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Despite extensive research, the genes/proteins and pathways responsible for the physiological effects of estrogen remain elusive. In this study, we determined the effect of estrogen on global protein expression in breast cancer MCF7 cells using a proteomic method. The expression of 77 cytosolic, 74 nuclear, and 81 membrane/organelle proteins was significantly altered by 17-β-estradiol (E2). Protein enrichment analyses suggest that E2 may stimulate cell division primarily by promoting the G1 to S phase transition and advancing the G2/M checkpoint. The effect of E2 on cell survival was complex, as it could simultaneously enhance and inhibit apoptosis. Bioinformatics analysis suggests that E2 may enhance apoptosis by promoting the accumulation of the pore-forming protein Bax in the mitochondria and inhibit apoptosis by activating the PI3K/AKT/mTOR signaling pathway. We verified the activation of the PI3K signaling and the accumulation of Bax in the membrane/organelle fraction in E2-treated cells using immunoblotting. Treatment of MCF7 cells with E2 and the PI3K inhibitor Ly294002 significantly enhanced apoptosis compared to those treated with E2 alone, suggesting that combining estrogen with a PI3K inhibitor could be a promising strategy for treating ERα-positive breast cancer. Interestingly, many of the E2-upregulated proteins contained the HEAT, KH, and RRM domains.

Respirantins are 18-membered antimycin-type depsipeptides produced by Streptomyces sp. and Kitasatospora sp. These compounds have shown extraordinary anticancer activities against a panel of cancer cell lines with nanomolar levels of IC50 values. However, further investigation has been impeded by the low titers of the natural producers and the challenging chemical synthesis due to their structural complexity. The biosynthetic gene cluster (BGC) of respirantin was previously proposed based on a bioinformatic comparison of the four members of antimycin-type depsipeptides. In this study, we report the first successful reconstitution of respirantin in Streptomyces albus using a synthetic BGC. This heterologous system serves as an accessible platform for the production and diversification of respirantins. Through polyketide synthase pathway engineering, biocatalysis, and chemical derivatization, we generated nine respirantin compounds, including six new derivatives. Cytotoxicity screening against human MCF-7 and Hela cancer cell lines revealed a unique biphasic dose-response profile of respirantin. Furthermore, a structure-activity relationship study has elucidated the essential functional groups that contribute to its remarkable cytotoxicity. This work paves the way for respirantin-based anticancer drug discovery and development.

A series of 4-Alkyl-5-oxo-N-(pyridin-3-yl)-4,5-dihydro [1,2,3] triazolo[1,5-a] quinazoline-3-carbothioamide compounds (8a-8k) were synthesized as p38 MAP kinase inhibitors, which could potentially be used as anticancer agents. The synthesized compounds were assessed for their effectiveness in inhibiting cancer using the MCF-7 cancer cell line. The results showed that compound 8a had the highest potency, with an IC50 value of 39.76 ± 0.25 µM. Compound 8f and 8d exhibited noteworthy activity, with IC50 values of 40.43 ± 2.04 µM and 42.15 ± 2.15 µM, respectively. Compound 8a was found to effectively bind with the active site of p38α MAP kinase, with the PDB ID 1W7H. The docking score was found to be −8.8 kcal/mol. The ADME experiments, following Lipinski's rule of five and Ergan's egg graph, showed that all the synthesized compounds had excellent oral bioavailability and acceptable stomach absorption. Compound 8a stood out as the most potent drug in the series, exhibiting considerable docking affinity, ADME profile, and p38 MAP kinase inhibitory action. The findings indicated that compound 8a has promising p38 kinase inhibition and can be a possible therapeutic drug for further investigation. [ABSTRACT FROM AUTHOR]

Breast cancer is the most frequent cancer in women with a 20% mortality rate. The fate of patients suffering from breast cancer can be influenced by immune cells and tumor cells interaction in the tumor microenvironment (TME). Immune checkpoints such as Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) are regulators of the immune system and defend normal tissues from immune cell attacks but they can be expressed in breast cancer tissue and facilitate immune evasion of tumoral cells. Based on this, here we studied the role of CTLA-4 silencing by specific siRNA in MCF-7 breast cancer cell line together with Docetaxel treatment which is one of the robust chemotherapy agents to demonstrate the significance of combining chemotherapy with efficient targeted therapy in tumor regression. The MCF-7 breast cancer cell line was transfected with CTLA-4-siRNA through the electroporation method, then received an appropriate dose of Docetaxel determined by MTT assay. Flow cytometry was utilized to investigate the consequence of simultaneous CTLA-4 gene silencing and Docetaxel treatment on the apoptosis and cell cycle of MCF-7 cells. The expression levels of Bax and Bcl-2 were also investigated using quantitative real-time PCR. Compared to control groups, CTLA-4-suppressed and Docetaxel-treated cells became more susceptible to apoptosis and cell cycle arrest at the G2-M phase. The additive effect of CTLA-4 knockdown together with Docetaxel treatment significantly downregulated BCL-2 level and upregulated BAX expression. Our findings support the idea that combining chemotherapy such as Docetaxel with efficient targeted therapy against inhibitory immune checkpoints can be a promising strategy in cancer treatment. [ABSTRACT FROM AUTHOR]

Being the second leading cause of death globally, cancer has been a long-standing and rapidly evolving focus of biomedical research and practice in the world. Recently, there has been growing interest in cyanobacteria. This focus is particularly evident in developing innovative anticancer treatments to reduce reliance on traditional chemotherapy. This study investigates the anticancer potential of the Spirulina maxima extract nanoemulsion (SMNE) technique to improve the delivery, stability, and solubility of the S. maxima extract (SME). SMNE, prepared in three concentrations (SMNEC1, SMNEC2, SMNEC3), was characterized and confirmed to successfully load SME into silica-coated nanoparticles. Cytotoxicity tests on HepG2 and MCF-7 cell lines revealed a significant reduction in cell viability after 48-hour SMNE treatment, with IC50 values of 1488 µg/mL and 1721.936 µg/mL, respectively. SMNE also demonstrated efficacy in inhibiting tumor growth in mice with Ehrlich ascites carcinoma, normalizing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and reducing oxidative stress markers such as catalase (CAT) and malondialdehyde (MDA). Histopathological examination showed that SMNEC3-treated groups had almost normal liver architecture. Additionally, SMNE downregulated oncogenic miR-221-3p and miR-222-3p, activating cancer suppression genes p27 and PTEN. The study concludes that SMNE, with its anti-inflammatory and antioxidant properties and ability to modulate key miRNAs, enhances SME delivery and shows promise as an effective cancer treatment. [ABSTRACT FROM AUTHOR]

Conventional treatment strategies suffer from a lack of solubility, low bioavailability at the target site, a lack of target specificity, and indiscriminate drug distribution, all of which lead to drug resistance. Therefore, the present study aimed to deliver capsaicin into breast cancer cells through folic acid-conjugated capsaicin-loaded carboxylic acid-functionalised multiwalled carbon nanotubes (FA-CAP-COOHMWCNTs). FA-CAP-COOHMWCNTs was formulated and characterized by FTIR (Fourier transform infrared spectroscopy), SEM (Scanning electron microscopy), HR-TEM (High-resolution transmission electron microscopy), and XRD (X-ray diffraction) analysis. In silico studies demonstrated that the active molecule, capsaicin can strongly bind onto C-SRC kinase receptor to suppress cancer progression. The in vitro cellular viability of MCF-7 breast cancer cells after 24h treatment with 100 µg × mL− 1 of FA-CAP-COOHMWCNTs was found to be 29.27 ± 2.59% and IC50 value was observed to be 22.71 µg × mL− 1. Subsequently, in vivo anticancer activity of FA-CAP-COOHMWCNTs was performed against 7,12-dimethylbenz(a) anthracene (DMBA)-induced breast cancer in female Wistar rats. After 21 days of treatment with FA-CAP-COOHMWCNTs, breast cancer-induced rats showed a significant reduction in mammary tumor size, and elevated levels of antioxidant enzymes in serum/breast tissue. The most powerful antioxidant effects were seen in the medium dose (5 mg × kg− 1) of FA-CAP-COOHMWCNTs, which also caused tumors to shrink significantly, almost as much as the standard drug (doxorubicin). Histopathological studies also showed near-normal architecture of breast tissue. Altogether, it can be interpreted that FA-CAP-COOHMWCNTs have antiproliferative efficacy against breast tumor progression in breast cancer-induced rats. [ABSTRACT FROM AUTHOR]

The combination of natural and synthetic polymers for nanomedicine development had many advantages, including less toxicity, biocompatibility, prolonged circulation, higher stability, and ease of surface modification. Here, a novel folic acid-conjugated Camptothecin-loaded-poly (lactic-co-glycolic) acid-glutenin nanoparticles (FA-CPT-PLGA-Glu NPs) was fabricated to treat breast cancer. FA-CPT-PLGA-Glu NPs target breast cancer cells via upregulated folate receptors and delivered their toxic payloads without disrupting healthy cells. First, CPT-loaded PLGA NPs were created using a modified emulsification/evaporation technique. Second, Glu-based CPT-PLGA NPs were synthesized using a layer-by-layer assembly, and their physiochemical properties were validated. CPT encapsulation efficiency and loading capacity into PLGA-Glu NPs were 74.95 ± 1.34% and 4.78 ± 1.08%, respectively. CPT-PLGA-Glu NPs exhibited sustained and controlled release of loaded-CPT from NPs, and the highest content was released in an acidic environment (pH 5.3), which will be advantageous for cancer treatment. Later, FA-CPT-PLGA-Glu NPs were synthesized by simple conjugation chemistry. The fabricated FA-CPT-PLGA-Glu NPs were around 100 nm in size, with a spherical form and crystalline nature. FA-CPT-PLGA-Glu NPs show strong cytotoxicity activity, and its IC50 value was 16.33 µg × mL− 1 against breast cancer cell line (MCF-7). This folate-receptor-targeted NPs are more effectively internalized into MCF-7 cells, causing ROS generation, cell growth inhibition, and apoptosis. The activity of caspase-3 and − 9 causes MCF-7 cells apoptosis by internalized CPT. Further, internalized CPT induces potential loss of mitochondrial transmembrane and damages the nuclear integrity of the cancer cells. These results showed that the FA-CPT-PLGA-Glu NPs target upregulated folate receptors on the surface of MCF-7 cells.. [ABSTRACT FROM AUTHOR]

Derivatives of the potassium-sparing diuretic amiloride are preferentially cytotoxic toward tumor cells relative to normal cells, and have the capacity to target tumor cell populations resistant to currently employed therapeutic agents. However, a major barrier to clinical translation of the amilorides is their modest cytotoxic potency, with estimated IC50 values in the high micromolar range. Here we report the synthesis of ten novel amiloride derivatives and the characterization of their cytotoxic potency toward MCF7 (ER/PR-positive), SKBR3 (HER2-positive) and MDA-MB-231 (triple negative) cell line models of breast cancer. Comparisons of derivative structure with cytotoxic potency toward these cell lines underscore the importance of an intact guanidine group, and uncover a strong link between drug-induced cytotoxicity and drug lipophilicity. We demonstrate that our most potent derivative called LLC1 is preferentially cytotoxic toward mouse mammary tumor over normal epithelial organoids, acts in the single digit micromolar range on breast cancer cell line models representing all major subtypes, acts on cell lines that exhibit both transient and sustained resistance to chemotherapeutic agents, but exhibits limited anti-tumor effects in a mouse model of metastatic breast cancer. Nonetheless, our observations offer a roadmap for the future optimization of amiloride-based compounds with preferential cytotoxicity toward breast tumor cells.

Single cancer cells within a tumor exhibit variable levels of resistance to drugs, ultimately leading to treatment failures. While tumor heterogeneity is recognized as a major obstacle to cancer therapy, standard dose-response measurements for the potency of targeted kinase inhibitors aggregate populations of cells, obscuring intercellular variations in responses. In this work, we develop an analytical and experimental framework to quantify and model dose responses of individual cancer cells to drugs. We first explore the connection between population and single-cell dose responses using a computational model, revealing that multiple heterogeneous populations can yield nearly identical population dose responses. We demonstrate that a single-cell analysis method, which we term a threshold inhibition surface, can differentiate among these populations. To demonstrate the applicability of this method, we develop a dose-titration assay to measure dose responses in single cells. We apply this assay to breast cancer cells responding to phosphatidylinositol-3-kinase inhibition (PI3Ki), using clinically relevant PI3Kis on breast cancer cell lines expressing fluorescent biosensors for kinase activity. We demonstrate that MCF-7 breast cancer cells exhibit heterogeneous dose responses with some cells requiring over ten-fold higher concentrations than the population average to achieve inhibition. Our work reimagines dose-response relationships for cancer drugs in an emerging paradigm of single-cell tumor heterogeneity.

Manuka honey (MH) exhibits potential antitumor activity in preclinical models of a number of human cancers. Treatment in vitro with MH at concentrations ranging from 0.3 to 5.0% (w/v) led to significant dose-dependent inhibition of proliferation of human breast cancer MCF-7 cells, but anti-proliferative effects of MH were less pronounced in MDA-MB-231 breast cancer cells. Effects of MH were also tested on non-malignant human mammary epithelial cells (HMECs) at 2.5% w/v, and it was found that MH reduced the proliferation of MCF-7 cells but not that of HMECs. Notably, the antitumor activity of MH was in the range of that exerted by treatment of MCF-7 cells with the antiestrogen tamoxifen. Further, MH treatment stimulated apoptosis of MCF-7 cells in vitro, with most cells exhibiting acute and significant levels of apoptosis that correlated with PARP activation. Additionally, the effects of MH induced the activation of AMPK and inhibition of AKT/mTOR downstream signaling. Treatment of MCF7 cells with increased concentrations of MH induced AMPK phosphorylation in a dose-dependent manner that was accompanied by inhibition of phosphorylation of AKT and mTOR downstream effector protein S6. In addition, MH reduced phosphorylated STAT3 levels in vitro, which may correlate with MH and AMPK-mediated anti-inflammatory properties. Further, in vivo, MH administered alone significantly inhibited the growth of established MCF-7 tumors in nude mice by 84%, resulting in an observable reduction in tumor volume. Our findings highlight the need for further research into the use of natural compounds, such as MH, for antitumor efficacy and potential chemoprevention and investigation of molecular pathways underlying these actions.

Studies have been done on salicin (SA), which is a strong anti-inflammatory. Angiogenesis is an important mechanism for the growth of cancer, and inhibiting it is an effective antitumor treatment method. However, its widespread use in treating cancer is constrained by its poor bioavailability at tumor locations and inferior pharmacokinetics. The present investigation aimed to synthesize salicin-loaded nanoparticles (SANPs) and evaluate the antitumor potential of the SANPs using human MCF-7 cancer cells. SANPs were developed using the nanoprecipitation method, and they were examined using a transmission electron microscope (TEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) techniques, and differential scanning calorimetry (DSC). SANPs provide a persistent pattern of drug delivery, as shown by the UV spectroscopic measurement of the in vitro drug release. SANPs were discovered to be more cytotoxic than free SA in MCF-7 cells using an MTT-based colorimetric test. In addition, in contrast to treatment with free SA in MCF-7 cells, treatment with SANPs dramatically enhanced the lipid peroxidation status (TBARS) values (P < 0.05) and intracellular ROS, and lowered GSH levels. Additionally, it was found that cancer cells had considerably changed apoptotic indicators, such as nuclear fragmentation and membrane blebbing, and mitochondrial membrane potential after being treated with SANPs. Together, the current study shows that the produced SANPs and free SA have anticancer potential in vitro in breast cancer cells. [ABSTRACT FROM AUTHOR]

Abstract In this work, we reported the synthesis of honey bee (Apis mellifera) venom-derived nanoparticles via a hydrothermal method. This method not only ensures the preservation of the bee venom’s bioactive components but also enhances their potential stability, thus broadening the scope for their applications in the biomedicinal field. The synthesis method started with the homogenization suspension of bee venom, followed by its hydrothermal process to synthesize bee venom nanoparticles (BVNPs). The successful synthesis of BVNPs was characterized using various characteristic techniques such as Ultraviolet–visible (UV–Vis) spectroscopy, Fourier Transforms Infrared (FTIR) Spectroscopy, Zeta Potential (ZP), Liquid Chromatography-Mass Spectrometry (LCMS), and Transmission Electron Microscopy (TEM). The synthesis of BVNPs through biosynthesis is shown by the visible violet-brown color development at 347 nm by UV–Vis spectroscopy. FTIR analysis revealed the presence of several functional groups in the BVNPs, including alcohols (–OH), phenols (C6H5–), carboxylic acids (–COOH), amines (–NH2, –NH–), aldehydes (–CHO), ketones (–CO–), nitriles (–CN), amides (–CO–N–), imines (–CNH–), esters (–COO–), and polysaccharides. These functional groups, as confirmed by their specific stretching and bending vibrational modes, contribute to the diverse biological activities of BVNPs, including cytotoxicity against MCF-7 breast cancer cells. The ZP of the BVNPs indicated good colloidal stability at − 45 mV. LCMS analysis confirmed the presence of major bioactive molecules, including melittin & apamin and TEM analysis shows the BVNPs exhibited a quasi-spherical shape with good dispersion, the average size was approximately 25 nm, with some being smaller (quantum dots) and interplanar spacing of 0.236 nm indicated a highly ordered crystalline structure. Moreover, the anticancer efficacy of the BVNPs was ascertained through in vitro assays against MCF-7 breast cancer cells, showing a dose-dependent cytotoxic effect. The findings of this study underscore the viability of hydrothermal synthesis in producing biologically active and structurally stable BVNPs, with a significant potential for anticancer activities. Graphical Abstract

Green synthesis of nanoparticles through biogenic methods and plant secondary metabolites has gained significant importance due to their faster reduction rates, making them a more environmentally friendly and cost-effective alternative to traditional chemical and physical methods. This study presents a sustainable method for synthesizing fluorescent ZnS nanocrystals using Allium sativum extract. The synthesis utilizes sulfur-rich cysteine compounds and templating agents such as alkaloids and flavonoids of the Allium sativum extract. The resulting ZnS NPs were characterized using X-ray diffraction (XRD), UV–Vis spectroscopy, photoluminescence spectroscopy, while FE-SEM revealed an average particle size of 128nm and TEM showed particle size in the range of 42–78nm. The optical investigations reports showed that the biosynthesized ZnS NPs had an energy band gap of 4.9eV with absorption and excitation wavelengths of 214nm and 460nm, respectively. In vitro cytotoxicity assays showed significant anticancer activity against MCF-7 human breast cancer cells, with an IC50 value of 58.2μg/mL. [ABSTRACT FROM AUTHOR]

Apigenin (API), a traditionally sourced flavonoid, is recognized for its anti-neoplastic properties. Despite well-documented effects on tumorigenesis, the detailed therapeutic impact on breast cancer stem cells (BCSCs) and the associated molecular mechanisms are yet to be clarified. The objective of this study is to elucidate the therapeutic effects of API on BCSCs and to uncover its molecular mechanisms through network pharmacology and experimental validation. Interactions of API with candidate targets were examined through target screening, enrichment analysis, construction of protein-protein interaction networks, and molecular docking. MCF-7-derived BCSCs were utilized as a model system to investigate and substantiate the anti-BCSC effects of API and the underlying mechanism. Molecular docking studies have shown that API and TP53 exhibit favorable binding affinity. Compared with the negative control group, API effectively suppressed the expression of BCSC-related proteins such as ALDH1A1, NANOG, EpCAM, and MYC, downregulated p-PI3K and p-AKT, and upregulated p53. This study demonstrates that API can play an anti-BCSC role by regulating the PI3K/AKT/p53 pathway in BCSCs of MCF-7 cells, highlighting its potential as a therapeutic agent for targeting BCSCs. [ABSTRACT FROM AUTHOR]

Ectophosphatases catalyse the hydrolysis of phosphorylated molecules, such as phospho‐amino acids, in the extracellular environment. Nevertheless, the hydrolysis of nucleotides in the extracellular environment is typically catalysed by ectonucleotidases. Studies have shown that acid ectophosphatase, or transmembrane‐prostatic acid phosphatase (TM‐PAP), a membrane‐bound splice variant of prostatic acid phosphatase, has ecto‐5′‐nucleotidase activity. Furthermore, it was demonstrated that ectophosphatase cannot hydrolyse ATP, ADP, or AMP in triple‐negative breast cancer cells. In contrast to previous findings in MDA‐MB‐231 cells, the ectophosphatase studied in the present work displayed a remarkable capacity to hydrolyse AMP in luminal A breast cancer cells (MCF‐7). We showed that AMP dose‐dependently inhibited p‐nitrophenylphosphate (p‐NPP) hydrolysis. The p‐NPP and AMP hydrolysis showed similar biochemical behaviours, such as increased hydrolysis under acidic conditions and comparable inhibition by NiCl2, ammonium molybdate, and sodium orthovanadate. In addition, this ectophosphatase with ectonucleotidase activity was essential for the release of adenosine and inorganic phosphate from phosphorylated molecules available in the extracellular microenvironment. This is the first study to show that prostatic acid phosphatase on the membrane surface of breast cancer cells (MCF‐7) is correlated with cell adhesion and migration. Highlights: A transmembrane prostatic acid phosphatase (TM‐PAP) is expressed in luminal A MCF‐7 breast cancer cells.Ectonucleotidase activity by TM‐PAP was observed in MCF‐7 cells.The presence of prostatic acid phosphatase on the membrane surface is correlated with cell adhesion and migration. [ABSTRACT FROM AUTHOR]

The present work aimed to find out a novel agent for green synthesized zinc oxide nanoparticles (ZnONPs) from the fresh fruity bodies of edible mushroom (Hypsizygus ulmarius), and it was characterized by UV–Vis, XRD, HR-TEM, SEM, FT-IR, EDX, PSA, and Zeta potential analysis. UV–Vis spectra result reflects a typical absorption peak at 260 nm due to their significant excitation binding energy at room temperature. The chemical bond formation from the zinc oxide was confirmed by FT-IR analysis. XRD results revealed the hexagonal structure, and SEM analyses reflected the spherical shape ZnONPs with an average size of 27.10 nm. The outcome of the EDX spectrum confirmed the high purity of synthesized ZnONPs, and the zeta potential value indicates the aggregation of particles with good quality. The Hu-ZnONPs expressed a better larval toxicity effect against Culex quinquefasciatus (IVth instar larvae) with the least LC50 and LC90 values (21.52, 121.70 mg/L) after 24 h treatment. For the antibacterial assay, the maximum growth inhibition zone was recorded in S. aureus (14.2 ± 0.2), E. coli (10.1 ± 0.3), and K. pneumoniae (9.0 ± 0.1 mm). The anticancer assay results expressed a significant level of toxic effects (LC50 values 29.07 μg/ml) of Hu-ZnONPs against the MCF-7 breast cancer cells, even at a very low dose. The study's findings suggest that the H. ulmarius can biosynthesize ZnONPs and could be an alternative biomedical agent for future therapeutic applications. [ABSTRACT FROM AUTHOR]

In this work, we reported the synthesis of honey bee (Apis mellifera) venom-derived nanoparticles via a hydrothermal method. This method not only ensures the preservation of the bee venom's bioactive components but also enhances their potential stability, thus broadening the scope for their applications in the biomedicinal field. The synthesis method started with the homogenization suspension of bee venom, followed by its hydrothermal process to synthesize bee venom nanoparticles (BVNPs). The successful synthesis of BVNPs was characterized using various characteristic techniques such as Ultraviolet–visible (UV–Vis) spectroscopy, Fourier Transforms Infrared (FTIR) Spectroscopy, Zeta Potential (ZP), Liquid Chromatography-Mass Spectrometry (LCMS), and Transmission Electron Microscopy (TEM). The synthesis of BVNPs through biosynthesis is shown by the visible violet-brown color development at 347 nm by UV–Vis spectroscopy. FTIR analysis revealed the presence of several functional groups in the BVNPs, including alcohols (–OH), phenols (C6H5–), carboxylic acids (–COOH), amines (–NH2, –NH–), aldehydes (–CHO), ketones (–CO–), nitriles (–CN), amides (–CO–N–), imines (–CNH–), esters (–COO–), and polysaccharides. These functional groups, as confirmed by their specific stretching and bending vibrational modes, contribute to the diverse biological activities of BVNPs, including cytotoxicity against MCF-7 breast cancer cells. The ZP of the BVNPs indicated good colloidal stability at − 45 mV. LCMS analysis confirmed the presence of major bioactive molecules, including melittin & apamin and TEM analysis shows the BVNPs exhibited a quasi-spherical shape with good dispersion, the average size was approximately 25 nm, with some being smaller (quantum dots) and interplanar spacing of 0.236 nm indicated a highly ordered crystalline structure. Moreover, the anticancer efficacy of the BVNPs was ascertained through in vitro assays against MCF-7 breast cancer cells, showing a dose-dependent cytotoxic effect. The findings of this study underscore the viability of hydrothermal synthesis in producing biologically active and structurally stable BVNPs, with a significant potential for anticancer activities. [ABSTRACT FROM AUTHOR]

A new colorimetric and fluorescence turn‐on chemodosimeter for selective detection of GSH over Cys and Hcy with 34‐fold enhancement in emission intensity is reported. Probe 1 exhibited ultra‐sensitivity toward GSH with 0.125 nM detection limit and successfully displayed GSH detection in MCF‐7 live cells. The mechanism of sensing is established by density functional theoretical calculations. [ABSTRACT FROM AUTHOR]

Background: Cancer is the most lethal disease in humans, accounting for one out of every six fatalities. The most frequent type of cancer among women is breast cancer, followed by cervix cancer. Iron oxide nanoparticles, due to their superparamagnetic traits, are one of the most widely used nanomaterials for diagnosing and treating breast cancer. For site-specific medication delivery, biotin was coupled with magnetite nanoparticles. Materials and Methods: The dextran-coated IONP was synthesized by a simple coprecipitation process and biotin was attached to the surface of dextran via a carboxylic/amine group. X-ray Diffractometer, Thermal gravimetric Analysis, Fourier Transformed Infrared Spectrometer, Atomic Force Microscopy and Vibrating Sample Magnetometer were used to investigate the structural, morphological, and magnetic properties of the produced materials. Results and Discussion: The iron oxide nanoparticle particle size was determined to be 325 nm. The MTT assay of IONPs and dextran-coated biotin-conjugated IONPs with low IC50 values of 24.18 μg/mL and 1.66 μg/mL exhibit cytotoxicity toxicity against MCF 7 cells, whereas the cytotoxicity of biotin-linked IONPs higher when compared with pure iron oxide. Conclusion: Iron oxide nanoparticle and dextran-coated biotin-conjugated iron oxide nanoparticle results confirmed the anti-breast cancer efficacy on human breast cancer cells by causing effective cytotoxicity and ensuring the drug delivery to a specific site. [ABSTRACT FROM AUTHOR]

The combination therapy, which has garnered significant interest for its potential to enhance therapeutic success compared to single-drug therapy. The investigation centers on the fabrication of reduced graphene oxide-alginate microbeads for the co-delivery and controlled release of doxorubicin (DOX) and 5-fluorouracil (5-FU). The anticancer activity of the developed microbeads is assessed against MCF-7 cells using an MTT assay, indicating promising results for dual-drugcontaining microbeads. [ABSTRACT FROM AUTHOR]

This study aimed to develop paclitaxel (PTX)-loaded PEGylated (PEG)-pH-sensitive (SpH) liposomes to enhance drug delivery efficiency and cytotoxicity against MCF-7 breast cancer cells. PTX-loaded PEG-SpH liposomes were prepared using the thin film hydration method. ATR-FTIR compatibility studies revealed no significant interactions among liposome formulation components. TEM images confirmed spherical morphology, stability, and an ideal size range (180–200 nm) for improved blood circulation. At pH 5.5, liposomes exhibited increased size and positive zeta potential, indicating pH-sensitive properties due to CHEMS response to the acidic tumor microenvironment. Conversely, at pH 7.4, liposomes showed a slightly larger size (199.25 ± 1.64 nm) and a more negative zeta potential (-36.94 ± 0.32 mV), suggesting successful PEG-SpH surface modification, enhancing stability, and reducing aggregation. PTX-loaded PEG-SpH liposomes demonstrated high encapsulation efficiency (84.57 ± 0.92% w/w) and drug loading capacity (4.12 ± 0.26% w/w). In-vitro drug release studies revealed accelerated first-order PTX release at pH 5.5 and a controlled zero-order release at pH 7.4. Cellular uptake studies on MCF-7 cells demonstrated enhanced PTX uptake, attributed to mPEG-PCL incorporation prolonging circulation time and CHEMS facilitating PTX release in the tumor microenvironment. Furthermore, PTX-loaded PEG-SpH liposomes exhibited significantly improved cytotoxicity with an IC50 value of 1.107 µM after 72-h incubation, approximately 90% lower than plain PTX solution. Stability studies confirmed the robustness of the liposomal formulation under various storage conditions. These findings highlight the potential of PEGylated pH-responsive liposomes as effective nanocarriers for enhancing PTX therapy against breast cancer. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective: Considering that the αvβ3 integrin plays an important role in tumor metastasis, this study investigated the involvement of these pathways in mediating the triiodothyronine (T3) effects on amphiregulin (AREG) expression. Materials and methods: We treated MCF-7 cells with T3 (10 nM) for 1 hour in the presence or absence of inhibitors for αvβ3 integrin (RGD peptide), MAPK (PD98059), PI3K (LY294002), and protein synthesis (cycloheximide [CHX]). A control group (C) received no T3 or inhibitors. Analyses of mRNA and protein expression were done using RT-qPCR and Western blot, respectively. Results: We observed that T3 increased AREG expression, an effect that was suppressed by all inhibitors. This finding indicates that the activation of the αvβ3 integrin signaling pathway, via PI3K, MAPK/ERK, is necessary for the T3-mediated effects on AREG expression and highlights the involvement of nongenomic mechanisms. In addition, CHX completely abolished T3-induced AREG mRNA expression, indicating that this effect requires prior protein synthesis. Conclusion: The identification that T3 acts through this signaling pathway holds considerable potential for clinical application, as it could lead to the development of specific drugs to block it.

The magnetic biocompatible Fe3O4@Agar-Ag catalyst was designed and prepared based on a natural macromolecule (agar) through a convenient method using inexpensive, nontoxic, and easily available substances. Following synthesis, the catalyst underwent characterization using various techniques such as FT-IR, XRD, FE-SEM, EDX, VSM, TGA, and ICP. Subsequently, its efficacy was evaluated in treating breast cancer, in vitro. The results demonstrated the catalyst's effectiveness in reducing the proliferation of MCF-7 cells, suggesting its potential as an anticancer agent. Furthermore, our findings highlighted the biocompatibility of the synthesized nanoparticle and its lower toxicity toward normal cells. [ABSTRACT FROM AUTHOR]

Greener fabrication of nanostructures has received remarkable attention due to their sustainability, cost-effectiveness, simplicity, and eco-friendliness. Opuntia ficus-indica-derived mucilage has not been exposed well to fabricate nanostructures. Thus, in this present investigation, we successfully synthesized tungsten trioxide (WO3) nanostructures using Opuntia ficus-indica-derived mucilage as bio-templates because it is more economical and environmentally friendly. Also, the fabricated WO3 nanostructures cytotoxic features and their photothermal effects were studied. The WO3 nanostructures were investigated using diverse analytical instruments: X-ray diffractometer (XRD), scanning electron microscope and, transmission electron microscope. Based on the structural and morphological characteristics of the WO3 nanostructures, they have sphere-like morphologies with diameters of 100 - 200 nm. As revealed by XRD, monoclinic crystalline WO3 nanostructures were formed. In vitro assays were used to assess the effect of WO3 nanostructures on cell viability and morphological features of cells. Based on in vitro assays, fabricated WO3 nanostructures showed slightly toxic behaviour in a human breast cancer cell line (MCF-7 cells). In contrast, after exposure to NIR lasers, the viability of WO3 nanostructures treated cells decreased significantly. Because the WO3 nanostructures have an excellent photothermal effect, which triggers cell death in cancer cells. Thus, the fabricated WO3 nanostructures can be used as a photothermal agent for cancer therapy [ABSTRACT FROM AUTHOR]

Doxorubicin is the first-line chemotherapy agent for breast cancer treatment. However, it's reported to cause cardiotoxicity and induce chemoresistance in breast cancer cells. Doxorubicin is able to induce Pgp (P-glycoprotein) overexpression through NF-kB activation resulting in efflux of chemotherapeutic agents in MCF-7 cells. One of the approaches being developed for cancer treatment is combination therapy by combining two or more anticancer agents that may reduce side effects and provide better effects than single therapy. Peperomia pellucida is reported to have anticancer activity and is widely used as a traditional medicine. This study aimed to investigate the cytotoxic activity of the n-hexane fraction of Peperomia pellucida (NFP) and its combination with doxorubicin (D) against MCF-7 cells. The selectivity of NFP was evaluated using vero cells as a comparator. The phytochemical properties of NFP were evaluated using TLC and LC-MS/MS methods. The cytotoxic activity was determined using the MTT assay. Combination Index (CI) calculations were performed to determine the effect of the combination. This study found that NFP contained about 30 identified compounds and had an IC 50 of 96.68 ppm, while doxorubicin had an IC 50 of 2.10 ppm. The combination of 24.2 ppm (1/4 IC 50) of NFP with 0.26 ppm (1/8 IC 50) of doxorubicin had a synergistic cytotoxic effect (CI=0.6) against MCF-7 cells. NFP was selective for MCF-7 cells with a selectivity index of 21.83. The results suggest that NFP may have the potential to enhance the therapeutic efficacy of doxorubicin in breast cancer treatment. [Display omitted] • The N-hexane fraction of Peperomia pellucida (NFP) contained about 30 identified compounds, including ß-sitosterol and stigmasterol. • The N-hexane fraction of Peperomia pellucida (NFP) was selective for MCF-7 cells with IC 50 of 96,68. • The combination of the N-hexane fraction of Peperomia pellucida (NFP) (1/4 IC 50) with doxorubicin (1/8 IC 50) had a synergistic effect with a CI value of 0.6 and increased cytotoxic activity against MCF-7 cells. [ABSTRACT FROM AUTHOR]

The treatment of cancer often leads to a range of adverse effects. Encapsulating drugs can mitigate these effects and enhance drug efficacy by enabling a controlled release at the site of interest. This study details the successful synthesis of zinc oxide nanoparticles (ZnONPs) through the precipitation of Zn(NO3)2·6H2O with KOH. A Pd(II) complex drug was synthesized from a Schiff base ligand derived from 2-hydroxybenzohydrazide and (E)-1-(2-(p-tolyl)hydrazono)propan-2-one using potassium tetrachloropalladate(II). This complex was subsequently incorporated into ZnONPs. Characterization of the resulting compounds was performed using Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), Zeta Potential, Fourier Transform Infrared (FTIR) Spectroscopy, and UV-visible spectroscopy. TEM imaging revealed particle sizes of 160.69 ± 4.74 nm for ZnONPs and 185.28 ± 2.3 nm for the Pd(II) complex-encapsulated ZnONPs. The Zeta potential values were 6.53 mV for ZnONPs and 7.36 mV for Pd(II) complex-encapsulated ZnONPs. UV-visible spectroscopy showed an absorption peak at 360 nm for ZnONPs, while the Pd(II) complex-encapsulated ZnONPs exhibited a peak at 410 nm. FTIR analysis indicated the presence of the Pd(II) complex within the ZnONPs, as evidenced by a consistent Zn-O vibrational band at 832 cm−1 and a shift in another peak from 460 to 413 cm−1. Additionally, the detection of a C = N stretching vibration at 1548 cm-1 and a carbonyl stretch at 1626 cm−1 was observed. The Encapsulation Efficiency (E.E.) of the Pd(II) complex was 97.2%. A drug release experiment conducted at pH 7 showed a steady-state release pattern after 16 h, with a cumulative release of 44.3%. The cytotoxic effects of the Pd(II) complex and its encapsulated form in ZnONPs on the MCF-7 cell line were assessed via MTT test. The Pd(II) complex encapsulated within ZnONPs exhibited decreased toxicity relative to the unencapsulated drug, as evidenced by a higher IC50 value of 418.5 μg/ml. This suggests that the encapsulation facilitates a sustained release, which allows for targeted accumulation within cells. The elevated IC50 value indicates that the drug delivery system may be engineered to modulate the release of the drug in a more controlled manner, potentially resulting in a prolonged release profile rather than an immediate therapeutic impact. [ABSTRACT FROM AUTHOR]

Peganum harmala has been extensively employed in Algerian traditional medicine practices. This study aimed to explore the impact of n-butanol (n-BuOH) extract sourced from Peganum harmala seeds on cell proliferation, cell migration, and angiogenesis inhibition. Cytotoxic potential of n-BuOH extract was evaluated using MTT (3-(4,5-dimethylthiazol-2-yl) 2,5 diphenyltetrazolium bromide) assay against human breast adenocarcinoma MCF-7 cells, cell migration was determined using scratch assay, and anti-angiogenic effect was evaluated through macroscopic and histological examinations conducted on chick embryo chorioallantoic membrane. Additionally, this research estimated the phytochemical profile of n-BuOH extract. Fifteen phenolic compounds were identified using Ultra-performance liquid chromatography UPLC-ESI-MS-MS analysis. In addition, the n-BuOH extract of P. harmala exhibited potent antioxidant and free radical scavenging properties. The n-BuOH extract showed potent cytotoxicity against MCF-7 cell with an IC50 value of 8.68 ± 1.58 μg/mL. Furthermore, n-BuOH extract significantly reduced migration. A strong anti-angiogenic activity was observed in the groups treated with n-BuOH extract in comparison to the negative control. Histological analysis confirmed the anti-angiogenic effect of the n-BuOH extract. This activity is probably a result of the synergistic effects produced by different polyphenolic classes. [ABSTRACT FROM AUTHOR]

Apigenin (API), a traditionally sourced flavonoid, is recognized for its anti-neoplastic properties. Despite well-documented effects on tumorigenesis, the detailed therapeutic impact on breast cancer stem cells (BCSCs) and the associated molecular mechanisms are yet to be clarified. The objective of this study is to elucidate the therapeutic effects of API on BCSCs and to uncover its molecular mechanisms through network pharmacology and experimental validation. Interactions of API with candidate targets were examined through target screening, enrichment analysis, construction of protein-protein interaction networks, and molecular docking. MCF-7-derived BCSCs were utilized as a model system to investigate and substantiate the anti-BCSC effects of API and the underlying mechanism. Molecular docking studies have shown that API and TP53 exhibit favorable binding affinity. Compared with the negative control group, API effectively suppressed the expression of BCSC-related proteins such as ALDH1A1, NANOG, EpCAM, and MYC, downregulated p-PI3K and p-AKT, and upregulated p53. This study demonstrates that API can play an anti-BCSC role by regulating the PI3K/AKT/p53 pathway in BCSCs of MCF-7 cells, highlighting its potential as a therapeutic agent for targeting BCSCs.

Royal jelly (RJ) is rich in various nutrients, including proteins and amino acids. RJ consumption improves sexual and urinary function in postmenopausal women, possibly owing to its hormone-like effects. Currently, hormone regulation and assisted reproductive technologies are widely used to treat thin endometria; however, high doses of these drugs can add to liver burden. In this study, RJ proteins and fatty acids were isolated, and their therapeutic effects on thin endometria were investigated in vivo and in vitro to verify their hormone-like regulatory effects. The results showed that RJ and its extracts could regulate endometrial receptivity-related factor expression levels in rats with a thin endometrium, accelerate MCF-7 cell apoptosis, and increase estrogen receptor expression in MCF-7 cells wherein. The estrogen-like effects of RJ and the fatty acids may be the main contributors. RJ may be a potential natural hormone replacement therapy.

Abstract Silver nanoparticles (AgNPs) have gained much attention due to their unique physical, and chemical properties. Integration of phytochemicals in nanoformulation might have higher applicability in healthcare. Current work demonstrates the synthesis of green AgNPs with O. gratissimum (gr-AgNPs) O. tenuiflorum (te-AgNPs) and O. americanum (am-AgNPs) followed by an evaluation of their antimicrobial and anticancer properties. SEM analysis revealed spherical-shaped particles with average particle sizes of 69.0 ± 5 nm for te-AgNPs, 46.9 ± 9 nm for gr-AgNPs, and 58.5 ± 18.7 nm for am-AgNPs with a polydispersity index below 0.4. The synthesized am-AgNPs effectively inhibited Klebsiella pneumonia , Escherichia coli , Staphylococcus aureus, Aspergillus niger, and Candida albicans with 23 ± 1.58 mm, 20 ± 1.68 mm, 22 ± 1.80 mm, 26 ± 1.85 mm, and 22 ± 1.40 nm of zone of inhibition respectively. Synthesized AgNPs also induced apoptotic cell death in MCF-7 in concentration-dependent manner. IC50 values for am-AgNPs, te-AgNPs, and gr-AgNPs were 14.78 ± 0.89 µg, 18.04 ± 0.63 and 15.41 ± 0.37 µg respectively which suggested that am-AgNPs were the most effective against cancer. At higher dose size (20 µg) AgNPs were equally effective to commercial standard Doxorubicin (DOX). In comparison to te-AgNPs and gr-AgNPs, am-AgNPs have higher in vitro anticancer and antimicrobial effects. The work reported Ocimum americanum for its anticancer properties with chemical profile (GCMS) and compared it with earlier reported species. The activity against microbial pathogens and selected cancer cells clearly depicted that these species have distinct variations in activity. The results have also emphasized on higher potential of biogenic silver nanoparticles in healthcare but before formulation of commercial products, detailed analysis is required with human and animal models.

Radiation therapy benefits more than 50% of all cancer patients and cures 40% of them, where ionizing radiation (IR) deposits energy to cells and tissues, thereby eliciting DNA damage and resulting in cell death. Small GTPases are a superfamily of proteins that play critical roles in cell signaling. Several small GTPases, including RAC1, RHOB, and RALA, were previously shown to modulate radioresistance in cancer cells. However, there is no systematic proteomic study on small GTPases that regulate radioresistance in cancer cells. Herein, we applied a high-throughput scheduled multiple-reaction monitoring (MRM) method, along with the use of synthetic stable isotope-labeled (SIL) peptides, to identify differentially expressed small GTPase proteins in two pairs of breast cancer cell lines, MDA-MB-231 and MCF7, and their corresponding radioresistant cell lines. We identified 7 commonly altered small GTPase proteins with over 1.5-fold changes in the two pairs of cell lines. We also discovered ARFRP1 as a novel regulator of radioresistance, where its downregulation promotes radioresistance in breast cancer cells. Together, this represents the first comprehensive investigation about the differential expression of the small GTPase proteome associated with the development of radioresistance in breast cancer cells. Our work also uncovered ARFRP1 as a new target for enhancing radiation sensitivity in breast cancer.

[Display omitted] The excessive secretion of H 2 O 2 within cells is closely associated with cellular dysfunction. Therefore, high sensitivity in situ detection of H 2 O 2 released from living cells was valuable in clinical diagnosis. In the present work, a novel electrochemical cells sensing platform by synthesizing copper nanoclusters (CuNCs) at room temperature based on DNA nanoribbon (DNR) as a template (DNR-CuNCs). The tight and ordered arrangement of nanostructured assemblies of DNR-CuNCs conferred the sensor with superior stability (45 days) and electrochemical performance. The MUC1 aptamer extending from the DNR template enabled the direct capture MCF-7 cells on electrode surface, this facilitated real-time monitoring of H 2 O 2 release from stimulated MCF-7 cells. While the captured MCF-7 cells on the electrode surface significantly amplified the current signal of H 2 O 2 release compared with the traditional electrochemical detection H 2 O 2 released signal by MCF-7 cells in PBS solution. The approach provides an effective strategy for the design of versatile sensors and achieving monitored cell release of H 2 O 2 in long time horizon (10 h). Thereby expanding the possibilities for detecting biomolecules from live cells in clinical diagnosis and biomedical applications. [ABSTRACT FROM AUTHOR]

Breast cancer is a leading cause of cancer-related deaths among women. Cisplatin is used for treatment, but the development of resistance in cancer cells is a significant concern. This study aimed to investigate changes in the transcriptomes of cisplatin-resistant MCF7 cells. We conducted RNA sequencing of cisplatin-resistant MCF7 cells, followed by differential expression analysis and bioinformatic investigations to identify changes in gene expression and modified signal transduction pathways. We examined the size and quantity of extracellular vesicles. A total of 724 genes exhibited differential expression, predominantly consisting of protein-coding RNAs. Notably, two long non-coding RNAs (lncRNAs), NEAT1 and MALAT, were found to be dysregulated. Bioinformatic analysis unveiled dysregulation in processes related to DNA synthesis and repair, cell cycle regulation, immune response, and cellular communication. Additionally, modifications were observed in events associated with extracellular vesicles. Conditioned media from resistant cells conferred resistance to wild-type cells in vitro. Furthermore, there was an increase in the number of vesicles in cisplatin-resistant cells. Cisplatin-resistant MCF7 cells displayed differential RNA expression, including the dysregulation of NEAT1 and MALAT long non-coding RNAs. Key processes related to DNA and extracellular vesicles were found to be altered. The increased number of extracellular vesicles in resistant cells may contribute to acquired resistance in wild-type cells. [ABSTRACT FROM AUTHOR]

Purpose: Cancer, the second leading cause of mortality worldwide, represents a global health challenge, primarily due to drug resistance. Vinorelbine is a chemotherapeutic agent that disrupts cancer cell growth by targeting microtubules and inducing apoptosis. However, drug resistance remains a formidable obstacle. This resistance is caused by various factors including genetic mutations, drug efflux mechanisms, and DNA repair systems. Resolution of this challenge requires an innovative approach. This study investigated the potential of small interfering RNA (siRNA) to target and downregulate a vinorelbine-resistant MCF-7/ADR breast cancer cell line. Methods: Cells were cultured in Dulbecco's modified Eagle's medium (DMEM) 10% fetal bovine serum/penicillin/streptomycin. An siRNA targeting ABCB1 was designed and synthesized, and the cells were transfected with siRNA at final concentrations of 10, 20, and 30 nM. The3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess cell viability. ABCB1 mRNA expression levels were determined by real-time polymerase chain reaction (PCR). Results: MCF-7 cells exhibited a higher sensitivity to vinorelbine than MCF-7/ADR cells. MCF-7/ADR cells exhibited resistance to vinorelbine at concentrations, 12.50 and 25.00 μM. Treatment with siRNA significantly reduced ABCB1 expression by 2.93-fold (P =0.0001). Similarly, co-treatment with siRNA and vinorelbine produced a substantial 2.89-fold decrease in ABCB1 gene expression in MCF-7 cells compared to that in MCF-7/ADR cells (P =0.0001). Conclusion: The results of the present study indicate that the concurrent use of siRNA and vinorelbine holds substantial promise as a therapeutic approach to overcome ABCB1-mediated multidrug resistance (MDR) in breast cancer. It is necessary to conduct comprehensive clinical trials to determine the true effectiveness of this combination therapy. [ABSTRACT FROM AUTHOR]

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This work reports a new ATP-independent bioluminescent probe (bor-DTZ) for detecting hydrogen peroxide that is compatible with the Nanoluciferase enzyme. The probe is designed with an arylboronate ester protecting group appended to a diphenylterazine core via a self-immolative phenolate linker. Reaction with hydrogen peroxide reveals diphenylterazine, which can then react with Nanoluciferase to produce a detectable bioluminescent signal. Bor-DTZ shows a dose-dependent response to hydrogen peroxide and selectivity over other biologically relevant reactive oxygen species and can be applied to detect either intra- or extracellular species. We further demonstrate the ability of this platform to monitor fluxes in extracellular hydrogen peroxide in a breast cancer cell line in response to the anticancer treatment, cisplatin.

A new synthesis of Schiff (K) 6 and Mannich bases (Q) 7 had formed compound (Q) 7 by reacting compound (K) with N-methylaniline at the presence of formalin 35% to given Mannich base (Q). Additionally, new complexes were formed by reacting Schiff base (K) with metal salts CuCl2·2H2O, PdCl2·2H2O, and PtCl6·6H2O by 2:1 of M:L ratio. New ligands and their complexes were characterized, exanimated, and confirmed through several techniques, including FTIR, UV-visible, 1H-NMR, 13C-NMR spectroscopy, CHN analysis, FAA, TG, molar conductivity, and magnetic susceptibility. These compounds and their complexes were screened against breast cancer cells. It was determined that several of these compounds had a significant anti-breast cancer effect due to their ability to induce cell death and reduce tumor growth. Metal complexes have been thoroughly studied as a potential anti-cancer therapy and have shown promising results. It was revealed these complexes uniquely affect the biological processes involved in cancer growth, leading to apoptosis and fading of cells. To form MCF-7 cell cultures, MCF-7 cells were seeded in 96-well plates at an appropriate density (5 × 105 cells/well). Metal complexes utilized in MCF-7 therapy have the potential to disband some of the harms associated with chemotherapy, such as drug resistance and toxicity.

Introduction. Rearrangement of molecular pathways and activation of bypass signaling determine the progression of tumor cell resistance to various drugs. Study of the common features of resistant formation mechanisms is essential for breast and other cancer beneficial treatments.Materials and methods. The present work was performed on estrogen receptor α ERα-positive (ERα – estrogen receptor α) McF-7 breast cancer cells, established sublines resistant to the mTOR inhibitor rapamycin or antiestrogen tamoxifen, and ERα-negative MDA-MB-231 breast cancer cells. Methods used include MTT test, transient transfection, immunoblotting, real-time polymerase chain reaction and methylation analysis by bisulfite pyrosequencing.Results. We have shown that the resistance of breast cancer cells to targeted and hormonal drugs is associated with the suppression of DNA methyltransferase 3A (DNMT3A) and respective changes in DNA methylation; DNMT3A knockdown results in the partial resistance to both drugs demonstrating the pivotal role of DNMT3A suppression in the progression of cell resistance.Conclusion. Totally, the results obtained highlight the possible mechanism of tumor cell resistance to targeting/hormonal drugs based on the deregulation of DNMTs expression and demonstrate direct connection between DNMT3A suppression and resistance progression.

BACKGROUND: Menopausal hormone therapy (MHT) is recommended for only five years to treat vasomotor symptoms and vulvovaginal atrophy because of safety concerns with long-term treatment. We investigated the ability of 2,3,4-trihydroxychalcone (2,3,4-THC) to modulate estrogen receptor (ER)-mediated responses in order to find drug candidates that could potentially prevent the adverse effects of long-term MHT treatment. METHODS: Transfection assays, real time-polymerase chain reaction, and microarrays were used to evaluate the effects of 2,3,4-THC on gene regulation. Radioligand binding studies were used to determine if 2,3,4-THC binds to ERα. Cell proliferation was examined in MCF-7 breast cancer cells by using growth curves and flow cytometry. Western blots were used to determine if 2,3,4-THC alters the E2 activation of the MAPK pathway and degradation of ERα. Chromatin immunoprecipitation was used to measure ERα binding to genes. RESULTS: The 2,3,4-THC/E2 combination produced a synergistic activation with ERα on reporter and endogenous genes in human U2OS osteosarcoma cells. Microarrays identified 824 genes that we termed reprogrammed genes because they were not regulated in U2OS-ERα cells unless they were treated with 2,3,4-THC and E2 at the same time. 2,3,4-THC blocked the proliferation of MCF-7 cells by preventing the E2-induced activation of MAPK and c-MYC transcription. The antiproliferative mechanism of 2,3,4-THC differs from selective estrogen receptor modulators (SERMs) because 2,3,4-THC did not bind to the E2 binding site in ERα like SERMs. CONCLUSION: Our study suggests that 2,3,4-THC may represent a new class of ERα modulators that do not act as a direct agonists or antagonists. We consider 2,3,4-THC to be a reprogramming compound, since it alters the activity of ERα on gene regulation and cell proliferation without competing with E2 for binding to ERα. The addition of a reprogramming drug to estrogens in MHT may offer a new strategy to overcome the adverse proliferative effects of estrogen in MHT by reprogramming ERα as opposed to an antagonist mechanism that involves blocking the binding of estrogen to ERα.

Etoposide is a chemotherapeutic medication used to treat various types of cancer, including breast cancer. It is established that pulsed electromagnetic field (PEMF) therapy can enhance the effects of anti-cancer chemotherapeutic agents. In this study, we investigated whether PEMFs influence the anti-cancer effects of etoposide in MCF-7 cells and determined the signal pathways affected by PEMFs. We observed that co-treatment with etoposide and PEMFs led to a decrease in viable cells compared with cells solely treated with etoposide. PEMFs elevated the etoposide- induced PARP cleavage and caspase-7/9 activation and enhanced the etoposide-induced down-regulation of survivin and up-regulation of Bax. PEMF also increased the etoposideinduced activation of DNA damage-related molecules. In addition, the reactive oxygen species (ROS) level was slightly elevated during etoposide treatment and significantly increased during co-treatment with etoposide and PEMF. Moreover, treatment with ROS scavenger restored the PEMF-induced decrease in cell viability in etoposide-treated MCF-7 cells. These results combined indicate that PEMFs enhance etoposide-induced cell death by increasing ROS induction-DNA damage-caspase-dependent apoptosis. [BMB Reports 2022; 55(3): 148-153].

Objective: The current study aimed to develop an experimental approach for the direct co-culture of three-dimensional breast cancer cells using single-cell RNA sequencing (scRNA-seq). Methods: The following four cell culture groups were established in the Matrigel matrix: the untreated Michigan Cancer Foundation (MCF)-7 cell culture group, the MCF-7 cell culture plus cisplatin group, the untreated co-culture group, and the cell co-culture plus cisplatin group. For cell co-culture, MCF-7 cells, human mammary fibroblasts, and human umbilical vein endothelial cells were mixed at a ratio of 1:1:1. Cisplatin was applied at a concentration of 1.25 μg/mL, and the cells were harvested after 2 days and subjected to scRNA-seq. Data were analyzed using a single-cell RNA sequencing data analysis pipeline with R language. Results: The response of MCF-7 cells to cisplatin differed among the four groups. The transcriptomic response of MCF-7 cells to cisplatin in the co-culture model was not as significant as that in the mono-culture model. Moreover, the pathways related to apoptosis, DNA damage, hypoxia, and metastasis in the co-culture groups were enriched in the genes that were differentially expressed based on cisplatin treatment. Conclusion: scRNA-seq analysis revealed that the response of MCF-7 cells to cisplatin in the co-culture model was lower than that in the mono-culture model. Therefore, the three-dimensional cell co-culture model can be applied to tumor research to better mimic the pathophysiological environment in vivo and can be a well-modified research method.