPs efficiently silenced c-myc and induced apoptosis in MCF-7 cells.

Differences in metabolite profiling by cold atmospheric plasma in normal and cancer cells.

Cold atmospheric plasma (CAP) recently it has been introduced as an innovative therapeutic approach for cancer cell treatment. However the cancer treatment faces questions about the selective anti-cancer capacity of CAP, the distinct molecular responses between cancer and normal cells. In present work 3T3 fibroblast and MCF-7 breast cancer epithelial cells were subjected to treatment of CAP with atmospheric discharge with runaway electrons. We have shown that a decrease in the 3T3 and MCF-7 cell viability under the influence of CAP. In addition, there was an increase in lactate dehydrogenase activity and an increase in the amount of NAD(P)H. An increase in the duration and dose of cold plasma exposure to living systems leaded to a change in the metabolic activity of cells. It was noted that after exposure to the culture of normal and cancer cells, there variability in biochemical and metabolic effects (lactate and growth of free form NAD(P)H), which was primarily accompanied shift in the equilibrium between oxidative phosphorylation and glycolysis. Therefore, cold plasma, at the same dose of radiation, has a stimulating effect on 3T3 cells and an apoptotic effect on MCF-7 cells, leading to a reduction in their metabolic activity. This results in a shift in the metabolic balance towards glycolysis for both 3T3 and MCF-7 cell cultures.

Biological Activities of Essential Oils and Hydrolates from Different Parts of Croatian Sea Fennel (Crithmum maritimum L.)

The traditional nutritional use of sea fennel (Crithmum maritimum L.) has been rediscovered and reestablished, making this halophyte plant a prominent ingredient in coastal cuisine and a subject of interest in various scientific disciplines, including pharmacy and medicine. The first objective of this study was to identify the volatile profiles of essential oils (EOs) and hydrolates derived from the leaves, flowers, and fruits of sea fennel using gas chromatography–mass spectrometry. A total of 25 different volatiles were identified in the EOs and 63 were identified in the hydrolates. Limonene was the most abundant component in the EOs (74.85%, 74.30%, and 67.41%, respectively), while in the hydrolates, it was terpinen-4-ol in the leaves (27.8%) and the flowers (36.7%) and (Z)-carveol in the fruits (11.4%). The second objective was to investigate the biological activities of the samples. The antioxidant and choline inhibitory activities of hydrolates were generally low, with the flower hydrolate providing the inhibition of both enzymes and the leaf hydrolate with the highest antiradical activity. The cytotoxic activities of the EOs and hydrolates were also investigated. The human breast adenocarcinoma cell line MDA-MB-23 was the most sensitive against EOs from the flowers and fruits, reaching the IC50 after 48 and 72 h, respectively. The leaf hydrolate exhibited cytotoxic activity after 72 h, while the flower hydrolate was effective after 48 h. The MCF-7 cell line was sensitive to the flower and fruit EOs, and the IC50 was reached at all the tested periods. Overall, the results highlight sea fennel as a rich source of bioactive compounds that have significant potential for greater utilization in the nutraceutical and pharmaceutical industries.

Evaluation of PAMAM Dendrimer-Stabilized Gold Nanoparticles: Two-Stage Procedure Synthesis and Toxicity Assessment in MCF-7 Breast Cancer Cells

Gold nanoparticles stabilized with polyamidoamine dendrimers are one of the potential candidates for use as a contrast agent in computed tomography and a drug delivery agent. This work demonstrates a rapid, two-step synthesis of such complexes, which are size-stable for up to 18 months. The first step of the synthesis involves a short sonication of gold (III) chloride hydrate with polyamidoamine dendrimers of the fourth generation, while the second step uses microwaves to reduce gold (III) chloride hydrate with sodium citrate. The developed synthesis method enables rapid production of spherical and monodisperse gold nanoparticles stabilized with polyamidoamine dendrimers. Physicochemical characterization of the gold nanoparticle-polyamidoamine dendrimers complexes was performed using ultraviolet-visible spectroscopy, dynamic light scattering technique, infrared spectroscopy, atomic force microscopy, and transmission electron microscopy. The toxicity of synthesized complexes on the breast cancer MCF-7 cell line has been studied using the tetrazolium salt reduction test. The produced gold nanoparticles revealed lower toxicity levels on the MCF-7 cell line after 18 months from synthesis compared with newly synthesized colloids. Synthesized gold nanoparticles stabilized with dendrimers and commercially available gold nanoparticles stabilized with sodium citrate show similar toxicity levels on breast cancer cells.

ROCK signaling is involved in the entosis of both nonepithelial and epithelial tumors, whereas N‑cadherin is involved in the entosis of nonepithelial tumors.

Entosis is a cell-in-cell phenomenon wherein cells detaching from the extracellular matrix are internalized by a neighboring cell. The present study examined whether entosis, which is observed in epithelial cells, also occurs in nonepithelial cells. The present study used the MCF-7 breast cancer cell line as a positive control for entosis and compared this with three representative sarcoma cell lines (RD, HT1080 and ICH-ERMS-1). The formation of cell-in-cell structures was induced by culturing cells in adherent and nonadherent conditions. Cell lines that formed the cell-in-cell structures were cultured in nonadherent conditions with and without Rho-associated coiled-coil containing protein kinase (ROCK) inhibition, and the cell-in-cell structures were evaluated in slides prepared from cell blocks. It was examined whether ROCK inhibition blocked the formation of cell-in-cell structures, and the expression levels of specific cadherins associated with entosis were determined using quantitative PCR. The proportion of cells with cell-in-cell structures was significantly higher in nonadherent conditions in both MCF-7 (P=0.0297) and RD (P=0.0098) cells, whereas few cell-in-cell structures were observed in both adherent and nonadherent conditions in HT1080 and ICH-ERMS-1 cells. Under nonadherent conditions, ROCK inhibition significantly reduced the proportion of cells with cell-in-cell structures in MCF-7 (P=0.0021) and RD (P=0.0407) cells. Based on quantitative PCR, among the five cadherin genes, the E-cadherin expression level was the lowest in MCF-7 cells (ΔCt, 2.6) and the N-cadherin expression level was lowest in RD cells (ΔCt, 4.8). By contrast, the N-cadherin expression levels were higher in HT1080 (ΔCt, 11.0) and ICH-ERMS-1 (ΔCt, 8.8) cells. These results suggested that the cell-in-cell phenomenon observed in RD cells is an entotic process based on its emergence in nonadherent culture conditions and the involvement of ROCK signaling. Entosis observed in RD cells was mediated via N-cadherin and not E-cadherin.

Rapid and sensitive detection of cell surface N-glycans in live cancer cells using a novel acid-activated concanavalin A nanosensor.

Rapid and sensitive detection of cell surface N-glycans in live cancer cells using a novel acid-activated concanavalin A nanosensor.

Bisphenol A enhanced cell migration through Kv3.4 in MCF7 cells.

Bisphenol A enhanced cell migration through Kv3.4 in MCF7 cells.