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Ecto‐5′‐nucleotidase (CD73) hydrolyses 5′AMP to adenosine and inorganic phosphate. Breast cancer cells (MDA‐MB‐231) express high CD73 levels, and this enzyme has been found to play a tumour‐promoting role in breast cancer. However, no studies have sought to investigate whether CD73 has differential affinity or substrate preferences between noncancerous and cancerous breast cells. In the present study, we aimed to biochemically characterise ecto‐5′‐nucleotidase in breast cancer cell lines and assess whether its catalytic function and tumour progression are correlated in breast cancer cells. The results showed that compared to nontumoral breast MCF‐10A cells, triple‐negative breast cancer MDA‐MB‐231 cells had a higher ecto‐5′‐nucleotidase expression level and enzymatic activity. Although ecto‐5′‐nucleotidase activity in the MDA‐MB‐231 cell line showed no selectivity among monophosphorylated substrates, 5′AMP was preferred by the MCF‐10A cell line. Compared to the MCF‐10A cell line, the MDA‐MB‐231 cell line has better hydrolytic ability, lower substrate affinity, and high inhibitory potential after treatment with a specific CD73 inhibitor α,β‑methylene ADP (APCP). Therefore, we demonstrated that a specific inhibitor of the ecto‐5‐nucleotidase significantly reduced the migratory and invasive capacity of MDA‐MB‐231 cells, suggesting that ecto‐5‐nucleotidase activity might play an important role in metastatic progression. [ABSTRACT FROM AUTHOR]

Collagen-based hydrogels are commonly used in mechanobiology to mimic the extracellular matrix. A quantitative analysis of the influence of collagen concentration and properties on the structure and mechanics of the hydrogels is essential for tailored design adjustments for specific in vitro conditions. We combined focused ion beam scanning electron microscopy and rheology to provide a detailed quantitative atlas of the mechanical and nanoscale three-dimensional structural alterations that occur when manipulating different hydrogel's physicochemistry. Moreover, we study the effects of such alterations on the phenotype of breast cancer cells and their mechanical interactions with the extracellular matrix. Regardless of the microenvironment's pore size, porosity or mechanical properties, cancer cells are able to reach a stable mesenchymal-like morphology. Additionally, employing 3D traction force microscopy, a positive correlation between cellular tractions and ECM mechanics is observed up to a critical threshold, beyond which tractions plateau. This suggests that cancer cells in a stable mesenchymal state calibrate their mechanical interactions with the ECM to keep their migration and invasiveness capacities unaltered. The paper presents a thorough study on the mechanical microenvironment in breast cancer cells during their interaction with collagen based hydrogels of different compositions. The hydrogels' microstructure were obtained using state-of-the-art 3D microscopy, namely focused ion beam-scanning electron microscope (FIB-SEM). FIB-SEM was originally applied in this work to reconstruct complex fibered collagen microstructures within the nanometer range, to obtain key microarchitectural parameters. The mechanical microenvironment of cells was recovered using Traction Force Microscopy (TFM). The obtained results suggest that cells calibrate tractions such that they depend on mechanical, microstructural and physicochemical characteristics of the hydrogels, hence revealing a steric hindrance. We hypothesize that cancer cells studied in this paper tune their mechanical state to keep their migration and invasiveness capacities unaltered. [Display omitted] [ABSTRACT FROM AUTHOR]

This study focused on preparing composite nanomats by incorporating silver nanoparticles (AgNPs) in polyvinylidene fluoride (PVDF) nanofibers through the electrospinning process. A short review of piezoelectric PVDF-related research is presented. PVDF is known for its biocompatibility and piezoelectric properties. Since electrical signals in biological tissues have been shown to be relevant for therapeutic applications, the influence of the addition of AgNPs to PVDF on its piezoelectricity is studied, due to the ability of AgNPs to increase the piezoelectric signal, along with providing antibacterial properties. The prepared samples were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Fourier transform infrared spectroscopy. In addition, the biological activity of composites was examined using a cytotoxicity assay and an assessment of the antibacterial activity. The obtained results show that the incorporation of AgNPs into PVDF nanofibers further enhances the piezoelectricity (crystalline β-phase fraction), already improved by the electrospinning process, compared to solution-casted samples, but only with a AgNPs/PVDF concentration of up to 0.3%; a further increase in the nanoparticles led to a β-phase reduction. The cytotoxicity assay showed a promising effect of PVDF/AgNPs nanofibers on the MDA-MB-231 breast cancer cell line, following the non-toxicity displayed in regard to the healthy MRC-5 cell line. The antibacterial effect of PVDF/AgNPs nanofibers showed promising antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus, as a result of the Ag content. The anticancer activity, combined with the electrical properties of nanofibers, presents new possibilities for smart, multifunctional materials for cancer treatment development. [ABSTRACT FROM AUTHOR]

Multidrug resistance is a serious problem in modern medicine and the reason for the failure of various therapies. A particularly important problem is the occurrence of multidrug resistance in cancer therapies which affects many cancer patients. Observations on the effect of metformin—a well-known hypoglycemic drug used in the treatment of type 2 diabetes—on cancer cells indicate the possibility of an interaction of this substance with drugs already used and, as a result, an increase in the sensitivity of cancer cells to cytostatics. The aim of this study was to evaluate the effect of metformin on the occurrence of multidrug resistance of breast cancer cells. The MCF-7-sensitive cell line and the MCF-7/DX cytostatic-resistant cell line were used for this study. WST-1 and LDH assays were used to evaluate the effects of metformin and doxorubicin on cell proliferation and viability. The effect of metformin on increasing the sensitivity of MCF-7 and MCF-7/DX cells to doxorubicin was evaluated in an MDR test. The participation of metformin in increasing the sensitivity of resistant cells to the effect of the cytostatic (doxorubicin) has been demonstrated. [ABSTRACT FROM AUTHOR]

Lippia alba (Mill.) N.E.Br. ex Britton and P. Wilson is used in folk medicine of Central and South America for its biological activities: i.e., antifungal, antibacterial, antiviral, and anti-inflammatory. Based on ethnopharmacological information and the increasing interest in this species, this work aimed to test a possible wide use of its essential oil (EO) in pharmaceutical and horticultural applications. Therefore, we focused the attention on the antioxidant activity of the oil as a possible tool to overcome the oxidative stress in both applications. For this purpose, we have chosen three aggressive breast cancer cell lines and two horticultural species (Solanum lycopersicum L. and Phaseolus acutifolius L.) that are very sensitive to salt stress. We determined the antioxidant activity of L. alba EO through the quantification of phenols and flavonoids. Regarding tomato and bean plants under salt stress, L. alba EO was used for the first time as a seed priming agent to enhance plant salt tolerance. In this case, the seed treatment enhanced the content of phenolic compounds, reduced power and scavenger activity, and decreased membrane lipid peroxidation, thus mitigating the oxidative stress induced by salt. While in breast cancer cells the EO treatment showed different responses according to the cell lines, i.e., in SUM149 and MDA-MB-231 the EO decreased proliferation and increased antioxidant activity and lipid peroxidation, showing high cytotoxic effects associated with the release of lactate dehydrogenase, vice versa no effect was observed in MDA-MB-468. Such antioxidant activity opens a new perspective about this essential oil as a possible tool to counteract proliferation in some cancer cell lines and in horticulture as a seed priming agent to protect from oxidative damage in crops sensitive to salinity. [ABSTRACT FROM AUTHOR]

The increasing incidence of breast cancer and bacterial biofilm in medical devices significantly heightens global mortality and morbidity, challenging synthetic drugs. Consequently, greener-synthesized nanomaterials have emerged as a versatile alternative for various biomedical applications, offering new therapeutic avenues. This study explores the synthesis of biocompatible zinc oxide (ZnONPs) nanoparticles using Gymnema sylvestre and its antibacterial, antibiofilm, and cytotoxic properties. Characterization of ZnONPs inferred that UV–Vis spectra exhibited a sharp peak at 370 nm. Fourier transform infrared spectroscopical analysis revealed the presence of active functional groups such as aldehyde, alkyne, cyclic alkene, sulfate, alkyl aryl ether, and Zn–O bonds. X-ray diffraction analysis results confirmed the crystalline nature of the nanoparticle. Scanning electron microscope analysis evidenced hexagonal morphology, and energy-dispersive X-ray analysis confirmed zinc content. High-resolution transmission electron microscope analysis showed hexagonal and rod-shaped ZnONPs with a size of 5 nm. Zeta potential results affirmed the stability of nanoparticles. The ZnONPs effectively inhibited gram-positive (18–20 mm) than gram-negative (12–18 mm) bacterial pathogens with lower bacteriostatic and higher bactericidal values. Biofilm inhibitory property inferred ZnONPs were more effective against gram-positive (38–94%) than gram-negative bacteria (27–86%). The concentration of ZnONPs to exert 50% biofilm-inhibitory is lower against gram-positive bacteria (179.26–203.95 μg/mL) than gram-negative bacteria (201.46–236.19 μg/mL). Microscopic visualization inferred that at 250 μg/mL, ZnONPs strongly disrupted biofilm formation, as evidenced by decreased biofilm density and altered architecture. The cytotoxicity of ZnONPs against breast cancer cells showed a dose-dependent reduction in cell viability with an IC50 value of 19.4 µg/mL. AO/EB staining indicated early and late apoptotic cell death of breast cancer cells under fluorescence microscopy. The results of hemolytic activity validated the biocompatibility of the ZnONPs. Thus, the unique properties of the green-synthesized ZnONPs suggest their potential as effective drug carriers for targeted delivery in cancer therapy and the treatment of biofilm-related infections. [ABSTRACT FROM AUTHOR]

The concept of drug repurposing is now widely utilized by biomedical scientists for drug discovery. An example of this is the use of selegiline (SEL), a monoamine oxidase inhibitor that was initially used for the management of depression but is now being considered for another purpose. This study compares the cytotoxic effects of SEL on different cancer cells. Further, the study explores the molecular mechanism of cell death, validating the possibility of its repurposing for cancer. Preliminary analysis of network pharmacological data was conducted in silico, followed by in vitro cytotoxicity tests on PC12, G361, MDA-MB231, MCF7, THP-1, and Hela cells under normoxic and hypoxic conditions, using the MTT assay. The mechanism of cell death was then confirmed by performing DAPI and FITC-conjugated Annexin V and Propidium Iodide (PI) staining assays. Additionally, ROS levels and PKC phosphorylation were also evaluated. In silico analysis has revealed that SEL is associated with ten genes linked to different cancer types. Specifically, SEL was most cytotoxic to neuronal pheochromocytoma, triple-negative human epithelial breast cancer cells, and ER+ and PR+ breast cancer cells. Furthermore, it was observed that this cell death occurred through ROS-independent apoptosis pathways. In addition, SEL was found to inhibit the phosphorylation of PKC, which may contribute to cell death. SEL induces apoptosis in breast cancer cells independently of reactive oxygen species and inhibits the phosphorylation of protein kinase C, which merits further exploration. [ABSTRACT FROM AUTHOR]

Melatonin (N‐acetyl‐5‐methoxytryptamine, MLT) is suggested as a preventive agent and potential therapeutic option for breast cancer via its antioxidant as well as anticancer effects by modulating estrogen dependent and independent pathways. However, its rapid metabolic inactivation led scientists to discover novel MLT analogues. Therefore, a series of new indole‐based hydrazide/hydrazone derivatives were synthesized and characterized as MLT analogues in the present study. The initial aim is to investigate the cytotoxicity of novel 1‐ethyl indole hydrazone derivatives against two human breast cancer cells (MCF‐7 and MDA‐MB‐231) as well as a non‐tumorigenic human breast epithelial cell (MCF‐10A). Selective cytotoxic compounds for cancer cells are further investigated for their effects on selected targets; agonist/antagonist activity on estrogen receptor (ER) and inhibitory effects on aromatase and CYP1B1. Their potential antioxidant activity was also investigated by both cell based and cell free in vitro assays. Possible binding of the compounds to the selected targets is also explored by molecular modelling studies. Nonsubstituted compound E1 inhibited human aromatase and the CYP1B1 enzyme with IC50 values of 0.89 μM and 0.5 μM, respectively. Compounds EI 4 and EI 11 exhibited ER antagonist activity with IC50 values of 2.88 μM and 5.29 μM, respectively. Additionally, both EI 4 and EI 11 inhibited CYP1B1 enzyme within 60–100 nanomolar range. In conclusion among 19 tested derivatives EI 1, EI 4 and EI 11 affected either one or more targets besides their selective cytotoxic effect for MCF‐7 cells suggesting that they can be promising candidates in prevention/treatment of ER‐positive breast cancer. Further studies are needed to elucidate their metabolism, in vivo effects, and safety. [ABSTRACT FROM AUTHOR]

The crystal structures of two newly synthesized nitrilotriacetate oxidovanadium(IV) salts, namely [QH][VO(nta)(H2O)](H2O)2 (I) and [(acr)H][VO(nta)(H2O)](H2O)2 (II), were determined. Additionally, the cytotoxic effects of four N-heterocyclic nitrilotriacetate oxidovanadium(IV) salts—1,10-phenanthrolinium, [(phen)H][VO(nta)(H2O)](H2O)0.5 (III), 2,2′-bipyridinium [(bpy)H][VO(nta)(H2O)](H2O) (IV), and two newly synthesized compounds (I) and (II)—were evaluated against prostate cancer (PC3) and breast cancer (MCF-7) cells. All the compounds exhibited strong cytotoxic effects on cancer cells and normal cells (HaCaT human keratinocytes). The structure–activity relationship analysis revealed that the number and arrangement of conjugated aromatic rings in the counterion had an impact on the antitumor effect. The compound (III), the 1,10-phenanthrolinium analogue, exhibited the greatest activity, whereas the acridinium salt (II), with a different arrangement of three conjugated aromatic rings, showed the lowest toxicity. The increased concentrations of the compounds resulted in alterations to the cell cycle distribution with different effects in MCF-7 and PC3 cells. In MCF-7 cells, compounds I and II were observed to block the G2/M phase, while compounds III and IV were found to arrest the cell cycle in the G0/G1 phase. In PC3 cells, all compounds increased the rates of cells in the G0/G1 phase. [ABSTRACT FROM AUTHOR]

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a crucial tumor suppressor protein with frequent mutations and alterations. Although protein therapeutics are already integral to numerous medical fields, their potential remains nascent. This study aimed to investigate the impact of stable, unphosphorylated recombinant human full-length PTEN and its truncated variants, regarding their tumor suppression activity with multiwalled-carbon nanotubes (MW-CNTs) as vehicles for their delivery in breast cancer cells (T-47D, ZR-75-1, and MCF-7). The cloning, overexpression, and purification of PTEN variants were achieved from E. coli, followed by successful binding to CNTs. Cell incubation with protein-functionalized CNTs revealed that the full-length PTEN-CNTs significantly inhibited cancer cell growth and stimulated apoptosis in ZR-75-1 and MCF-7 cells, while truncated PTEN fragments on CNTs had a lesser effect. The N-terminal fragment, despite possessing the active site, did not have the same effect as the full length PTEN, emphasizing the necessity of interaction with the C2 domain in the C-terminal tail. Our findings highlight the efficacy of full-length PTEN in inhibiting cancer growth and inducing apoptosis through the alteration of the expression levels of key apoptotic markers. In addition, the utilization of carbon nanotubes as a potent PTEN protein delivery system provides valuable insights for future applications in in vivo models and clinical studies. [ABSTRACT FROM AUTHOR]

Breast cancer is a leading cause of death in women worldwide. Cancer therapy based on stem cells is considered as a novel and promising platform. In the present study, we explore the therapeutic effects of human amniotic mesenchymal stromal cells (hAMSCs) through the reduction of focal adhesion kinase (FAK) activity, SHP-2, and cell adhesion proteins such as Paxillin, Vinculin, Fibronectin, Talin, and integrin αvβ3 expression in MDA-MB-231 breast cancer cells. For this purpose, we employed a co-culture system using 6-well plate transwell. After 72 h, hAMSCs-treated MDA-MB-231 breast cancer cells, the activity of focal adhesion kinase (FAK) and the expression of SHP-2 and cell adhesion proteins such as Paxillin, Vinculin, Fibronectin, Talin, and integrin αvβ3 expression were analyzed using western blot. The shape and migration of cells were also analyzed. Based on our results, a significant reduction in tumor cell motility through downregulation of the tyrosine phosphorylation level of FAK (at Y397 and Y576/577 sites) and cell adhesion expression in MDA-MB-231 breast cancer cells was demonstrated. Our findings indicate that hAMSCS secretome has therapeutic effects on cancer cell migration through downregulation of FAK activity and expression of cell adhesion proteins. [ABSTRACT FROM AUTHOR]

Magonia pubescens is a natural species from the Brazilian cerrado biome. Its fruits and seeds are used in the treatment of seborrheic dermatitis, a common inflammatory skin disease. In this work, the known compounds lapachol, stigmasterol, maniladiol and scopoletin were isolated from hexane and dichloromethane extracts of M. pubescens branches. The aqueous extract of this material was fractioned through a liquid-liquid partition and the obtained fractions were analyzed by UHPLC-MS/MS. The results obtained were compared with data from three databases, leading to the putative identification of 51 compounds from different classes, including flavonoids, saponins and triterpenes. The cytotoxicity of aqueous fractions was assayed against breast cancer (MDA-MB-231) and leukemia (THP-1 and K562) cells. The best activity was observed for fraction AE3 against MDA-MB-231 cells (IC50 30.72 µg.mL−1). [ABSTRACT FROM AUTHOR]

Leptin is an obesity-related hormone that plays an important role in breast cancer progression. Vasculogenic mimicry (VM) refers to the formation of vascular channels lined by tumor cells. This study aimed to investigate the relationship between leptin and VM in human breast cancer cells. VM was measured by a 3D culture assay. Signal transducers and activators of transcription 3 (STAT3) signaling, aquaporin-1 (AQP1), and the expression of VM-related proteins, including vascular endothelial cadherin (VE-cadherin), twist, matrix metalloproteinase-2 (MMP-2), and laminin subunit 5 gamma-2 (LAMC2), were examined by Western blot. AQP1 mRNA was analyzed by a reverse transcriptase-polymerase chain reaction (RT-PCR). Leptin increased VM and upregulated phospho-STAT3, VE-cadherin, twist, MMP-2, and LAMC2. These effects were inhibited by the leptin receptor-blocking peptide, Ob-R BP, and the STAT3 inhibitor, AG490. A positive correlation between leptin and AQP1 mRNA was observed and was confirmed by RT-PCR. Leptin upregulated AQP1 expression, which was blocked by Ob-R BP and AG490. AQP1 overexpression increased VM and the expression of VM-related proteins. AQP1 silencing inhibited leptin-induced VM and the expression of VM-related proteins. Thus, these results showed that leptin facilitates VM in breast cancer cells via the Ob-R/STAT3 pathway and that AQP1 is a key mediator in leptin-induced VM. [ABSTRACT FROM AUTHOR]

Novel Yttrium-metal-organic framework (Y-MOF) was synthesized under optimal conditions of microwave with a power of 20 W, the temperature of 30 degrees of centigrade, and time duration of 10 min. The products were characterized by SEM (morphology and size distribution), TGA (thermal stability), BET technique (surface area), and FTIR (characterization of the related group). The Yttrium-metal-organic framework (Y-MOF) synthesized in this study, after identifying and confirming the structure, was used as an efficient and recyclable catalyst in the synthesis of new pyrazolopyranopyrimidine derivatives. Following the study of the properties and applications of Y-MOF, its anticancer properties on breast cancer cells based on the MTT method were evaluated, and significant results were observed. In addition, the anticancer properties of the pyrazolopyranopyrimidine derivatives were investigated. [ABSTRACT FROM AUTHOR]

Background: Despite the fact that natives of Southeast Asia have been consuming Prismatomeris glabra for decades for a variety of health benefits, research on this species is not as extensive as that on other species due to its limited distribution. The purpose of this study was to determine the cytotoxicity and identify the bioactive compounds of P. glabra crude leaf extracts against the MCF-7 cell line. Results: We first examined the potential cytotoxic activity of P. glabra using the MTT assay against the MCF-7 cell line to determine the IC50 of the plant extracts at various concentrations at three time points (24 h, 48 h, and 72 h). Across all time points, the MTT assay revealed that the aqueous extract exhibited the lowest IC50 values (p < 0.05) compared to the ethanol and methanol extracts. All plant extracts exerted the ability to induce cell death in the MCF-7 cell line at all time points, and the optimal time for P. glabra to manifest its antiproliferative activities and promote cell death was 48 h. LC–MS analysis was conducted to reveal the components in plant extracts. Forty compounds were discovered in P. glabra's extracts, with the majority being flavonoids and triterpenoids. Five similar compounds were present in all three extracts. Further research should be conducted on these compounds to unveil a compound that fulfils the criteria as a promising anticancer agent. This research is of the utmost importance, as it provides a fundamental framework for the identification of alternative therapies for breast cancer and contributes implicitly to the development of new drugs. Conclusions: This study discovered that P. glabra crude leaf extracts have the potential to inhibit the MCF-7 cell line by inducing cell death. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) are gaining substantial importance in the fields of biotechnology and medicine. Its composites are metal oxides, silicates, polymers, graphene, fibers, dendrimers, etc. The greenly synthesized AgNPs possess advantages over conventional AgNPs in the form of fewer chemical reagents and a low temperature and pressure for synthesis. The anticancer efficacy of AgNPs is attributed to a number of variables, including size, shape, surface-to-volume ratio, etc. There are several ways to make SNPs, but the green synthesis of AgNPs, which uses harmless chemicals and natural reagents, has gained significant interest and value. In this review, a comprehensive range of topics related to silver nanoparticles, the environmentally friendly method of producing them from plants such as Aloe barbadensis miller (aloe vera), which have a vast medicinal uses, and their anticancer effectiveness against breast cancer cells are discussed. The synthesized AgNPs are characterized via a range of methods, for instance, Fourier Transform Infrared Spectroscopy (FTIR), UV–visible spectroscopy, Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), and X-ray Diffraction (XRD). This review study includes an investigation into the stability of produced nanoparticles, the wide range of nanoparticle forms, the many techniques used in the conglomeration of nanoparticles, and comparison methods emphasizing the benefits of green synthesis relative to traditional techniques. Furthermore, the discussion explores the chemical and structural makeup of nanoparticles.

Background: Our study aimed to assess the radiation sensitivity of BT20, a human breast tumor cell line, using the laser-trapping technique and compare it with N2a and 4T1 cells. Additionally, we investigated the impact of the antitumor compound 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) on radiation sensitivity. Methods and Materials: We employed laser trapping to calculate both the threshold ionization energy (TIE) and threshold radiation dose (TRD) for BT20, N2a, and 4T1 cells. We assessed the effect of DMDD on BT20 cells’ radiosensitivity and conducted comparisons across these cell lines. Results: Our findings reveal that DMDD significantly enhances the radiosensitivity of BT20 breast carcinoma cells. Moreover, we observed distinct trends in TIE and TRD across the three cell lines, with differences attributed to variations in cell size and composition. When multiple cell ionizations were considered, a notable reduction in TRD was observed, implicating factors such as the chain effect of ionizing radiation and the influence of DMDD. The study found that TIE increased with the number of cells in the trap while TRD consistently decreased across all three cell lines, suggesting comparable radiation sensitivity, and oligostilbene treatment further reduced TRD, presenting the potential for enhancing therapeutic ratios in cancer treatment. Conclusion: The antitumor compound DMDD enhances the radiosensitivity of BT20 breast carcinoma cells, highlighting its potential in cancer treatment. Furthermore, our study underscores the impact of cell size and multiple-cell ionizations on TRD. Leveraging laser trapping techniques, biocompatible nanoparticles, and advanced optical tweezers opens promising avenues for personalized and effective cancer therapy approaches.

ABSTRACTMed1 binds to a nuclear receptor and regulates transcription. Elevated Med1 protein expression promotes cancer growth in hormone-dependent breast and prostate cancers. Med1 protein expression was investigated by deubiquitinating enzymes (DUBs) overexpression in breast cancer cell lines. Various DNA constructs of SRT-DUBs were overexpressed in the MCF7 cell line, and Med1 protein expression was investigated by western blotting. The cell growth and in vitro invasion assay were performed in BRCA1-associated protein 1 (BAP1) wild type and mutant (C91A) overexpressed cells. Ubiquitination of the Med1 protein was observed, and Med1 protein expression and transcriptional activity were verified by various DUBs overexpressed. Although Med1 protein expression increased upon the overexpression of BAP1, it was not affected by the overexpression of BAP1 mutant (C91A). BAP1 was increased by the E2 treatment, which has an important effect on the breast cancer growth, and cell growth was decreased by BAP1 C91A overexpression. However, metastatic capacities were decreased by BAP1. In addition, the binding between the Med1 and the BAP1 protein was observed. These data suggested that BAP1 regulated Med1 protein expression in breast cancer cells and involved in cancer cell growth and metastasis by binding to Med1 protein.

Pharmacological properties of flavonoids have been reported, with an anticancer role amongst them, however, its mechanisms are not fully elucidated. In this study, the activity of quercetin and chrysin towards MCF-7 and MDA-MB-231 breast cancer cells was investigated. Cellular viability was determined after treatment with the compounds in different concentrations for 24 h. Secondly, cells were treated with fixed concentration of chrysin and different concentrations of quercetin with preincubation for 1 h. Both compounds inhibited cellular proliferation in dose-dependent manner. The association showed improvement in their cytotoxicity, more expressively with preincubation of quercetin. Quercetin and chrysin association induced cell cycle arrest in sub-G0/G1 phase in MDA-MB-231 cells, modified the expression of caspases-3 and ‐8,−8, inducing late apoptosis cell death. Taken together, our results demonstrate that both flavonoids inhibited cells growth in a dose-dependent manner and the association of quercetin improved chrysin’s toxic effect over the cell lines.

The aim of this work was to use and optimize a 1.5 Tesla magnetic resonance imaging (MRI) system for three-dimensional (3D) images of small samples obtained from breast cell cultures in vitro. The basis of this study was to design MRI equipment to enable imaging of MCF-7 breast cancer cell cultures (about 1 million cells) in 1.5 and 2 mL glass tubes and/or bioreactors with an external diameter of less than 20 mm. Additionally, the development of software to calculate longitudinal and transverse relaxation times is described. Imaging tests were performed using a clinical MRI scanner OPTIMA 360 manufactured by GEMS. Due to the size of the tested objects, it was necessary to design additional receiving circuits allowing for the study of MCF-7 cell cultures placed in glass bioreactors. The examined sample's volume did not exceed 2.0 mL nor did the number of cells exceed 1 million. This work also included a modification of the sequence to allow for the analysis of T1 and T2 relaxation times. The analysis was performed using the MATLAB package (produced by MathWorks). The created application is based on medical MR images saved in the DICOM3.0 standard which ensures that the data analyzed are reliable and unchangeable in an unintentional manner that could affect the measurement results. The possibility of using 1.5 T MRI systems for cell culture research providing quantitative information from in vitro studies was realized. The scanning resolution for FOV = 5 cm and the matrix was achieved at a level of resolution of less than 0.1 mm/pixel. Receiving elements were built allowing for the acquisition of data for MRI image reconstruction confirmed by images of a phantom with a known structure and geometry. Magnetic resonance sequences were modified for the saturation recovery (SR) method, the purpose of which was to determine relaxation times. An application in MATLAB was developed that allows for the analysis of T1 and T2 relaxation times. The relaxation times of cell cultures were determined over a 6-week period. In the first week, the T1 time value was 1100 ± 40 ms, which decreased to 673 ± 59 ms by the sixth week. For T2, the results were 171 ± 10 ms and 128 ± 12 ms, respectively. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is a prevalent malignancy among women worldwide. As an anticancer drug of pyrimidine nucleoside analogs, gemcitabine can be used to treat BC, but its clinical application is restricted due to drug resistance. This study investigated the effect of serum exosomal microRNA‐3662 (miR‐3662) on gemcitabine resistance in BC cells by targeting RNA‐Binding Motif Single‐Stranded Interacting Protein 3 (RBMS3) and related molecular mechanisms. We performed the bioinformatics analyses on the differential miRNAs in BC and predicted the downstream regulators. Quantitative real‐time polymerase chain reaction was conducted to determine miR‐3662 and RBMS3 expression, while dual luciferase was conducted to confirme the regulatory relationship between them. Flow cytometry, cell counting kit‐8, and transwell assays were applied to assess apoptosis, cell viability, invasion, and migration. The expression of marker proteins (TSG101, CD63, and CD81) in patients' serum exosomes was evaluated through western blot, and exosomes were observed using transmission electron microscopy. miR‐3662 expression was significantly upregulated in BC, and miR‐3662 knockdown significantly reduced BC cell viability and gemcitabine resistance. As the downstream gene of miR‐3662, RBMS3 was significantly downregulated in BC, and dual luciferase assay verified the binding of RBMS3‐3′UTR to miR‐3662. Rescue experiments revealed that silencing RBMS3 reversed the inhibitory effect of miR‐3662 knockdown on BC cells. Besides, we also found that miR‐3662 expression was significantly low in serum exosome samples from BC patients and could be transmitted to tumor cells. miR‐3662 was upregulated in serum exosomes and promoted BC cell progression and gemcitabine resistance by targeting RBMS3. [ABSTRACT FROM AUTHOR]

Chemotherapy is one of the most common strategies for cancer treatment, whereas drug resistance reduces the efficiency of chemotherapy and leads to treatment failure. The mechanism of emerging chemoresistance is complex and the effect of extracellular matrix (ECM) surrounding cells may contribute to drug resistance. Although it is well known that ECM plays an important role in orchestrating cell functions, it remains exclusive how ECM stiffness affects drug resistance. In this study, we prepared agarose hydrogels of different stiffnesses to investigate the effect of hydrogel stiffness on the chemoresistance of breast cancer cells to doxorubicin (DOX). Agarose hydrogels with a stiffness range of 1.5 kPa to 112.3 kPa were prepared and used to encapsulate breast cancer cells for a three-dimensional culture with different concentrations of DOX. The viability of the cells cultured in the hydrogels was dependent on both DOX concentration and hydrogel stiffness. Cell viability decreased with DOX concentration when the cells were cultured in the same stiffness hydrogels. When DOX concentration was the same, breast cancer cells showed higher viability in high-stiffness hydrogels than they did in low-stiffness hydrogels. Furthermore, the expression of P-glycoprotein mRNA in high-stiffness hydrogels was higher than that in low-stiffness hydrogels. The results suggested that hydrogel stiffness could affect the resistance of breast cancer cells to DOX by regulating the expression of chemoresistance-related genes. [ABSTRACT FROM AUTHOR]

Platinum-based drugs are widely recognized efficient anti-tumor agents, but faced with multiple undesirable effects. Here, four dinuclear platinum(II) complexes, [{Pt(1,2-pn)Cl}2(μ-pydz)]Cl2 (C1), [{Pt(ibn)Cl}2(μ-pydz)]Cl2 (C2), [{Pt(1,3-pn)Cl}2(μ-pydz)]Cl2 (C3) and [{Pt(1,3-pnd)Cl}2(μ-pydz)]Cl2 (C4), were designed (pydz is pyridazine, 1,2-pn is (±)-1,2-propylenediamine, ibn is 1,2-diamino-2-methylpropane, 1,3-pn is 1,3-propylenediamine, and 1,3-pnd is 1,3-pentanediamine). Interactions and binding ability of C1–C4 complexes with calf thymus DNA (CT-DNA) has been monitored by viscosity measurements, UV–Vis, fluorescence emission spectroscopy and molecular docking. Binding affinities of C1–C4 complexes to the bovine serum albumin (BSA) has been monitored by fluorescence emission spectroscopy. The tested complexes exhibit variable cytotoxicity toward different mouse and human tumor cell lines. C2 shows the most potent cytotoxicity, especially against mouse (4T1) and human (MDA-MD468) breast cancer cells in the dose- and time-dependent manner. C2 induces 4T1 and MDA-MD468 cells apoptosis, further documented by the accumulation of cells at sub-G1 phase of cell cycle and increase of executive caspase 3 and caspase 9 levels in 4T1 cells. C2 exhibits anti-proliferative effect through the reduction of cyclin D3 and cyclin E expression and elevation of inhibitor p27 level. Also, C2 downregulates c-Myc and phosphorylated AKT, oncogenes involved in the control of tumor cell proliferation and death. In order to measure the amount of platinum(II) complexes taken up by the cells, the cellular platinum content were quantified. However, C2 failed to inhibit mouse breast cancer growth in vivo. Chemical modifications of tested platinum(II) complexes might be a valuable approach for the improvement of their anti-tumor activity, especially effects in vivo. Dinuclear platinum(II) complex [{Pt(ibn)Cl}2(μ-pydz)]Cl2 shows anti-tumor activity, triggers the apoptosis and reduces the proliferation of mouse breast cancer cells in vitro. However, its inhibitory effect on tumor growth in vivo is absent. [ABSTRACT FROM AUTHOR]

Simple Summary: RNA-binding proteins (RBPs) play a critical role in controlling gene expression post-transcriptionally and their dysregulation can lead to various diseases, including cancer. One such RBP is HuR, whose levels have been associated with a poor clinical prognosis in breast cancer. Nevertheless, the precise molecular mechanism underlying this connection remains incompletely characterized. Our study uncovers that HuR targets SOX9 mRNA in breast cancer cells and provides compelling evidence supporting HuR's involvement in cell migration and invasion. RNA-binding proteins play diverse roles in cancer, influencing various facets of the disease, including proliferation, apoptosis, angiogenesis, senescence, invasion, epithelial–mesenchymal transition (EMT), and metastasis. HuR, a known RBP, is recognized for stabilizing mRNAs containing AU-rich elements (AREs), although its complete repertoire of mRNA targets remains undefined. Through a bioinformatics analysis of the gene expression profile of the Hs578T basal-like triple-negative breast cancer cell line with silenced HuR, we have identified SOX9 as a potential HuR-regulated target. SOX9 is a transcription factor involved in promoting EMT, metastasis, survival, and the maintenance of cancer stem cells (CSCs) in triple-negative breast cancer. Ribonucleoprotein immunoprecipitation assays confirm a direct interaction between HuR and SOX9 mRNA. The half-life of SOX9 mRNA and the levels of SOX9 protein decreased in cells lacking HuR. Cells silenced for HuR exhibit reduced migration and invasion compared to control cells, a phenotype similar to that described for SOX9-silenced cells. [ABSTRACT FROM AUTHOR]

Anthocyanin oligomers (AOs) are phytochemicals synthesized by fermenting anthocyanins extracted from grape skins and are more biologically active than monomeric anthocyanins. In this study, we evaluate the effects of an AO on triple-negative MDA-MB-231 and HER2-overexpressing SK-BR-3 breast cancer cells. The cell viability of MDA-MB-231 and SK-BR-3 cells was significantly inhibited in a concentration-dependent manner by AO treatment for 24 h, while delphinidin (a monomeric anthocyanin) had no effect on cell viability. In addition, the AO increased H2A.X phosphorylation (a marker of DNA damage), reduced RAD51 (a DNA repair protein) and survivin (a cell survival factor) protein levels, and induced apoptosis by caspase-3-dependent PARP1 cleavage in both cell lines. Surprisingly, the AO induced autophagy by increasing intracellular LC3-II puncta and LC3-II and p62 protein levels. In addition, the AO inhibited the mTOR pathway in MDA-MB-231 and SK-BR-3 cells by suppressing the HER2, EGFR1, and AKT pathways. These results demonstrate that the anti-cancer effect of the AO was due to the induction of apoptosis and autophagy via cleaved caspase-3-mediated PARP1 cleavage and mTOR pathway inhibition, respectively. Furthermore, our results suggest that anthocyanin oligomers could be considered potential candidates for breast cancer treatment. [ABSTRACT FROM AUTHOR]

In hormone-responsive breast cancer cells, progesterone (P4) has been shown to act via its nuclear receptor (nPR), a ligand-activated transcription factor. A small fraction of progesterone receptor is palmitoylated and anchored to the cell membrane (mbPR) forming a complex with estrogen receptor alpha (ERα). Upon hormone exposure, either directly or via interaction with ERα, mbPR activates the SRC/RAS/ERK kinase pathway leading to phosphorylation of nPR by ERK. Kinase activation is essential for P4 gene regulation, as the ERK and MSK1 kinases are recruited by the nPR to its genomic binding sites and trigger chromatin remodeling. An interesting open question is whether activation of mbPR can result in gene regulation in the absence of ligand binding to intracellular progesterone receptor (iPR). This matter has been investigated in the past using P4 attached to serum albumin, but the attachment is leaky and albumin can be endocytosed and degraded, liberating P4. Here, we propose a more stringent approach to address this issue by ensuring attachment of P4 to the cell membrane via covalent binding to a stable phospholipid. This strategy identifies the actions of P4 independent from hormone binding to iPR. We found that a membrane-attached progestin can activate mbPR, the ERK signaling pathway leading to iPR phosphorylation, initial gene regulation and entry into the cell cycle, in the absence of detectable intracellular progestin. [ABSTRACT FROM AUTHOR]

This article, published in Frontiers in Pharmacology, explores the discovery and potential therapeutic uses of a peptide called ERα17p, which is the first peptidic modulator of the estrogen receptor GPER. The peptide has demonstrated anti-proliferative, anti-nociceptive, and anti-inflammatory effects, and has shown promise in breast cancer cells and animal models. The article suggests that further research on ERα17p could lead to new treatments for various diseases. Additionally, the text discusses the importance of incorporating recent findings into the study of GPER modulators, including substances like aldosterone and the amyloid β1-42 peptide, which may play a role in membrane-initiated signaling. The article includes information about author contributions, funding, conflict of interest, and a disclaimer that the claims expressed in the article are solely those of the authors. [Extracted from the article]

Ziziphus Spina-Christi (L.) (ZSC) is a traditional Arabian medicinal plant used to treat inflammatory symptoms, swellings and pain since long. Triple negative breast cancer (TNBC) is a form of cancer with a poor prognosis owing to the paucity of therapy alternatives. Two of the most critical pathways of TNBC development are Wnt/β-catenin signaling and autophagy. In the present study, we intended to identify the possible mechanisms of the cytotoxic effects mediated by ZSC extract on MDA-MB-231 breast cancer cells and to improve the efficacy of DOX in combination with ZSC. The MTT test was used to estimate cell viability and IC50 values. Apoptosis was detected using AnnexinV-FITC detection kit. ELISA was used to measure caspase-3 levels. Cell cycle and the level of autophagosome marker LC3-II were analysed using flow cytometry. Acidic vesicular organelle (AVOs) formation was observed by fluorescence microscopy. Real-time PCR was used to monitor changes in gene expression of β-catenin and autophagic adapter NBR1. It was shown that ZSC treatment dose-dependently inhibited MDA-MB-231 cell viability and induced apoptosis with accompanying elevation of caspase-3 level. Besides ZSC caused a significant elevation in LC3II level and downregulation of NBR1 gene expression with subsequent downregulation of β-catenin gene expression, indicating the inhibition of the oncogenic Wnt pathway. ZSC and DOX combination had synergistic cytotoxic effect by more effective suppression of Wnt pathway and induction of apoptosis and autosis.

The toxicity of drugs for chemotherapy and cell resistance to their action are the main obstacles in anticancer therapy. Advances in nanotechnology may offer an alternative to traditional methods of anticancer therapy and overcoming drug resistance. The study was carried out on doxorubicin-resistant MCF-7/Dox breast cancer cells and BALB/3T3 clone A31 as a model of normal fibroblasts with the use of Dextran-graft-polyacrylamide/zinc oxide (D-PAA/ZnO) nanoparticles. Cytomorphological analysis was carried out after cells staining with acridine orange. Immunocytochemical study of Ki-67, p53, Bcl-2, Bax, E-cadherin, N-cadherin, СD44 expression was done. Cytotoxicity of D-PAA/ZnO nanoparticles (EC50 = 2.2 mM) against MCF-7/Dox cancer cells but not against normal fibroblasts was demonstrated. The increased expression of proapoptotic proteins, E-cadherin, CD44 and decreased expression of proliferation-associated marker Ki-67 in cancer cells treated with D-PAA/ZnO was revealed. Cytotoxicity of D-PAA/ZnO NPs against MCF-7/Dox cancer cells can be potentially used for elaboration of new approaches to cancer treatment.

Abstract Background Gremlin-1 (GREM1) and Gremlin-2 (GREM2) are bone morphogenetic protein antagonists that play important roles in organogenesis, tissue differentiation, and tissue homeostasis. Although GREM1 has been reported to be involved in promoting various cancers, little has been reported about effects of GREM2 on cancer. Recently, it has been reported that GREM2 can inhibit adipogenesis in adipose-derived stromal/stem cells. However, as an inhibitor of adipogenesis, the role of GREM2 in cancer progression is not well understood yet. Methods Pre-adipocyte 3T3-L1 cells overexpressing mock or Grem2 were established using a lentiviral transduction system and differentiated into adipocytes-mock and adipocytes-Grem2, respectively. To investigate the effect of adipocyte-Grem2 on breast cancer cells, we analyzed the proliferative and invasion abilities of spheroids using a 3D co-culture system of breast cancer cells and adipocytes or conditioned medium (CM) of adipocytes. An orthotopic breast cancer mouse model was used to examine the role of adipocytes-Grem2 in breast cancer progression. Results Grem2 overexpression suppressed adipogenesis of 3T3-L1 cells. Proliferative and invasion abilities of spheroids formed by co-culturing MTV/TM-011 breast cancer cells and adipocytes-Grem2 were significantly reduced compared to those of spheroids formed by co-culturing MTV/TM-011 cells and adipocytes-mock. Compared to adipocytes-mock, adipocytes-Grem2 showed decreased mRNA expression of several adipokines, notably IL-6. The concentration of IL-6 in the CM of these cells was also decreased. Proliferative and invasive abilities of breast cancer cells reduced by adipocytes-Grem2 were restored by IL-6 treatment. Expression levels of vimentin, slug, and twist1 in breast cancer cells were decreased by treatment with CM of adipocytes-Grem2 but increased by IL-6 treatment. In orthotopic breast cancer mouse model, mice injected with both MTV/TM-011 cells and adipocytes-Grem2 showed smaller primary tumors and lower lung metastasis than controls. However, IL-6 administration increased both the size of primary tumor and the number of metastatic lung lesions, which were reduced by adipocytes-Grem2. Conclusions Our study suggests that GREM2 overexpression in adipocytes can inhibit adipogenesis, reduce the expression and secretion of several adipokines, including IL-6, and ultimately inhibit breast cancer progression.

Lippia alba (Mill.) N.E.Br. ex Britton and P. Wilson is used in folk medicine of Central and South America for its biological activities: i.e., antifungal, antibacterial, antiviral, and anti-inflammatory. Based on ethnopharmacological information and the increasing interest in this species, this work aimed to test a possible wide use of its essential oil (EO) in pharmaceutical and horticultural applications. Therefore, we focused the attention on the antioxidant activity of the oil as a possible tool to overcome the oxidative stress in both applications. For this purpose, we have chosen three aggressive breast cancer cell lines and two horticultural species (Solanum lycopersicum L. and Phaseolus acutifolius L.) that are very sensitive to salt stress. We determined the antioxidant activity of L. alba EO through the quantification of phenols and flavonoids. Regarding tomato and bean plants under salt stress, L. alba EO was used for the first time as a seed priming agent to enhance plant salt tolerance. In this case, the seed treatment enhanced the content of phenolic compounds, reduced power and scavenger activity, and decreased membrane lipid peroxidation, thus mitigating the oxidative stress induced by salt. While in breast cancer cells the EO treatment showed different responses according to the cell lines, i.e., in SUM149 and MDA-MB-231 the EO decreased proliferation and increased antioxidant activity and lipid peroxidation, showing high cytotoxic effects associated with the release of lactate dehydrogenase, vice versa no effect was observed in MDA-MB-468. Such antioxidant activity opens a new perspective about this essential oil as a possible tool to counteract proliferation in some cancer cell lines and in horticulture as a seed priming agent to protect from oxidative damage in crops sensitive to salinity.

Multidrug resistance is a serious problem in modern medicine and the reason for the failure of various therapies. A particularly important problem is the occurrence of multidrug resistance in cancer therapies which affects many cancer patients. Observations on the effect of metformin—a well-known hypoglycemic drug used in the treatment of type 2 diabetes—on cancer cells indicate the possibility of an interaction of this substance with drugs already used and, as a result, an increase in the sensitivity of cancer cells to cytostatics. The aim of this study was to evaluate the effect of metformin on the occurrence of multidrug resistance of breast cancer cells. The MCF-7-sensitive cell line and the MCF-7/DX cytostatic-resistant cell line were used for this study. WST-1 and LDH assays were used to evaluate the effects of metformin and doxorubicin on cell proliferation and viability. The effect of metformin on increasing the sensitivity of MCF-7 and MCF-7/DX cells to doxorubicin was evaluated in an MDR test. The participation of metformin in increasing the sensitivity of resistant cells to the effect of the cytostatic (doxorubicin) has been demonstrated.

Protein–drug interactions are crucial for understanding drug delivery and cell functions. Jacalin is a suitable molecule for such targeting, as it specifically recognizes the tumor-associated Thomsen–Friedenreich (TF) antigen that is expressed on the glycosylated proteins in cancer cells. The present paper describes the interaction of curcumin and jacalin, a possible carrier molecule for the delivery of antitumor drugs due to its ability to recognize tumor cells. Our results have shown that both steady-state fluorescence and fluorescent labelling of jacalin are two reliable methods to determine jacalin-curcumin interactions. The affinity of jacalin for curcumin is consistently within the micromolar range (using fluorescence and microscale thermophoresis) showing high-affinity binding of the complex. In vitro experiments on triple-negative breast cancer MDA-MB-231 cells indicated inhibition of cell growth after treating with the jacalin-curcumin complex for 48 h. The cell survival fraction was significantly reduced to 50% after combined treatment. In this paper, we report for the first time about the jacalin-curcumin interaction. We quantified this unique biomolecular interaction and gathered additional information on the binding event. We observed that the jacalin-curcumin complex inhibits the proliferation of the triple-negative breast cancer MDA-MB-231 cells. [ABSTRACT FROM AUTHOR]

The history of the use of natural compounds as therapeutic agents goes back many centuries. Being the first objects of interest in the early days of medicine, natural compounds are still of great relevance, considering the improvement of methods for isolation, chemical transformation, and synthesis. They are also used in oncology, with the advantage of preventing the development of toxicity to normal cells and resistance in tumor cells. One of the promising classes of natural compounds with antitumor activity is lignans. We studied a number of lignans (arctiin, honokiol, matairesinol, pinoresinol, myrislignan, enterodiol, and enterolactone) in the breast cancer cell line MCF7 and the subline MCF7/FUL with acquired resistance to the antiestrogen fulvestrant. Antiproliferative activity was assessed using the MTT test. An analysis of the level of intracellular proteins was carried out via immunoblotting. Based on the results of the screening, the most active compound was honokiol; it had the lowest IC50 value for both MCF7 and MCF7/FUL cells, 19.7 μM and 9.1 μM, respectively. The revealed antiproliferative activity of honokiol against resistant cells prompted us to study its effects on intracellular proteins associated with proliferation and cell death. Honokiol suppressed the expression of Bcl-2 (an inhibitor of apoptosis) and cyclin D1 (a cell cycle regulator) in both cell lines, but this effect was more pronounced in the resistant subline. The decrease in the expression of antiapoptotic and proliferative proteins induced by honokiol is consistent with its antiproliferative effect, which is more pronounced in resistant subline MCF7/FUL. [ABSTRACT FROM AUTHOR]

Potassium Calcium-Activated Channel Subfamily N1 (KCNN1), an integral membrane protein, is thought to regulate neuronal excitability by contributing to the slow component of synaptic after hyperpolarization. However, the role of KCNN1 in tumorigenesis has been rarely reported, and the underlying molecular mechanism remains unclear. Here, we report that KCNN1 functions as an oncogene in promoting breast cancer cell proliferation and metastasis. KCNN1 was overexpressed in breast cancer tissues and cells. The pro-proliferative and pro-metastatic effects of KCNN1 were demonstrated by CCK8, clone formation, Edu assay, wound healing assay and transwell experiments. Transcriptomic analysis using KCNN1 overexpressing cells revealed that KCNN1 could regulate key signaling pathways affecting the survival of breast cancer cells. KCNN1 interacts with ERLIN2 and enhances the effect of ERLIN2 on Cyclin B1 stability. Overexpression of KCNN1 promoted the protein expression of Cyclin B1, enhanced its stability and promoted its K63 dependent ubiquitination, while knockdown of KCNN1 had the opposite effects on Cyclin B1. Knockdown (or overexpression) ERLNI2 partially restored Cyclin B1 stability and K63 dependent ubiquitination induced by overexpression (or knockdown) of KCNN1. Knockdown (or overexpression) ERLIN2 also partially neutralizes the effects of overexpression (or knockdown) KCNN1-induced breast cancer cell proliferation, migration and invasion. In paired breast cancer clinical samples, we found a positive expression correlations between KCNN1 and ERLIN2, KCNN1 and Cyclin B1, as well as ERLIN2 and Cyclin B1. In conclusion, this study reveals, for the first time, the role of KCNN1 in tumorigenesis and emphasizes the importance of KCNN1/ERLIN2/Cyclin B1 axis in the development and metastasis of breast cancer. [ABSTRACT FROM AUTHOR]

The wave propagation characteristics of biological tissues are of high importance in improving healthcare technologies and can be used as an early clinical indicator of many diseases. However, the current mathematical models that describe the mechanical properties of biological tissues do not account for the difference in softening and hardening observed at different scales and this limits their utility in biomedical imaging. In this paper, a higher-order nonlocal model is developed to study in-plane wave propagation in healthy, benign, and cancerous breast tissues. To verify the mathematical approach, finite element simulations are conducted. Furthermore, a sequential deep neural network model of feedforward type with multiple hidden layers is developed to understand the intrinsic in-plane wave characteristics of breast tissues. The deep learning algorithm shows potential in accurately extracting the frequencies and phase velocities of breast lesions under in-plane waves even when there is a limited number of clinical samples. Using the higher-order nonlocal model, significant differences between healthy fibroglandular tissue and early breast cancer in the form of ductal carcinoma in situ have been found. The combination of nonlocal and strain gradient parameters allows for the concurrent incorporation of stiffness hardening and softening, solving the rigid-tumour–soft-cell paradox of cancer biomechanics. [ABSTRACT FROM AUTHOR]

Researchers have become increasingly interested in nanoparticles made from plants because of their stability and large surface area. In the current study, iron oxide and iron dioxide nanoparticles were synthesized using aerial parts of the E. tirucalli as a reducing agent. The nanoparticles were analyzed using various techniques, including Ultraviolet-visible spectroscopy, Fourier Transform Infrared spectroscopy, X-ray diffractometer, X-ray photoelectron spectroscopy, X-ray energy dispersive spectroscopy, Scanning electron Microscopy, and Transmission Electron Microscopy. The nanoparticles were then investigated for their antiproliferative effect against MCF-7, SK-BR-3, MDA-MB231, and Vero cell lines. The results confirmed the formation of FeO and FeO2 nanoparticles by color change and a UV absorbance peak between 220–390 nm. EDS analysis showed traces of Fe and O, while TEM confirmed the nanoparticle size of 100 nm. FTIR showed a peak at 514 nm. The FeO-RT NPs demonstrated over 80% antiproliferative activity against the MCF-7 cell line at a concentration of 10 μg/mL. while doxorubicin, FeO-RT NPs, and DCM extract showed similar activity against the MDA-MB231 cell line at 10 and 1 g/mL concentrations. However, Vero and SK-BR-3 cell lines showed decreased antiproliferative activity. This study highlights the environmentally friendly use and safe application of iron oxide NPs in cancer therapy. [ABSTRACT FROM AUTHOR]

Obesity-associated perturbations in the normal secretion of adipocytokines from white adipocytes can drive the metastatic progression of cancer. However, the association between obesity-induced changes in secretory factors of white adipocytes and subsequent transactivation of the downstream effector proteins impacting metastasis in breast cancer cells remains unclear. Focal adhesion kinase, a cytoplasmic signal transducer, regulates the biological phenomenon of metastasis by activating downstream targets such as beta-catenin and MMP9. Thus, the possible role of phosphorylated FAK in potentiating cancer cell migration was investigated. To elucidate this potential relationship, MCF7 (ER+), MDA-MB-231 (Triple Negative) breast cancer cells, and MCF-10A non-tumorigenic breast cells were exposed to in vitro murine adipocyte-conditioned medium derived from 3T3-L1 MBX cells differentiated to obesity with fatty acid supplementation. Our results show that the conditioned medium derived from these obese adipocytes enhanced motility and invasiveness of breast cancer cells. Importantly, no such changes were observed in the non-tumorigenic breast cells. Our results also show that increased FAK autophosphorylation was followed by increased expression of beta-catenin and MMP9 in the breast cancer cells when exposed to obese adipocyte-conditioned medium, but not in the MCF10A cells. These results indicate that adipocyte-derived secretory factors induced FAK activation through phosphorylation. This in turn increased breast cancer cell migration and invasion by activating its downstream effector proteins beta-catenin and MMP9. [ABSTRACT FROM AUTHOR]

Nanoparticles' size-dependent features make them exceptional and necessary in a wide range of human activities. We examined the toxicity and apoptotic activities of Cu/Fe nanocomposite (green Cu/Fe nanoparticles [g-Cu-FeNPs]) on human liver (HuH-7) and breast cancer (MCF-7) cells for 24 h. Prior to the treatment of g-Cu-FeNPs, the size of the nanoparticles (NPs) was determined by scanning electron microscope (SEM) and transmission electron microscope (TEM). The shape of g-Cu-FeNPs was polygonal, with a size of 24 ±2 nm. The cytotoxicity of g-Cu-FeNPs on both cells was determined by using MTTand NRU assays, and the cytotoxicity of NPs was increased in a concentration-dependent manner. On the basis of the MTT result, the median inhibitory concentration (IC50) at 24 h was determined to be 324 and 368 µg/mL for HuH-7 and MCF-7 cells, respectively. The generation of intracellular reactive oxygen species, lipid peroxidation, and catalase levels in HuH-7 cells was higher than in MCF-7 cells at 216 µg/mL of g-Cu-FeNPs. The cell death mechanism was assessed using Hoechst 33342 and propidium iodide staining. Maximum apoptotic and necrotic cells were observed at a higher concentration of NPs in HuH-7 cells than in MCF-7 calls. This study warrants the application of g-Cu-FeNPs in daily life and provides vital information about the toxicity of g-Cu-FeNPs. [ABSTRACT FROM AUTHOR]

Background: Gremlin-1 (GREM1) and Gremlin-2 (GREM2) are bone morphogenetic protein antagonists that play important roles in organogenesis, tissue differentiation, and tissue homeostasis. Although GREM1 has been reported to be involved in promoting various cancers, little has been reported about effects of GREM2 on cancer. Recently, it has been reported that GREM2 can inhibit adipogenesis in adipose-derived stromal/stem cells. However, as an inhibitor of adipogenesis, the role of GREM2 in cancer progression is not well understood yet. Methods: Pre-adipocyte 3T3-L1 cells overexpressing mock or Grem2 were established using a lentiviral transduction system and differentiated into adipocytes-mock and adipocytes-Grem2, respectively. To investigate the effect of adipocyte-Grem2 on breast cancer cells, we analyzed the proliferative and invasion abilities of spheroids using a 3D co-culture system of breast cancer cells and adipocytes or conditioned medium (CM) of adipocytes. An orthotopic breast cancer mouse model was used to examine the role of adipocytes-Grem2 in breast cancer progression. Results: Grem2 overexpression suppressed adipogenesis of 3T3-L1 cells. Proliferative and invasion abilities of spheroids formed by co-culturing MTV/TM-011 breast cancer cells and adipocytes-Grem2 were significantly reduced compared to those of spheroids formed by co-culturing MTV/TM-011 cells and adipocytes-mock. Compared to adipocytes-mock, adipocytes-Grem2 showed decreased mRNA expression of several adipokines, notably IL-6. The concentration of IL-6 in the CM of these cells was also decreased. Proliferative and invasive abilities of breast cancer cells reduced by adipocytes-Grem2 were restored by IL-6 treatment. Expression levels of vimentin, slug, and twist1 in breast cancer cells were decreased by treatment with CM of adipocytes-Grem2 but increased by IL-6 treatment. In orthotopic breast cancer mouse model, mice injected with both MTV/TM-011 cells and adipocytes-Grem2 showed smaller primary tumors and lower lung metastasis than controls. However, IL-6 administration increased both the size of primary tumor and the number of metastatic lung lesions, which were reduced by adipocytes-Grem2. Conclusions: Our study suggests that GREM2 overexpression in adipocytes can inhibit adipogenesis, reduce the expression and secretion of several adipokines, including IL-6, and ultimately inhibit breast cancer progression. [ABSTRACT FROM AUTHOR]

Background: We investigated the anti-cancer effect of carnosine-loaded niosomes (Car-NIO) and melittin-loaded niosomes (Mel-NIO) with olaparib in breast cancer cell lines (MCF-7 and MDA-MB-231). Methods: The thin film method was used for preparing the niosomes and characterized in terms of morphology, size, and polydispersity index (PDI). We further evaluated the impact of these peptides on breast cancer cells viability, RTqPCR assays, malondialdehyde (MDA) activity, and cell cycle progression, to determine if these are linked to carnosine and melittin's anti-proliferative properties. Results: Car-NIO and Mel-NIO in vitro study inhibited cancer cell viability. They have also upregulated the expression of protein 53 (P53), BCL2-Associated X Protein (Bax), caspase-9, caspase-3, programmed cell death 4 (PDCD4), and Forkhead box O3 (FOXO3), while downregulated the expression of B-cell lymphoma 2 (Bcl2), poly (ADP-ribose) polymerase (PARP 1), and MicroRNA-183 (miRNA-183). The MCF-7 cells were arrested at the G2/M phase in Car-NIO, on the other hand, the MDA-MB-231 cells were arrested at the S phase. While the Mel- NIO and olaparib arrested the MCF-7 and MDA-MB-231 cells at the G0/1 phase. Conclusion: Our study successfully declared that Mel-NIO had more anti-cancer effects than Car-NIO in both MCF-7 and MDA-MB-231 breast cancer cells. [ABSTRACT FROM AUTHOR]

Background and purpose: Primary and metastatic breast cancers still represent an unmet clinical need for improved chemotherapy and hormone therapy. Considerable attention has been paid to natural anticancer compounds, especially lignans. The study aimed to evaluate the activity of several lignans against breast cancer cells and assess the effect of leading lignans on signaling pathways in combination with metformin. Experimental approach: Human breast cancer cell lines MCF7 (hormone-dependent), MDA-MB-231, and SKBR3 (hormone-independent) were used. A hormone-resistant MCF7/hydroxytamoxifen (HT) subline was obtained by long-term cultivation of the MCF7 line with hydroxytamoxifen. Antiproliferative activity was assessed by the MTT test; the expression of signaling pathway proteins was evaluated by immunoblotting analysis. Findings/Results: We evaluated the antiproliferative activity of lignans in breast cancer cells with different levels of hormone dependence and determined the relevant IC50 values. Honokiol was chosen as the leading compound, and its IC50 ranged from 12 to 20 µM, whereas for other tested lignans, the IC50 exceeded 50 µM. The accumulation of cleaved PARP and a decrease in the expression of Bcl-2 and ERα in MCF7/HT were induced following the combination of honokiol with metformin. Conclusions and implications: Honokiol demonstrated significant antiproliferative activity against both hormone-dependent breast cancer cells and lines with primary and acquired hormone resistance. The combination of honokiol with metformin is considered an effective approach to induce death in hormoneresistant cells. Honokiol is of interest as a natural compound with antiproliferative activity against breast cancers, including resistant tumors. [ABSTRACT FROM AUTHOR]

Purpose: Human endothelial growth factor receptor-2 (HER2) is a leucine kinase receptor that is closely related to cell growth and differentiation. It is very weakly expressed in a few epithelial cells in normal tissue. Abnormal expression of HER2 usually leads to sustained activation of downstream signaling pathways, enabling epithelial cell growth, proliferation, and differentiation; this disturbs normal physiological processes and causes tumor formation. Overexpression of HER2 is related to the occurrence and development of breast cancer. HER2 has become a well-established immunotherapy target for breast cancer. We chose to construct a second-generation CAR targeting HER 2 to test whether it kills breast cancer. Methods: We constructed a second-generation CAR molecule targeting HER2, and we generated cells expressing this second-generation CAR through lentivirus infection of T lymphocytes. LDH assay and flow cytometry were perform to detect the effect of cells and animal models. Results: The result indicated that the CARHER2 T cells could selectively kill cells with high Her2 expression. The PBMC-activated/CARHer2 cells had stronger in vivo tumor suppressive activity than PBMC-activated cells, and administration of PBMC-activated/CARHer2 cells significantly improved the survival of tumor-bearing mice, and induced the production of more Th1 cytokines in tumor-bearing NSG mice. Conclusions: We prove that the generated T cells carrying the second-generation CARHer2 molecule could effectively guide immune effector cells to identify and kill HER2-positive tumor cells and inhibit tumors in model mice. [ABSTRACT FROM AUTHOR]

Recently developed excitation frequency‐controlled cold atmospheric pressure plasma has shown its efficacy in producing tunable effects with different excitation frequencies in terms of reactive species generation and cancer cell death. This study investigates the electron number density of plasma produced at 11 kHz excitation from stark broadened Hα line, discharge characteristics through simultaneous recording of voltage‐current signals, and high‐speed images of the discharge zone. Malignant breast cancer cells (MCF‐7) and nonmalignant breast cells (MCF‐10A) were used in selectivity experiments. Proliferation and clonogenic assays revealed selective death of cancer cells. DNA damage and DNA repair kinetics were studied using time‐dependent γ‐H2AX foci formation assessment and the selective killing of cancerous cells was established for the 60 s of plasma treatment. [ABSTRACT FROM AUTHOR]