Search

The various therapeutic drugs that are currently utilized for the management of cancer, especially breast cancer, are greatly challenged by the augmented resistance that is either acquired or de novo by the cancer cells owing to the long treatment periods. So, this study aimed at elucidating the possible anticancer potential of four compounds 7, 4′, 7′′, 4′′′-tetra-O-methyl amentoflavone, hesperidin, ferulic acid, and chlorogenic acid that are isolated from Cycas thouarsii leaves n-butanol fraction for the first time. The MTT assay evaluated the cytotoxic action of four isolated compounds against MDA-MB-231 breast cancer cells and oral epithelial cells. Interestingly, ferulic acid revealed the lowest IC50 of 12.52 µg/mL against MDA-MB-231 cells and a high IC50 of 80.2 µg/mL against oral epithelial cells. Also, using an inverted microscope, the influence of ferulic acid was studied on the MDA-MB-231, which revealed the appearance of apoptosis characteristics like shrinkage of the cells and blebbing of the cell membrane. In addition, the flow cytometric analysis showed that the MDA-MB-231 cells stained with Annexin V/PI had a rise in the count of the cells in the early and late apoptosis stages. Moreover, gel electrophoresis detected DNA fragmentation in the ferulic acid-treated cells. Finally, the effect of the compound was tested at the molecular level by qRT-PCR. An upregulation of the pro-apoptotic genes (BAX and P53) and a downregulation of the anti-apoptotic gene (BCL-2) were observed. Consequently, our study demonstrated that these isolated compounds, especially ferulic acid, may be vital anticancer agents, particularly for breast cancer, through its induction of apoptosis through the P53-dependent pathway. [ABSTRACT FROM AUTHOR]

Background and aims. Adenomyosis is a heterogeneous disease, which differs from patient to patient. The objective of our study was to evaluate the risk factors that influence the occurrence of adenomyosis, more precisely to highlight aspects that may be used in practice. In addition, the in vitro impact of levonorgestrel (a possible predisposing factor in the occurrence of adenomyosis) on MDA-MB-231 cells was evaluated, trying to obtain a link between adenomyosis and mammary cancer. Methods. Clinical and demographic data of patients diagnosed with adenomyosis hospitalized between January and September 2023 in the Obstetrics-Gynecology Clinic were analyzed. For the in vitro assays, the MTT and LDH method was used to investigate the effect on cell viability and the potential cytotoxic effect of LG on MDA-MB-23 cells. Results. Out of a total of 99 hysterectomies performed, the diagnosis of adenomyosis was confirmed by ultrasound in 28 cases. Among our patients, we could observe that most of cases of adenomyosis developed in women between 40 and 45 years old. Multiple pregnancies can influence the development of this uterine pathology, along with a history of uterine surgery and abortions. It was also found that treatment with sex hormones can increase the risk of adenomyosis. Our in vitro study has showed that LG stimulates the proliferation of MDA-MB-231 cells depending on the dose and time. Conclusions. Personal history along with progestin treatment may influence myometrial lesions, leading to diffuse or focal adenomyosis. Moreover, in vitro, LG has been shown to stimulate the proliferation of breast cancer cells. [ABSTRACT FROM AUTHOR]

The various therapeutic drugs that are currently utilized for the management of cancer, especially breast cancer, are greatly challenged by the augmented resistance that is either acquired or de novo by the cancer cells owing to the long treatment periods. So, this study aimed at elucidating the possible anticancer potential of four compounds 7, 4′, 7′′, 4′′′-tetra-O-methyl amentoflavone, hesperidin, ferulic acid, and chlorogenic acid that are isolated from Cycas thouarsii leaves n-butanol fraction for the first time. The MTT assay evaluated the cytotoxic action of four isolated compounds against MDA-MB-231 breast cancer cells and oral epithelial cells. Interestingly, ferulic acid revealed the lowest IC50 of 12.52 µg/mL against MDA-MB-231 cells and a high IC50 of 80.2 µg/mL against oral epithelial cells. Also, using an inverted microscope, the influence of ferulic acid was studied on the MDA-MB-231, which revealed the appearance of apoptosis characteristics like shrinkage of the cells and blebbing of the cell membrane. In addition, the flow cytometric analysis showed that the MDA-MB-231 cells stained with Annexin V/PI had a rise in the count of the cells in the early and late apoptosis stages. Moreover, gel electrophoresis detected DNA fragmentation in the ferulic acid-treated cells. Finally, the effect of the compound was tested at the molecular level by qRT-PCR. An upregulation of the pro-apoptotic genes (BAX and P53) and a downregulation of the anti-apoptotic gene (BCL-2) were observed. Consequently, our study demonstrated that these isolated compounds, especially ferulic acid, may be vital anticancer agents, particularly for breast cancer, through its induction of apoptosis through the P53-dependent pathway.

Abstract A novel series of 2-cyano-3-(pyrazol-4-yl)-N-(thiazol-2-yl)acrylamide derivatives (3a–f) were synthesized using Knoevenagel condensation and characterized using various spectral tools. The weak nuclease activity of compounds (3a–f) against pBR322 plasmid DNA was greatly enhanced by irradiation at 365 nm. Compounds 3b and 3c, incorporating thienyl and pyridyl moieties, respectively, exhibited the utmost nuclease activity in degrading pBR322 plasmid DNA through singlet oxygen and superoxide free radicals’ species. Furthermore, compounds 3b and 3c affinities towards calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) were investigated using UV–Vis and fluorescence spectroscopic analysis. They revealed good binding characteristics towards CT-DNA with Kb values of 6.68 × 104 M−1 and 1.19 × 104 M−1 for 3b and 3c, respectively. In addition, compounds 3b and 3c ability to release free radicals on radiation were targeted to be used as cytotoxic compounds in vitro for colon (HCT116) and breast cancer (MDA-MB-231) cells. A significant reduction in the cell viability on illumination at 365 nm was observed, with IC50 values of 23 and 25 µM against HCT116 cells, and 30 and 9 µM against MDA-MB-231 cells for compounds 3b and 3c, respectively. In conclusion, compounds 3b and 3c exhibited remarkable DNA cleavage and cytotoxic activity on illumination at 365 nm which might be associated with free radicals’ production in addition to having a good affinity for interacting with CT-DNA and BSA. Graphical Abstract

A novel series of 2-cyano-3-(pyrazol-4-yl)-N-(thiazol-2-yl)acrylamide derivatives (3a–f) were synthesized using Knoevenagel condensation and characterized using various spectral tools. The weak nuclease activity of compounds (3a–f) against pBR322 plasmid DNA was greatly enhanced by irradiation at 365 nm. Compounds 3b and 3c, incorporating thienyl and pyridyl moieties, respectively, exhibited the utmost nuclease activity in degrading pBR322 plasmid DNA through singlet oxygen and superoxide free radicals' species. Furthermore, compounds 3b and 3c affinities towards calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) were investigated using UV–Vis and fluorescence spectroscopic analysis. They revealed good binding characteristics towards CT-DNA with Kb values of 6.68 × 104 M−1 and 1.19 × 104 M−1 for 3b and 3c, respectively. In addition, compounds 3b and 3c ability to release free radicals on radiation were targeted to be used as cytotoxic compounds in vitro for colon (HCT116) and breast cancer (MDA-MB-231) cells. A significant reduction in the cell viability on illumination at 365 nm was observed, with IC50 values of 23 and 25 µM against HCT116 cells, and 30 and 9 µM against MDA-MB-231 cells for compounds 3b and 3c, respectively. In conclusion, compounds 3b and 3c exhibited remarkable DNA cleavage and cytotoxic activity on illumination at 365 nm which might be associated with free radicals' production in addition to having a good affinity for interacting with CT-DNA and BSA. [ABSTRACT FROM AUTHOR]

In the present work, host and cerium-doped Zinc chromite nanoparticles (NPs) are synthesized by solution combustion method using Aloe Vera gel extract. The synthesized samples are characterized with different techniques. The Bragg reflections of ZnCr2O4:Ce (0–9 mol%) NPs confirms the formation of pure spinel cubic structure. The crystallite size, lattice strain, crystallinity, dislocation density were determined using Scherrer's and W–H plot method. The direct energy band gap was tuned from 3 to 2.8 eV. The direct energy band gap was found to decrease with increase in the dopant concentration. The cytotoxic properties of ZnCr2O4:Ce (0–9 mol%) NPs were tested against breast cancer cell (MDA-MB-231) and compared with that of Cisplatin, a standard drug. From the MTT assay, it is confirmed that the MDA-MB-231 cells are more sensitive to doped ZnCr2O4: Ce (1–9 mol%) NPs than the host matrix as well as with the standard drug Cisplatin. Compared to other dopant concentrations, the efficiency of ZnCr2O4: Ce (9 mol%) is more than that of the cisplatin and hence this can be used as the substitute for the cisplatin. [ABSTRACT FROM AUTHOR]

Abstract 2′,4′‐Dihydroxy‐6′‐methoxy‐3′,5′‐dimethylchalcone (DMC) is a typical and abundant chalcone compound from the buds of Cleistocalyx operculatus, which is well‐known for its edible and medicinal qualities. In this study, DMC showed effective cell cycle arrest at G2/M on MDA‐MB‐231 cells, though dual impacts, including the inhibition of microtubule polymerization through binding to β‐tubulin and the stimulation of reactive oxygen species (ROS) production by inhibiting catalase activity. The increased ROS level inhibited PI3K/Akt/mTOR pathway and further suppressed the expression level of Cdc2, Cdc25C, and Cyclin B1, alongside stimulated the expression level of p21 and p27. Above 29.5% MDA‐MB‐231 cells were arrested at G2/M phase, subsequently undergoing apoptosis due to heightened levels of apoptosis‐related proteins Bax and caspase 3. In summary, this study demonstrated that DMC concomitantly plays dual roles in apoptotic inducing by inhibiting the ROS consumption and microtubules formation in triple‐negative breast cancer cells.

AIM: To explore the effect and mechanism of the interfering Gal-1 on epithelial-mesenchymal transition (EMT), migration and proliferation in MDA-MB-231 cells via transforming growth factor-p (TGF-p) pathway. METHODS: The stable cell lines (shGal-1) which Gal-1 expression were inhibited completely and their control cell lines were used as experimental cells. Western blot assay was used to detect the effects of shGal-1 on EMT process of MDA-MB-231 cells after TGF-p treatment; The effect of shGal-1 on cell migration and invasion after TGF-p treatment was verified by cell scratch and transwell test; The effect of shGal-1 on the TGF-p pathway related proteins were detected by western blot; Finally, the effect of shGal-1 on cell proliferation was detected by MTT and western blot. RESULTS : shGal-1 inhibited TGF- p -mediated EMT in MDA-MB-231 cells and regulated phosphorylation of pathway signaling molecules (ERIK, AIKT and GSIK3p) ; shGal-1 could inhibit the proliferation of MDA-MB-231 cells. CONCLUSION: shGal-1 can inhibit the TGF-p-mediated EMT, migration and proliferation of MDA-MB-231 cells. [ABSTRACT FROM AUTHOR]

This work specifically examines the eco-friendly production of iron oxide nanoparticles from the red seaweed Hypnea valentiae (Hv-Fe 3 O 4 -NPs), with an emphasis on their potential applications in cancer treatment. The synthesised Hv-Fe 3 O 4 -NPs were characterised and confirmed through various analytical techniques such as UV–visible spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Energy-Dispersive X-ray Spectroscopy (EDS), X-Ray Diffraction analysis (XRD), Dynamic Light Scattering (DLS) and Vibrating Sample Magnetometry (VSM). Hv-Fe 3 O 4 -NPs exhibit notable DPPH and hydrogen peroxide scavenging abilities, suggesting their potential as antioxidants. Moreover, these nanoparticles exhibit effective anticancer efficacy against human MDA-MB-231 (breast cancer) cells (IC50 = 33.89 µg/mL) compared to lung cancer (A549 cells) (IC50 = 66.79 µg/mL). The Hv-Fe 3 O 4 -NPs effectively generates the reactive oxygen species (ROS) level to induce apoptotic activity in breast cancer cells. The RT-PCR gene expression analysis showed that Hv-Fe 3 O 4 -NPs could downregulate the expression of AKT and PI3K and upregulate the expression of PTEN at 34 µg/mL, showing strong anti-cancer activity. Moreover, the molecular docking examination of compounds from H. valentiae , which targeted the AKT/PI3K pathway proteins in breast carcinoma with aberrant mutations, resulted in advantageous binding scores. This research presents a sustainable and environmentally friendly approach with considerable potential for exhibiting antioxidant and anticancer properties, particularly against breast cancer. [Display omitted] • The red seaweed Hypnea valentiae is utilised to biologically synthesise Fe 3 O 4 -NPs. • The study emphasizes characterization and biological applications of Fe 3 O 4 -NPs. • Fe 3 O 4 -NPs demonstrated potent antioxidant activity by inhibiting free radicals. • The Fe 3 O 4 -NPs showed antitumor activity against human lung and breast cancer cells. • AKT/PI3K pathway regulates cell signalling, impacting cancer cell growth and survival. [ABSTRACT FROM AUTHOR]

2′,4′‐Dihydroxy‐6′‐methoxy‐3′,5′‐dimethylchalcone (DMC) is a typical and abundant chalcone compound from the buds of Cleistocalyx operculatus, which is well‐known for its edible and medicinal qualities. In this study, DMC showed effective cell cycle arrest at G2/M on MDA‐MB‐231 cells, though dual impacts, including the inhibition of microtubule polymerization through binding to β‐tubulin and the stimulation of reactive oxygen species (ROS) production by inhibiting catalase activity. The increased ROS level inhibited PI3K/Akt/mTOR pathway and further suppressed the expression level of Cdc2, Cdc25C, and Cyclin B1, alongside stimulated the expression level of p21 and p27. Above 29.5% MDA‐MB‐231 cells were arrested at G2/M phase, subsequently undergoing apoptosis due to heightened levels of apoptosis‐related proteins Bax and caspase 3. In summary, this study demonstrated that DMC concomitantly plays dual roles in apoptotic inducing by inhibiting the ROS consumption and microtubules formation in triple‐negative breast cancer cells. [ABSTRACT FROM AUTHOR]

(1) Background: The aim of the work is the evaluation of in vitro antiproliferative and pro-apoptotic activity of four benzimidazole derivatives containing colchicine-like and catechol-like moieties with methyl group substitution in the benzimidazole ring against highly invasive breast cancer cell line MDA-MB-231 and their related impairment of tubulin dynamics. (2) Methods: The antiproliferative activity was assessed with the MTT assay. Alterations in tubulin polymerization were evaluated with an in vitro tubulin polymerization assay and a docking analysis. (3) Results: All derivatives showed time-dependent cytotoxicity with IC50 varying from 40 to 60 μM after 48 h and between 13 and 20 μM after 72 h. Immunofluorescent and DAPI staining revealed the pro-apoptotic potential of benzimidazole derivatives and their effect on tubulin dynamics in living cells. Compound 5d prevented tubulin aggregation and blocked mitosis, highlighting the importance of the methyl group and the colchicine-like fragment. (4) Conclusions: The benzimidazole derivatives demonstrated moderate cytotoxicity towards MDA-MB-231 by retarding the initial phase of tubulin polymerization. The derivative 5d containing a colchicine-like moiety and methyl group substitution in the benzimidazole ring showed potential as an antiproliferative agent and microtubule destabilizer by facilitating faster microtubule aggregation and disrupting cellular and nuclear integrity. [ABSTRACT FROM AUTHOR]

AbstractIn recent years, metallic nanoparticles have attracted tremendous attention in nanomedicine. Here, we report green synthesis and determination of silver chloride nanoparticles synthesized using Artemisia sieberi extract (AgClNPs-ASE) and its anticancer properties against human breast cancer cells. Numerous techniques, such as X-ray diffraction (XRD), UV-visible spectra, transmission electron microscopy (TEM), scanning electron microscopy-energy dispersive spectra (SEM–EDS), and dynamic light scattering (DLS) analysis determined the morphology characteristics and size of the obtained nanoparticles. Cytotoxic properties of AgClNPs-ASE were carried out toward human breast cancer MDA-MB-231 cells and nontumorigenic HEK293 cells. AgClNPs-ASE revealed better efficacy toward breast cancer cells and was relatively less cytotoxic to nontumorigenic cells. Induction of apoptosis was further revealed by Hoechst 33258 dye and dual acridine orange and ethidium bromide (AO/EB) staining and in cells along with upregulation of caspase-8 and 9 proteins. AgClNPs-ASE could trigger the apoptosis by upregulation of early (1.93%) and late (58.86%) apoptosis followed by fluorescein isothiocyanate (FITC)‐Annexin‐V/PI staining and enhanced cell cycle population (sub-G1). AgClNPs-ASE significantly increased NO production in cancer cells. Moreover, qRT-PCR study showed that AgClNPs-ASE treated cells induce increased expression of the LncRNA GAS5 gene. These findings suggest the remarkable apoptosis in cancer cells triggered by AgClNPs-ASE in vitro. [ABSTRACT FROM AUTHOR]

Premna serratifolia Linn, a medicinally prominent plant is widely used in Ayruvedic, Siddha and Homeopathy medicinal treatments. In this study, out of its leaf fungal endophytes, about 68 Chaetomium sp. exhibited highest percentage similarity to the nearest genera (98.6 %) and thus were evaluated for its therapeutic properties. Chaetomium ethyl acetate extract contained flavonoids and phenolic compounds exhibited promising antioxidant activity against the 2,2-diphenyl-1-picrylhydrazyl radical. Chaetomium ethyl acetate extract induced cytotoxicity to MDA-MB-231, human breast cancer cells. Maximum cytotoxic activity and cell death was obtained with half maximal effective concentration of 96.82±5.23 µg upon exposure for 48 h. Apoptosis with chromatin condensation was visualized with acridine orange and propidium iodide dual staining at these conditions. It could stimulate cancerous MDA-MB-231 cells to undergo apoptosis (60.24 %) as evidenced by flow cytometer analysis mediated through elevated levels of reactive oxygen species (7.5 folds). Such excess reactive oxygen species generation resulted structural injury of the mitochondrial membrane its dissipation of membrane potential as identified by shift from red to green fluorescence of 5,5,6,6'-tetrachloro-1,1',3,3' tetraethylbenzimi-dazoylcarbocyanine iodide dye. One of the bioactive bestowing therapeutic potential was identified as chrysin, a flavone, by high performance liquid chromatography analysis of the extract against the standard chrysin (Rt, 24.68 min). Thus, an effective MDA-MB-231 apoptotic event by the extract is reported. [ABSTRACT FROM AUTHOR]

Rauvolfia tetraphylla is an essential medicinal plant that has been widely used in traditional medicine for various disease treatments. However, the tumor suppressor activity of R. tetraphylla and its phytocompounds were not explored against triple-negative breast cancer. The current research investigated the impact of R. tetraphylla methanolic extract (RTE) and its isolated compounds Ajmaline (RTC1) and Reserpine (RTC2) on triple-negative breast cancer cell line (MDA-MB-231) focusing on anti-proliferative effects. Our study imparts that RTE and RTC2 showed promising cytotoxic effects compared to RTC1. So further experiments have proceeded with RTE and RTC2, to evaluate its proliferation, migration, and apoptotic effect. The result shows around 80% of cells were observed in the G0/G1 phase in cell cycle analysis indicating the cell cycle inhibition and duel staining clearly showed the apoptotic effect. The migration of cells after the scratch was 60.45% observed in control and 90% in treated cells showing the inhibition of migration. ROS distribution was intense compared to control indicating the increased ROS stress in treated cells. Both RTE and RTC2-treated cells showed the potential to suppress proliferation and induce apoptotic change by upregulating BAX and MST-1 and suppressing Bcl2, LATS-1, and YAP, proving that deregulation of YAP resulting in the blockage of TEAD-YAP complex and inhibit proliferation. Therefore, R. tetraphylla extract and its isolated compounds were demonstrated to find its ability to act against MDA-MB-231 and these findings will help adjudicate it as a therapeutic drug against experimental triple-negative breast cancer. [ABSTRACT FROM AUTHOR]

Background: Breast Cancer continues to rank among all cancer types as the most dangerous malignancies, accounting for a significant portion of cancer-associated mortalities among women globally. Additionally, the number of breast cancer cases that are identified each year is rising globally. After surgery or radiation, the typical therapies entail chemotherapy which is followed by endocrine therapy. However, breast cancer is extremely resistant to therapies, which causes it to recur. As a result, emphasis is being placed on the development of complementary medicines with fewer adverse effects that are obtained from plants. An isoquinoline alkaloid, Protopine, possesses an array of biological properties, including anti-tumor efficacy against several malignancies. Materials and Methods: In this work, the anti-carcinogenic property of Protopine against the MDA-MB-231 cells has been investigated. The impact of Protopine on cell growth, apoptosis, ROS accumulation, and apoptotic marker levels was investigated. Doxorubicin was employed as the positive control drug in the studies. Results: The effect of Protopine on cell growth demonstrated its cytotoxic property was elevated dose-dependently and IC50 concentration was selected for additional work. The AO/EB and DAPI staining was performed to examine morphological alterations concerning apoptotic cell death. Additionally, Protopine augmented the ROS accumulation and induced DNA damage in Protopine-treated cells. The caspase levels were also increased upon Protopine treatment. Discussion and Conclusion: The outcomes highlight that Protopine remarkably inhibited cell growth by augmenting the ROS levels, inducing DNA fragmentation and apoptosis, leading to cell death by caspase-dependent pathway. Thus, Protopine could be possibly employed as an effective anti-cancer alternative for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Aim: Triple-negative breast cancer (TNBC) is a very aggressive subset of breast cancer, with limited treatment options, due to the lack of three commonly targeted receptors, which merits the need for novel treatments for TNBC. Towards this need, the use of metformin (Met), the most widely used type-2 diabetes drug worldwide, was explored as a repurposed anticancer agent. Cancer being a metabolic disease, the modulation of two crucial metabolites, glucose, and reactive oxygen species (ROS), is studied in MDA-MB-231 TNBC cells, using Met in the presence of electrical pulses (EP) to enhance the drug efficacy. Methods: MDA-MB-231, human TNBC cells were treated with Met in the presence of EP, with various concentrations Met of 1 mmol/L, 2.5 mmol/L, 5 mmol/L, and 10 mmol/L. EP of 500 V/cm, 800 V/cm, and 1,000 V/cm (with a pulse width of 100 µs at 1 s intervals) were applied to TNBC and the impact of these two treatments was studied. Various assays, including cell viability, microscopic inspection, glucose, ROS, and wound healing assay, were performed to characterize the response of the cells to the combination treatment. Results: Combining 1,000 V/cm with 5 mmol/L Met yielded cell viability as low as 42.6% at 24 h. The glucose level was reduced by 5.60-fold and the ROS levels were increased by 9.56-fold compared to the control, leading to apoptotic cell death. Conclusions: The results indicate the enhanced anticancer effect of Met in the presence of electric pulses. The cell growth is inhibited by suppressing glucose levels and elevated ROS. This shows a synergistic interplay between electroporation, Met, glucose, and ROS metabolic alterations. The results show promises for combinational therapy in TNBC patients.

Six previously unknown triterpene glycosides, pacificusosides L–Q (1–6), and two previously known triterpene glycosides, cucumariosides B1 (7) and A5 (8), were isolated from an alcoholic extract of Pacific sun star, Solaster pacificus. The structures of 1–6 were determined using 1D and 2D NMR, ESIMS, and chemical modifications. Compound 1 is a rare type of triterpene glycoside with non-holostane aglycon, having a linear trisaccharide carbohydrate chain. Pacificusosides M–P (2–5) have new structures containing a Δ8(9)-3,16,18-trihydroxy tetracyclic triterpene moiety. This tetracyclic fragment in sea star or sea cucumber triterpene glycosides was described for the first time. All the compounds under study exhibit low or moderate cytotoxic activity against colorectal carcinoma HCT 116 cells, and breast cancer MDA-MB-231 cells were assessed by MTS assay. Compound 2 effectively suppresses the colony formation of cancer cells at a non-toxic concentration, using the soft-agar assay. A scratch assay has shown a significant anti-invasive potential of compound 2 against HCT 116 cells, but not against MDA-MB-231 cells. [ABSTRACT FROM AUTHOR]

Certain insecticides are known to have estrogenic effects by activating estrogen receptors through genomic transcription. This has led researchers to associate specific insecticide use with an increased breast cancer risk. However, it is unclear if estrogen receptor-dependent pathways are the only way in which these compounds induce carcinogenic effects. The objective of this study was to determine the impact of the pyrethroid insecticide permethrin on the growth of estrogen receptor negative breast cancer cells MDA-MB-231. Using tandem mass spectrometric techniques, the effect of permethrin on cellular protein expression was investigated, and gene ontology and pathway function enrichment analyses were performed on the deregulated proteins. Finally, molecular docking simulations of permethrin with the candidate target protein was performed and the functionality of the protein was confirmed through gene knockdown experiments. Our findings demonstrate that exposure to 10–40 μM permethrin for 48 h enhanced cell proliferation and cell cycle progression in MDA-MB-231. We observed deregulated expression in 83 upregulated proteins and 34 downregulated proteins due to permethrin exposure. These deregulated proteins are primarily linked to transmembrane signaling and chemical carcinogenesis. Molecular docking simulations revealed that the overexpressed transmembrane signaling protein, G protein-coupled receptor 39 (GPR39), has the potential to bind to permethrin. Knockdown of GPR39 partially impeded permethrin-induced cellular proliferation and altered the expression of proliferation marker protein PCNA and cell cycle-associated protein cyclin D1 via the ERK1/2 signaling pathway. These findings offer novel evidence for permethrin as an environmental breast cancer risk factor, displaying its potential to impact breast cancer cell proliferation via an estrogen receptor-independent pathway.

Introduction/Justification: Breast cancer stands as the neoplasm group with the highest incidence rate among women worldwide. Laminin-111 a constituent of the tissue basement membrane, is implicated in the development of breast tumors. Biologically active peptides of laminin-111 such as YIGSR and IKVAV, play crucial roles in tumor growth, metastasis, protease secretion, and angiogenesis. These peptides exert significant influence on various aspects of cancer progression, emphasizing their potential as key targets for therapeutic intervention. Objectives: The aim of the study was to synthesize the bioactive peptides of laminin-111 (YIKVAV and YIGSR) and assess their interactions in triple-negative breast cancer cells. Materials and Methods: The YIKVAV and YIGSR peptides were synthesized through solid-phase peptide synthesis using the Fmoc/tBut strategy. Subsequently, the peptides underwent a characterization and purification process employing high performance liquid chromatography (HPLC) and mass spectrometry. The MDA-MB-231 breast tumor cell line was cultured in supplemented RPMI-1640 medium at 37°C and 5% CO2 until reaching 90% confluence. The growth curve of the MDA-MB-231 cell line was conducted in sextuplicate over a 7-day period, with cell counts performed on days 1, 3, 5, and 7. To assess the effect of peptides on cell proliferation, cells were seeded at a concentration of 2×104 in 6-well plates, with the inclusion of both YIKVAV and YIGSR peptides at 50 µM (n = 6). Cell viability in the presence of YIKVAV and YIGSR was determined using the MTT assay. For this analysis, cells were plated at a concentration of 2×104, with peptide concentration of 50 µM. Spectrophotometric analyses were realized after 24 h and 7 days of incubation at 595 nm. Results: The YIKVAV and YIGSR peptides were efficiently synthesized, yielding approximately 80% for both. Chromatographic analyzes conducted by HPLC and mass spectrometry confirmed the efficiency of the entire synthesis, cleavage, and characterization process of the peptides by the presence of only a single peak corresponding to the synthesized peptides. The growth curve profile determination of MDA-MB-231 cell line revealed exponential growth between days 5 and 7 of cell culture. The results indicate that the YIGSR peptide significantly inhibited cell growth by approximately 45%, whereas the YIKVAV fragment promoted cell growth by approximately 38% and (p < 0.0001) on the seventh day of cell culture. Regarding the MTT analysis after 24 h, no significant differences were observed between the control and treated groups for both fragments, suggesting that the peptides exhibited no toxicity at concentration of 50 µM. Additionally, on the 6th day, a reduction in tumor cell viability was observed for the YIGSR fragment, while an increase in viability was noted for YIKVAV (p < 0.0001). Conclusion: The YIKVAV and YIGSR peptides were effectively synthesized, characterized, and purified. The YIKVAV peptide, at a concentration of 50µM, promoted cell growth, while the YIGSR peptide significantly hindered the growth of the MDA-MB-231 cell line. This observation is consistent with the findings of cell viability assays conducted using MTT. This study holds significance for enhancing our comprehension of peptide actions in their interaction with triple-negative breast cancer cells, with the ultimate aim of proposing more effective targets for treatment.

Introduction: The inhibition of vascularization into tumor stroma as well as dynamic cell growth is the center of attention. Here, we aimed to examine the role of vandetanib on angiogenesis capacity of breast cancer stem cell (CSCs). Methods: MDA-MB-231 cells were exposed to different doses of vandetanib and survival rate was monitored. Stimulatory effects of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and epidermal growth factor (EGF) were evaluated in vandetanib-treated MDA-MB-231 cells. In vitro tubulogenesis capacity was studied on the Matrigel surface. The synergistic effects of vandetanib on cell survival were also assessed after PI3K and/or Wnt3a inhibition. Vascular endothelial (VE)-cadherin, matrix metalloproteinase-2 (MMP-2), -9, Wnt3a, and p-Akt/Akt ratio were measured using western blotting. Results: Vandetanib reduced survival rate in a dose-dependent manner (P

Objective(s): Encapsulation of essential oil in polymeric nanoparticles (NPs) increases their retention and improves their efficacy. Here, eucalyptus essential oil (EEO) encapsulate in the chitosan (CS) NPs increases its retention, and enhances the anticancer effect of EEO.Materials and Methods: The effects of pH, chitosan sodium tripolyphosphate ratio, and chitosan concentration on the size and charge NPs were evaluated. The success of EEO encapsulation was confirmed by FT-IR, UV–Vis spectroscopy, and GC techniques. The toxic effect of free EEO and CS-EEO NPs was investigated in MDA-MB-231 breast cancer cells and fibroblast normal cells. Results: The optimized obtained EEO -loaded chitosan nanoparticles (CS-EEO NPs) were spherical with an average diameter of 86 nm, a polydispersity index below 0.4, and positive zeta potential (+14.25 mV) as confirmed. Increasing the concentration and pH of the chitosan solution and decreasing the chitosan/sodium tripolyphosphate ratio, the size of NPs decreased. Loading capacity (LC) and encapsulation efficiency (EE) of EEO in the NPs were about 45% and 32–76%, respectively. The chitosan nanoparticles exhibited a biphasic release profile with the release of 87% of the EEO in the first 5 h, followed by a sustained release for the next 43 h. Conclusion: The free EEO was more toxic for MDA-MB-231 cells than fibroblast cells; however, CS-EEO NPs were non-toxic for fibroblast cells and more toxic for MDA-MB-231 cells compared to free EEO. Therefore, the CS-EEO NPs illustrate smart behavior in killing cancerous cells and will be suggested for breast cancer drug delivery.

A total of 28 derivatives were designed and synthesized, including 18 estradiol-amino acid (17β-OH) derivatives (I-2 ∼ I-19) and 10 estradiol-amino acid (16-C) derivatives (II-2 ∼ II-11). Amino acids used in synthesis include L-phenylalanine, L-serine, L-leucine, glycine, L-proline and L-glutamine. The results showed that I-8 ∼ I-12 of 17β-OH conjugated amino acids in 17β-estradiol had good in vitro antitumor activity, indicating that the introduction of amino acids could improve the anti-proliferative effect. Among them, 3-benzyloxy-Estra-1,3,5 (10)-triene-17β-ol pyrrolidine-2-carboxylate hydrochloride (I-12) showed the best inhibitory activity against breast cancer (MDA-MB-231) cells (IC50 = 4.89 µM). Further studies on apoptosis revealed that I-12 could regulate the expression of apoptosis-related proteins in MDA-MB-231 cells. Network pharmacology and molecular docking analysis revealed that I-12 may act on targets such as mechanistic target of rapamycin kinase (mTOR), estrogen receptor 1 (ESR1), pyruvate dehydrogenase kinase (PDK2) targets and their related pathways.

Objective: To examine the impact of ginger volatile oil (GVO) on the growth of MDA-MB-231 breast cancer cells in the presence of bisphenol A (BPA) by modulating the diversity of gut microbiota. Methods: MDA-MB-231 breast cancer cells were injected subcutaneously into the right armpit of female BALB/c Nude (nu/nu) mice to create a triple negative breast cancer model. Thirty nude mice were randomly divided into 5 groups: control group (distilled water every day), BPA control group (distilled PEG-400+ DMSO + cyclodextrin every day), BPA + GVO (0.25 mL/kg) group, BPA + GVO (0.5 mL/kg) group, BPA + GVO (1 mL/kg) group, 6 mice in each group; The drug was given by gavage once a day for 4 weeks. At the end of the experiment, the changes of tumor mass and tumor volume were observed and compared in 5 groups of tumor-bearing mice. High-throughput sequencing (16S rRNA) was used to detect the changes of gut microflora in each group. Results: The volume and weight of breast cancer decreased in the low, medium and high dose groups of GVO. Among them, the difference between the high-dose group and the BPA group reached a significant level (P

Silver nanoparticles (AgNPs) have become a research focus due to its antimicrobial, anticancer applications and cost-effective properties. In this study the effectiveness of green synthesis of NPs using biological macromolecule chitosan which is acting as a reducing cum stabilizing agent is carried out. An in-depth analysis of the synthesized AgNPs was conducted using a variety of sophisticated characterization techniques such as UV-visible spectroscopy, particle size analysis, zeta potential measurements, transmission electron microscopy (TEM), photoluminescence, and Fourier transform infrared (FTIR) spectroscopy. The antimicrobial activity of the formulated AgNPs were inspected against two human pathogenic strains. In the antimicrobial activity, the synthesized AgNPs exhibited a reduction in the growth of both the microbes. The minimum inhibitory concentration (MIC) of 1.22 휇M was observed for both Candida albicans and Mycobacterium smegmatis. Consequently, AgNPs may be used as an opportunity for modern-day antibiotics to treat infections due to human pathogens. Antiproliferative analysis revealed that AgNPs showed antiproliferative characteristics against MDA-MB-231 cells compared to the control. Such AgNPs have an anticancer effect and are likely to be used as smart drug delivery mediators to treat late-stage cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: The burden of breast cancer has been increasing at an alarming rate. Epidemiological and empirical evidence has shown the key roles of vitamin D in the mitigation of tumor burden. But, the mechanisms by which vitamin D induces tumor reduction are poorly understood. Therefore, in the current study, we have aimed at understanding the role of vitamin D in inhibiting breast cancer progression in in vitro and in vivo models. The results of this study showed that vitamin D inhibited the proliferation of breast cancer cell lines in vitro and retarded Ehrlich ascites carcinomas in mice by inducing apoptosis as well as by halting cell cycle progression and angiogenesis. Future studies should focus more on strategies to improve the therapeutic index and the retention of vitamin D in tumor cells for better and long-lasting treatment. The incidence of aggressive and resistant breast cancers is growing at alarming rates, indicating a necessity to develop better treatment strategies. Recent epidemiological and preclinical studies detected low serum levels of vitamin D in cancer patients, suggesting that vitamin D may be effective in mitigating the cancer burden. However, the molecular mechanisms of vitamin D3 (cholecalciferol, vit-D3)-induced cancer cell death are not fully elucidated. The vit-D3 efficacy of cell death activation was assessed using breast carcinoma cell lines in vitro and a widely used Ehrlich ascites carcinoma (EAC) breast cancer model in vivo in Swiss albino mice. Both estrogen receptor-positive (ER+, MCF-7) and -negative (ER-, MDA-MB-231, and MDA-MB-468) cell lines absorbed about 50% of vit-D3 in vitro over 48 h of incubation. The absorbed vit-D3 retarded the breast cancer cell proliferation in a dose-dependent manner with IC50 values ranging from 0.10 to 0.35 mM. Prolonged treatment (up to 72 h) did not enhance vit-D3 anti-proliferative efficacy. Vit-D3-induced cell growth arrest was mediated by the upregulation of p53 and the downregulation of cyclin-D1 and Bcl2 expression levels. Vit-D3 retarded cell migration and inhibited blood vessel growth in vitro as well as in a chorioallantoic membrane (CAM) assay. The intraperitoneal administration of vit-D3 inhibited solid tumor growth and reduced body weight gain, as assessed in mice using a liquid tumor model. In summary, vit-D3 cytotoxic effects in breast cancer cell lines in vitro and an EAC model in vivo were associated with growth inhibition, the induction of apoptosis, cell cycle arrest, and the impediment of angiogenic processes. The generated data warrant further studies on vit-D3 anti-cancer therapeutic applications. [ABSTRACT FROM AUTHOR]

(1) Background: The aim of the work is the evaluation of in vitro antiproliferative and pro-apoptotic activity of four benzimidazole derivatives containing colchicine-like and catechol-like moieties with methyl group substitution in the benzimidazole ring against highly invasive breast cancer cell line MDA-MB-231 and their related impairment of tubulin dynamics. (2) Methods: The antiproliferative activity was assessed with the MTT assay. Alterations in tubulin polymerization were evaluated with an in vitro tubulin polymerization assay and a docking analysis. (3) Results: All derivatives showed time-dependent cytotoxicity with IC50 varying from 40 to 60 μM after 48 h and between 13 and 20 μM after 72 h. Immunofluorescent and DAPI staining revealed the pro-apoptotic potential of benzimidazole derivatives and their effect on tubulin dynamics in living cells. Compound 5d prevented tubulin aggregation and blocked mitosis, highlighting the importance of the methyl group and the colchicine-like fragment. (4) Conclusions: The benzimidazole derivatives demonstrated moderate cytotoxicity towards MDA-MB-231 by retarding the initial phase of tubulin polymerization. The derivative 5d containing a colchicine-like moiety and methyl group substitution in the benzimidazole ring showed potential as an antiproliferative agent and microtubule destabilizer by facilitating faster microtubule aggregation and disrupting cellular and nuclear integrity.

Vasculogenic mimicry (VM) is an intriguing phenomenon observed in tumor masses, in which cancer cells organize themselves into capillary-like channels that closely resemble the structure and function of blood vessels. Although VM is believed to contribute to alternative tumor vascularization, the detailed regulatory mechanisms controlling these cellular processes remain poorly understood. Our study aimed to investigate the role of Early Growth Response 1 (EGR1) in regulating VM in aggressive cancer cells, specifically MDA-MB-231 triple-negative breast cancer cells. Our study revealed that EGR1 promotes the formation of capillary-like tubes by MDA-MB-231 cells in a 3-dimensional Matrigel matrix. EGR1 was observed to upregulate Kruppel-like factor 4 (KLF4) expression, which regulates the formation of the capillary-like tube structure. Additionally, our findings highlight the involvement of the ERK1/2 and p38 mitogen-activated protein kinase pathways in mediating the expression of EGR1 and KLF4, underscoring their crucial role in VM in MDA-MB-231 cells. Understanding these regulatory mechanisms will provide valuable insights into potential therapeutic targets for preventing VM during the treatment of triple-negative breast cancer. [ABSTRACT FROM AUTHOR]

Introduction: The inhibition of vascularization into tumor stroma as well as dynamic cell growth is the center of attention. Here, we aimed to examine the role of vandetanib on angiogenesis capacity of breast cancer stem cell (CSCs). Methods: MDA-MB-231 cells were exposed to different doses of vandetanib and survival rate was monitored. Stimulatory effects of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and epidermal growth factor (EGF) were evaluated in vandetanibtreated MDA-MB-231 cells. In vitro tubulogenesis capacity was studied on the Matrigel surface. The synergistic effects of vandetanib on cell survival were also assessed after PI3K and/or Wnt3a inhibition. Vascular endothelial (VE)-cadherin, matrix metalloproteinase-2 (MMP-2), -9, Wnt3a, and p-Akt/Akt ratio were measured using western blotting. Results: Vandetanib reduced survival rate in a dose-dependent manner (P < 0.05). Proliferative effects associated with VEGF, FGF, and EGF were blunted in these cells pre-exposed to vandetanib (P < 0.05). The microcirculation pattern's triple-negative breast cancer (TNBC) was suppressed by 1, 5 µM of vandetanib (P < 0.05). Hence 1, 5 µM of vandetanib potentially decreased the population of CD24-cells. 1 and 5 µM of vandetanib inhibited cell proliferation by blocking PI3K and Wnt3a pathways and decreased the p-Akt/Akt ratio, Wnta3 protein levels (P < 0.05). 1 and 5 µM vandetanib combined with PI3K inhibitor diminished metastatic markers including, MMP-2, and MMP-9. The concurrent treatment (PI3K, inhibitor+ 1, 5 µM vandetanib) also considerably reduced epithelial-mesenchymal transition (EMT) markers such as VE-cadherin (P < 0.05). Conclusion: Vandetanib suppressed vasculogenic mimicry (VM) networking through blunting stemness properties, coincided with suppression of VE-cadherin in CSCs. [ABSTRACT FROM AUTHOR]

Thymol has antioxidant, apoptotic, anti-cancer and, anti-inflammatory properties. In this study iron oxide nanoparticles were synthetized by chemical co-precipitation method, then coated with albumin and finally loaded with thymol. The properties and characteristics of these composites were investigated by x-ray diffraction (XRD), TEM, FTIR, FE-SEM, DLS, zeta potential techniques and, vibrating-sample magnetometry (VSM). Finally, the release and encapsulation behavior of these compounds was calculated. The anti-cancer effect of thymol loaded albumin-coated Fe3O4 nanoparticles were investigated by the MTT method. The rate of apoptosis was assessed by Flow Cytometry test, while BAX and BCL2 were assessed by ELISA test. Expression of the MAP1LC3A gene was also examined by the real-time PCR technique. The results of MTT, ELISA, Flow Cytometry, and, real-time PCR techniques showed that thymol loaded albumin-coated Fe3O4 nanoparticles at concentration of 150 μg/mL for 72-hour treatment most significantly affected cytotoxicity, apoptosis and, autophagy. Hence, this compound probably exhibited anti-cancer effect on the MDA-MB-231 cell line by activating the autophagy and apoptosis pathways. [ABSTRACT FROM AUTHOR]

Objective(s): Encapsulation of essential oil in polymeric nanoparticles (NPs) increases their retention and improves their efficacy. Here, eucalyptus essential oil (EEO) encapsulate in the chitosan (CS) NPs increases its retention, and enhances the anticancer effect of EEO. Materials and Methods: The effects of pH, chitosan sodium tripolyphosphate ratio, and chitosan concentration on the size and charge NPs were evaluated. The success of EEO encapsulation was confirmed by FT-IR, UV-Vis spectroscopy, and GC techniques. The toxic effect of free EEO and CS-EEO NPs was investigated in MDA-MB-231 breast cancer cells and fibroblast normal cells. Results: The optimized obtained EEO -loaded chitosan nanoparticles (CS-EEO NPs) were spherical with an average diameter of 86 nm, a polydispersity index below 0.4, and positive zeta potential (+14.25 mV) as confirmed. Increasing the concentration and pH of the chitosan solution and decreasing the chitosan/sodium tripolyphosphate ratio, the size of NPs decreased. Loading capacity (LC) and encapsulation efficiency (EE) of EEO in the NPs were about 45% and 32-76%, respectively. The chitosan nanoparticles exhibited a biphasic release profile with the release of 87% of the EEO in the first 5 h, followed by a sustained release for the next 43 h. Conclusion: The free EEO was more toxic for MDA-MB-231 cells than fibroblast cells; however, CS-EEO NPs were non-toxic for fibroblast cells and more toxic for MDA-MB-231 cells compared to free EEO. Therefore, the CS-EEO NPs illustrate smart behavior in killing cancerous cells and will be suggested for breast cancer drug delivery. [ABSTRACT FROM AUTHOR]

Quercetin (QRC), a flavonoid found in foods and plants such as red wine, onions, green tea, apples, and berries, possesses remarkable anti-inflammatory and antioxidant properties. These properties make it effective in combating cancer cells, reducing inflammation, protecting against heart disease, and regulating blood sugar levels. To enhance the potential of inclusion complexes (ICs) containing β-cyclodextrin (β-CD) in cancer therapy, they were transformed into nano-inclusion complexes (NICs). In this research, NICs were synthesized using ethanol as a reducing agent in the nanoprecipitation process. By employing FT-IR analysis, it was observed that hydrogen bonds were formed between QRC and β-CD. Moreover, the IC molecules formed NICs through the aggregation facilitated by intermolecular hydrogen bonds. Proton NMR results further confirmed the occurrence of proton shielding and deshielding subsequent to the formation of NICs. The introduction of β-CDs led to the development of a distinctive feather-like structure within the NICs. The particle sizes were consistently measured around 200 nm, and both SAED and XRD patterns indicated the absence of crystalline NICs, providing supporting evidence. Through cytotoxicity and fluorescence-assisted cell-sorting analysis, the synthesized NICs showed no significant damage in the cell line of MCF-7. In comparison to QRC alone, the presence of high concentrations of NICs exhibited a lesser degree of toxicity in normal human lung fibroblast MRC-5 cells. Moreover, the individual and combined administration of both low and high concentrations of NICs effectively suppressed the growth of cancer cells (MDA-MB-231). The solubility improvement resulting from the formation of QRC-NICs with β-CD enhanced the percentage of cell survival for MCF-7 cell types. [ABSTRACT FROM AUTHOR]

Aim: Triple negative breast cancer (TNBC) is difficult to treat since it lacks all the three most commonly targeted hormone receptors. Patients afflicted with TNBC are treated with platinum core chemotherapeutics, such as cisplatin. Despite the initial effective anticancer effects of cisplatin, TNBC attenuates its effect and develops resistance eventually, which results in tumor reoccurrence. Hence, there is a critical demand for effective, alternative, and natural ways to treat TNBC. Towards this, a promising technique for inhibiting TNBC cell proliferation involves promoting the production of reactive oxygen species (ROS), which triggers pro-apoptotic caspases 9 and 3. Resveratrol (RESV), an active bio compound found in naturally available fruits, such as grapes, is utilized in this research for that. In addition, electrochemotherapy (ECT), which involves the application of electrical pulses (EP), was utilized to enhance the uptake of RESV. Methods: MDA-MB-231, human TNBC cells were treated with/out RESV, and eight 600–1,000 V/cm, 100 μs pulses at 1 Hz. The cells were characterized by using various assays, including viability assay, and ROS assay. Results: A TNBC cell viability of as low as 20% was obtained at 24 h (it was 13% at 60 h), demonstrating the potential of this novel treatment. ROS production was the highest in the combination of EP at 1,000 V/cm along with RESV at 100 μmol/L. Conclusions: Results indicate that RESV has the potential as an anti-TNBC agent and that EP + RESV can significantly enhance the cell death to reduce MDA-MB-231 cell viability by increasing ROS production and triggering apoptosis.

Abstract Background Preclinical evidence from us and others demonstrates that the anticancer effects of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors can be enhanced with focal radiation therapy (RT), but only when RT is delivered prior to (rather than after) CDK4/6 inhibition. Depending on tumor model, cellular senescence (an irreversible proliferative arrest that is associated with the secretion of numerous bioactive factors) has been attributed beneficial or detrimental effects on response to treatment. As both RT and CDK4/6 inhibitors elicit cellular senescence, we hypothesized that a differential accumulation of senescent cells in the tumor microenvironment could explain such an observation, i.e., the inferiority of CDK4/6 inhibition with palbociclib (P) followed by RT (P→RT) as compared to RT followed by palbociclib (RT→P). Methods The impact of cellular senescence on the interaction between RT and P was assessed by harnessing female INK-ATTAC mice, which express a dimerizable form of caspase 8 (CASP8) under the promoter of cyclin dependent kinase inhibitor 2A (Cdkn2a, coding for p16Ink4), as host for endogenous mammary tumors induced by the subcutaneous implantation of medroxyprogesterone acetate (MPA, M) pellets combined with the subsequent oral administration of 7,12-dimethylbenz[a]anthracene (DMBA, D). This endogenous mouse model of HR+ mammary carcinogenesis recapitulates key immunobiological aspects of human HR+ breast cancer. Mice bearing M/D-driven tumors were allocated to RT, P or their combination in the optional presence of the CASP8 dimerizer AP20187, and monitored for tumor growth, progression-free survival and overall survival. In parallel, induction of senescence in vitro, in cultured human mammary hormone receptor (HR)+ adenocarcinoma MCF7 cells, triple negative breast carcinoma MDA-MB-231 cells and mouse HR+ mammary carcinoma TS/A cells treated with RT, P or their combination, was determined by colorimetric assessment of senescence-associated β-galactosidase activity after 3 or 7 days of treatment. Results In vivo depletion of p16Ink4-expressing (senescent) cells ameliorated the efficacy of P→RT (but not that of RT→P) in the M/D-driven model of HR+ mammary carcinogenesis. Accordingly, P→RT induced higher levels of cellular senescence than R→TP in cultured human and mouse breast cancer cell lines. Conclusions Pending validation in other experimental systems, these findings suggest that a program of cellular senescence in malignant cells may explain (at least partially) the inferiority of P→RT versus RT→P in preclinical models of HR+ breast cancer.

Fisetin (FS) is considered a safer phytomedicine alternative to conventional chemotherapeutics for breast cancer treatment. Despite its surpassing therapeutic potential, its clinical utility is hampered by its low systemic bioavailability. Accordingly, as far as we are aware, this is the first study to develop lactoferrin-coated FS-loaded β-cyclodextrin nanosponges (LF-FS-NS) for targeted FS delivery to breast cancer. NS formation through cross-linking of β-cyclodextrin by diphenyl carbonate was confirmed by FTIR and XRD. The selected LF-FS-NS showed good colloidal properties (size 52.7 ± 7.2 nm, PDI < 0.3, and ζ-potential 24 mV), high loading efficiency (96 ± 0.3%), and sustained drug release of 26 % after 24 h. Morphological examination using SEM revealed the mesoporous spherical structure of the prepared nanosponges with a pore diameter of ~30 nm, which was further confirmed by surface area measurement. Additionally, LF-FS-NS enhanced FS oral and IP bioavailability (2.5- and 3.2-fold, respectively) compared to FS suspension in rats. Antitumor efficacy evaluation in vitro on MDA-MB-231 cells and in vivo on an Ehrlich ascites mouse model demonstrated significantly higher activity and targetability of LF-FS-NS (30 mg/kg) compared to the free drug and uncoated formulation. Consequently, LF-FS-NS could be addressed as a promising formulation for the effective management of breast cancer. [ABSTRACT FROM AUTHOR]

Objective(s): Breast cancer cells developing radioresistance during radiation may result in cancer recurrence and poor survival. One of the main reasons for this problem is the changes in the regulation of genes that have a key role in the epithelial-mesenchymal transition (EMT). Utilizing mesenchymal stem cells can be an effective approach to overcome therapeutic resistance. In this study, we investigated the possibility of combining mesenchymal medium with cancer cell medium in sensitizing breast carcinoma cells to radiation. Materials and Methods: In this experimental study, the cells were irradiated at a dose of 4 Gy alone and in combination with stem cells and cancer cells media. Apoptosis, cell cycle, Western blotting, and real-time PCR assays evaluated the therapeutic effects. Results: We found that the CSCM could decrease the expression of several EMT markers (CD133, CD44, Vimentin, Nanog, Snail, and Twist), resulting in increased cell distribution in the G1 and G2/M phases, apoptosis rate, and protein levels of p-Chk2 and cyclin D1; furthermore, it exhibits synergetic effects with radiation treatment in vitro. Conclusion: These findings show that CSCM inhibits the expansion of breast cancer cells and makes them more susceptible to radiotherapy, offering a unique approach to treating breast cancer by overcoming radioresistance. [ABSTRACT FROM AUTHOR]

Abstract Tumor acidosis, a common phenomenon in solid cancers such as breast cancer, is caused by the abnormal metabolism of cancer cells. The low pH affects cells surrounding the cancer, and tumor acidosis has been shown to inhibit the activity of immune cells. Despite many previous studies, the immune surveillance mechanisms are not fully understood. We found that the expression of PD-L1 was significantly increased under conditions of extracellular acidosis in MDA-MB-231 cells. We also confirmed that the increased expression of PD-L1 mediated by extracellular acidosis was decreased when the pH was raised to the normal range. Gene set enrichment analysis (GSEA) of public breast cancer patient databases showed that PD-L1 expression was also highly correlated with IL-6/JAK/STAT3 signaling. Surprisingly, the expression of both phospho-tyrosine STAT3 and PD-L1 was significantly increased under conditions of extracellular acidosis, and inhibition of STAT3 did not increase the expression of PD-L1 even under acidic conditions in MDA-MB-231 cells. Based on these results, we suggest that the expression of PD-L1 is increased by tumor acidosis via activation of STAT3 in MDA-MB-231 cells.

Background: Preclinical evidence from us and others demonstrates that the anticancer effects of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors can be enhanced with focal radiation therapy (RT), but only when RT is delivered prior to (rather than after) CDK4/6 inhibition. Depending on tumor model, cellular senescence (an irreversible proliferative arrest that is associated with the secretion of numerous bioactive factors) has been attributed beneficial or detrimental effects on response to treatment. As both RT and CDK4/6 inhibitors elicit cellular senescence, we hypothesized that a differential accumulation of senescent cells in the tumor microenvironment could explain such an observation, i.e., the inferiority of CDK4/6 inhibition with palbociclib (P) followed by RT (P→RT) as compared to RT followed by palbociclib (RT→P). Methods: The impact of cellular senescence on the interaction between RT and P was assessed by harnessing female INK-ATTAC mice, which express a dimerizable form of caspase 8 (CASP8) under the promoter of cyclin dependent kinase inhibitor 2A (Cdkn2a, coding for p16Ink4), as host for endogenous mammary tumors induced by the subcutaneous implantation of medroxyprogesterone acetate (MPA, M) pellets combined with the subsequent oral administration of 7,12-dimethylbenz[a]anthracene (DMBA, D). This endogenous mouse model of HR+ mammary carcinogenesis recapitulates key immunobiological aspects of human HR+ breast cancer. Mice bearing M/D-driven tumors were allocated to RT, P or their combination in the optional presence of the CASP8 dimerizer AP20187, and monitored for tumor growth, progression-free survival and overall survival. In parallel, induction of senescence in vitro, in cultured human mammary hormone receptor (HR)+ adenocarcinoma MCF7 cells, triple negative breast carcinoma MDA-MB-231 cells and mouse HR+ mammary carcinoma TS/A cells treated with RT, P or their combination, was determined by colorimetric assessment of senescence-associated β-galactosidase activity after 3 or 7 days of treatment. Results: In vivo depletion of p16Ink4-expressing (senescent) cells ameliorated the efficacy of P→RT (but not that of RT→P) in the M/D-driven model of HR+ mammary carcinogenesis. Accordingly, P→RT induced higher levels of cellular senescence than R→TP in cultured human and mouse breast cancer cell lines. Conclusions: Pending validation in other experimental systems, these findings suggest that a program of cellular senescence in malignant cells may explain (at least partially) the inferiority of P→RT versus RT→P in preclinical models of HR+ breast cancer. [ABSTRACT FROM AUTHOR]

Breast cancer is the most commonly diagnosed cancer and a leading cause of cancer-related death among women worldwide. Somatostatin (SST) and Cannabinoids have an anti-proliferative and pro-apoptotic effect, but the mechanisms of their actions remain elusive. In the present study, we have evaluated the effects of SST, Cannabidiol (CBD) alone or in combination on receptor expression, cell proliferation and apoptosis and related downstream signalling pathways in MDA-MB-231 and MCF-7 breast cancer cells. The results presented here demonstrate the cell type and agonist-dependent changes in receptor expression at the cell membrane, inhibition of cell proliferation and increased apoptosis following treatment with SST and CBD alone and in combination. In comparison to MDA-MB-231 cells, MCF-7 cells treated with SST alone and in combination with CBD exhibited inhibition of phosphorylated Protein Kinase B (pAKT) and phosphorylated-Phosphoinositide 3-Kinase (pPI3K) expression. Importantly, inhibition of PI3K/AKT activation was accompanied by enhanced PTEN expression in MCF-7 cells. These results highlight the possible interaction between SSTR and CBR subtypes with the implication in the modulation of receptor expression, cell viability and signal transduction pathways in a breast cancer cell type-dependent manner. • Breast cancer is the leading cause of cancer-related death among women worldwide. • Somatostatin and Cannabinoids displayed an anti-proliferative and pro-apoptotic effect in the cancer cell lines. • SST with or without CBD exhibited inhibition of signalling pathways associated with cell proliferation. • Our results indicate the possibility of SSTRs and CBRs crosstalk as novel therapeutic target in breast cancer treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: This work intends to unravel one of the roles played by transglutaminase 2 within the cell. We highlighted its physical interaction with the voltage-dependent Kv10.1 K+ channel, an important target of therapies in breast cancer. The use of transglutaminase 2 inhibitors can selectively affect the membrane current of triple-negative cells in which this channel is functional. Since the multifunctionality of transglutaminase 2 (TG2) includes extra- and intracellular functions, we investigated the effects of intracellular administration of TG2 inhibitors in three breast cancer cell lines, MDA-MB-231, MDA-MB-436 and MDA-MB-468, which are representative of different triple-negative phenotypes, using a patch-clamp technique. The first cell line has a highly voltage-dependent a membrane current, which is low in the second and almost absent in the third one. While applying a voltage protocol to responsive single cells, injection of TG2 inhibitors triggered a significant decrease of the current in MDA-MB-231 that we attributed to voltage-dependent K+ channels using the specific inhibitors 4-aminopyridine and astemizole. Since the Kv10.1 channel plays a dominant role as a marker of cell migration and survival in breast cancer, we investigated its relationship with TG2 by immunoprecipitation. Our data reveal their physical interaction affects membrane currents in MDA-MB-231 but not in the less sensitive MDA-MB-436 cells. We further correlated the efficacy of TG2 inhibition with metabolic changes in the supernatants of treated cells, resulting in increased concentration of methyl- and dimethylamines, representing possible response markers. In conclusion, our findings highlight the interference of TG2 inhibitors with the Kv10.1 channel as a potential therapeutic tool depending on the specific features of cancer cells. [ABSTRACT FROM AUTHOR]

The great potential of zinc oxide nanoparticles (ZnO NPs) for biomedical applications is attributed to their physicochemical properties. In this work, pure and Ag and Ce dual-doped ZnO NPs were synthesized through a facile and green route to examine their cytotoxicity in breast cancer and normal cells. The initial preparation of dual-doped nanoparticles was completed by the usage of taranjabin. The synthesis of Ag and Ce dual-doped ZnO NPs was started with preparing the Ce:Ag ratios of 1:1, 1:2, and 1:4. The cytotoxicity effects of synthesized nanoparticles against breast normal cells (MCF-10A) and breast cancer cells (MDA-MB-231) were examined. The hexagonal structure of synthesized nanoparticles was observed through the results of X-ray diffraction (XRD). Scanning electron microscopy (SEM) images exhibited the spherical shape and smooth surfaces of prepared particles along with the homogeneous distribution of Ag and Ce in ZnO with high-quality lattice fringes without any distortions. According to the cytotoxic results, the effects of Ag/Ce dual-doped ZnO NPs on breast cancer (MDA-MB-231) cells were significantly more than of pure ZnO NPs, while dual-doped and pure nanoparticles remained indifferent towards breast normal (MCF-10A) cells. In addition, we investigated the antimicrobial activity against harmful bacteria. [ABSTRACT FROM AUTHOR]

Six previously unknown triterpene glycosides, pacificusosides L–Q (1–6), and two previously known triterpene glycosides, cucumariosides B1 (7) and A5 (8), were isolated from an alcoholic extract of Pacific sun star, Solaster pacificus. The structures of 1–6 were determined using 1D and 2D NMR, ESIMS, and chemical modifications. Compound 1 is a rare type of triterpene glycoside with non-holostane aglycon, having a linear trisaccharide carbohydrate chain. Pacificusosides M–P (2–5) have new structures containing a Δ8(9)-3,16,18-trihydroxy tetracyclic triterpene moiety. This tetracyclic fragment in sea star or sea cucumber triterpene glycosides was described for the first time. All the compounds under study exhibit low or moderate cytotoxic activity against colorectal carcinoma HCT 116 cells, and breast cancer MDA-MB-231 cells were assessed by MTS assay. Compound 2 effectively suppresses the colony formation of cancer cells at a non-toxic concentration, using the soft-agar assay. A scratch assay has shown a significant anti-invasive potential of compound 2 against HCT 116 cells, but not against MDA-MB-231 cells.

Simple Summary: Triple negative breast cancer (TNBC) is one of the most challenging and hard to treat breast cancer types due to the lack of the receptor targets that are commonly found in breast cancers. It is aggressive in nature with a high recurrence rate. Chemotherapy, radiotherapy, and surgery are the available options. However, conventional chemotherapy drugs have not been effective and new treatment strategies are needed. To this end, we tested SYA014, a compound that binds to the sigma-2 receptor, for its anticancer properties against two different TNBC cell lines. SYA014 was able to kill the cancer cells by interfering with key cellular events associated with cell proliferation. SYA014 induced cytotoxicity in the TNBC cell lines and was evaluated for the involvement of the sigma-2 receptor. Finally, SYA014 was tested in combination with the well-known anticancer drug, cisplatin, in both TNBC cells and non-cancer cells, to improve the treatment outcome. Triple negative breast cancer (TNBC) is a type of breast cancer associated with early metastasis, poor prognosis, high relapse rates, and mortality. Previously, we demonstrated that SYA013, a selective σ2RL, could inhibit cell proliferation, suppress migration, reduce invasion, and induce mitochondria-mediated apoptosis in MDA-MB-231 cell lines, although we were unable to demonstrate the direct involvement of sigma receptors. This study aimed to determine the anticancer properties and mechanisms of action of SYA014, [4-(4-(4-chlorophenyl)-1,4-diazepan-1-yl)-1-(4-fluorophenyl)butan-1-one oxime], an oxime analogue of SYA013, the contribution of its sigma-2 receptor (σ2R) binding, and its possible synergistic use with cisplatin to improve anticancer properties in two TNBC cell lines, MDA-MB-231 (Caucasian) and MDA-MB-468 (Black). In the present investigation, we have shown that SYA014 displays anticancer properties against cell proliferation, survival, metastasis and apoptosis in the two TNBC cell lines. Furthermore, a mechanistic investigation was conducted to identify the apoptotic pathway by which SYA014 induces cell death in MDA-MB-231 cells. Since SYA014 has a higher binding affinity for σ2R compared to σ1R, we tested the role of σ2R on the antiproliferative property of SYA014 with a σ2R blockade. We also attempted to evaluate the combination effect of SYA014 with cisplatin in TNBC cells. [ABSTRACT FROM AUTHOR]

The purpose of current research was to assess the apoptotic effects of biofabrication silver nanoparticles (AgNPs) mediated by the aqueous extract of Phlomis armeniaca on human breast cancer cells (MCF-7 and MDA-MB-231) in monolayer (2D) and spheroid (3D) cultures. The biosynthesized AgNPs were characterized by UV–Vis spectrophotometer (the peaks of resonances at 432 nm), scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometry (EDS). 1–20 µM/mL AgNPs were applied to MCF-7 and MDA-MB-231 cell lines to determine IC50 values at 24, 48 and 72nd h and were found to be 10 µM/mL for both cell lines. Immunohistochemical staining results of BrdU, TUNEL, caspase-3 and Endo G in both 2D and 3D cultures and gene expression levels of caspases (caspase-3, -8 and -9) and Endo G were evaluated. Moreover, the total oxidant/antioxidant status (TOS–TAS) due to AgNPs application in both cell culture mediums was evaluated. AgNPs treatment results in both cell lines in both 2D and 3D cultures showed a significant decrease in the BrdU labeling index, while large amounts of cells were labelled with TUNEL and Endo G. In 2D culture, Endo G expression increased in MCF-7 cells at 48 and 72nd hours, while it increased significantly in MDA-MB-231 cells at all hours. OSI results show that ROS production is increased in cell medium treated with AgNPs. In conclusion, AgNPs mediated by Phlomis armeniaca, synthesized by a green method, successfully induced damage to mitochondria, resulting in cell cycle arrest and consequent cell proliferation blockade and death in both MCF-7 and MDA-MB-231 cells. [ABSTRACT FROM AUTHOR]

Phragmanthera austroarabica (Loranthaceae), a semi-parasitic plant, is well known for its high content of polyphenols that are responsible for its antioxidant and anti-inflammatory activities. Gallic acid, catechin, and methyl gallate are bioactive metabolites of common occurrence in the family of Loranthaceae. Herein, the concentrations of these bioactive metabolites were assessed using high-performance thin layer chromatography (HPTLC). Methyl gallate, catechin, and gallic acid were scanned at 280 nm. Their concentrations were assessed as 14.5, 6.5 and 43.6 mg/g of plant dry extract, respectively. Phragmanthera austroarabica extract as well as the three pure compounds were evaluated regarding the cytotoxic activity. The plant extract exhibited promising cytotoxic activity against MDA-MB-231 breast cells with the IC50 value of 19.8 μg/mL while the tested pure compounds displayed IC50 values in the range of 21.26–29.6 μg/mL. For apoptosis investigation, P. austroarabica induced apoptotic cell death by 111-fold change and necrosis by 9.31-fold change. It also activated the proapoptotic genes markers and inhibited the antiapoptotic gene, validating the apoptosis mechanism. Moreover, in vivo studies revealed a significant reduction in the breast tumor volume and weight in solid Ehrlich carcinoma (SEC) mice. The treatment of SEC mice with P. austroarabica extract improved both hematological and biochemical parameters with amelioration in the liver and kidney histopathology to near normal. Taken together, P. austroarabica extract exhibited promising anti-cancer activity through an apoptosis-induction. [ABSTRACT FROM AUTHOR]

Breast cancer is the primary cause of cancer‐related death in females, wherein increased mortality of breast cancer patients is recorded worldwide. Zingiberene is a monocyclic sesquiterpene from the ginger plant and has many pharmacological benefits. In this exploration, we assessed the anticancer actions of Zingiberene against the 7,12‐dimethylbenz(a)anthracene (DMBA)‐stimulated mammary carcinogenesis in rats and MDA‐MB‐231 cells. Breast cancer was induced in the Female Sprague‐Dawley rats through the 25 mg/kg of DMBA in 0.5 ml of corn oil and then treated with 20 and 40 mg/kg of Zingiberene, respectively. The body weight of animals and tumor volume was measured. Hematological parameters, transaminases, lipid profile, lipid peroxidation, and antioxidants status were scrutinized using standard techniques. The estrogen receptor‐α and inflammatory markers were inspected by using respective assay kits. Histological damage scores were determined. In vitro experiments were conducted to scrutinize Zingiberene's effect on cell viability and apoptotic cell death in MDA‐MB‐231 cells. Zingiberene substantially modulated the DMBA‐stimulated physiological and hematological changes and decreased the transaminases, and lipid peroxidation in the DMBA‐stimulated animals. Zingiberene also elevated the antioxidant level and suppressed the inflammatory markers. Histological study revealed the protective effects of Zingiberene. The viability of MDA‐MB‐231 cells was noticeably diminished by the Zingiberene, thus inducing apoptotic cell death. Overall, our findings reliably proved the anticancer potential of Zingiberene against the DMBA‐stimulated mammary tumorigenesis, and it could be a promising chemotherapeutic agent. [ABSTRACT FROM AUTHOR]

Cancer cells communicate within the tumor microenvironment (TME) through extracellular vesicles (EVs), which act as crucial messengers in intercellular communication, transporting biomolecules to facilitate cancer progression. Ubiquitin-like 3 (UBL3) facilitates protein sorting into small EVs as a post-translational modifier. However, the effect of UBL3 overexpression in EV-mediated protein secretion has not been investigated yet. This study aimed to investigate the effect of UBL3 overexpression in enhancing EV-mediated Achilles protein secretion in MDA-MB-231 (MM) cells by a dual-reporter system integrating Akaluc and Achilles tagged with Ubiquitin where self-cleaving P2A linker connects Akaluc and Achilles. MM cells stably expressing Ubiquitin-Akaluc-P2A-Achilles (Ubi-Aka/Achi) were generated. In our study, both the bioluminescence of Ubiquitin-Akaluc (Ubi-Aka) and the fluorescence of Achilles secretion were observed. The intensity of Ubi-Aka was thirty times lower, while the Achilles was four times lower than the intensity of corresponding cells. The ratio of Ubi-Aka and Achilles in conditioned media (CM) was 7.5. They were also detected within EVs using an EV uptake luciferase assay and fluorescence imaging. To investigate the effect of the UBL3 overexpression in CM, Ubi-Aka/Achi was transiently transfected into MM-UBL3-KO, MM, and MM-Flag-UBL3 cells. We found that the relative fluorescence expression of Achilles in CM of MM-UBL3-KO, MM, and MM-Flag-UBL3 cells was 30 %, 28 %, and 45 %, respectively. These findings demonstrated that UBL3 overexpression enhances EV-mediated Achilles protein secretion in CM of MM cells. Targeting UBL3 could lead to novel therapies for cancer metastasis by reducing the secretion of pro-metastatic proteins, thereby inhibiting disease progression., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Breast cancer (BC) is the most prevalent malignancy among women, with millions of newly diagnosed cases emerging annually. Therefore, identifying novel pharmaceuticals for therapeutic purposes is imperative. Several natural compounds and their products have demonstrated potential in the treatment of cancer. This study examined the effects of the ginger derivative 1-dehydro-6-gingerdione (1-D-6-G) on BC and its mechanisms of action. MTT and colony formation assays were used to check the anticancer effect of 1-D-6-G. Then the anticancer mechanism of 1-D-6-G was predicted using proteomics analysis. The molecular pathway was verified by qRT-PCR and immunobloting analysis. Additionally, the anticancer properties of 1-D-6-G were investigated in vivo using xenograft mice model. Finally, an in silico study was conducted to examine the interaction of 1-D-6-G and pathway-related proteins. MTT and colony formation assay results indicated that 1-D-6-G has potent cytotoxic properties against BC cells. Proteomic analysis revealed that the anticancer mechanism of 1-D-6-G on MDA-MB-231 cells is associated with the ferroptosis signaling pathway. In addition, qRT-PCR and immunoblotting analyses revealed that the cytotoxic effects of 1-D-6-G on MDA-MB-231 cells were associated with ferroptosis signaling induction. Our in vivo results further confirmed the in vitro findings. The administration of 1-D-6-G for 14 days exhibited anticancer properties in xenograft mice by stimulating the ferroptosis pathway without causing damage to essential organs such as the liver and kidneys. Additionally, in silico results confirmed the structural stability of the molecular interaction between 1-D-6-G and ferroptosis target proteins. Our findings indicate that 1-D-6-G has the potential to serve as a novel therapeutic agent for inhibiting BC progression by targeting the ferroptosis pathway., (© 2024 The Author(s). Phytotherapy Research published by John Wiley & Sons Ltd.)

Breast cancer recurrence is associated with the growth of disseminated cancer cells that separate from the primary tumor before surgical treatment and hormonal therapy and form a metastatic niche in distant organs. We previously demonstrated that IGFBP6 expression is associated with the risk of early relapse of luminal breast cancer. Knockdown of IGFBP6 in MDA-MB-231 breast cancer cells increased their invasiveness, proliferation, and metastatic potential. In addition, the knockdown of IGFBP6 leads to impaired lipid metabolism. In this study, we demonstrated that the knockdown of the IGFBP6 gene, a highly selective inhibitor of IGF-II, led to a significant decline in the number of secreted extracellular vesicles (EVs) and altered cholesterol metabolism in MDA-MB-231 cells. Knockdown of IGFBP6 led to a decrease in the essential proteins responsible for the biogenesis of cholesterol LDLR and LSS, which reduced the amount by more than 13 times. In addition, the knockdown of IGFBP6 led to a possible change in the profile of adhesion molecules on the surface of EVs. The expression of L1CAM, IGSF3, EpCAM, CD24, and CD44 decreased, and the expression of EGFR increased. We can conclude that the negative prognostic value of low expression of this gene could be associated with increased activity of IGF2 in tumor-associated fibroblasts due to low secretion of IGFBP6 by tumor cells. In addition, changing the profile of adhesion molecules on the surface of tumor EVs may contribute to the more efficient formation of metastatic niches., (Copyright © 2024 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Previous investigations have shown that high glucose can promote breast cancer progression. However, the relationship between high glucose microenvironment and triple-negative breast cancer (TNBC) remains to be explored. In this study, we performed RNA-seq to explore the effect of short-term high glucose and long-term high glucose on MDA-MB-231 cell line. A total of 896 highly ranked differentially expressed genes (DEGs) were identified, including 57 DEGs of short-term high glucose group and 839 DEGs of long-term high glucose group. The DEGs of short-term high glucose group were mainly associated with IL-17 signaling pathway. Nonetheless, the DEGs of long-term high glucose group were primarily involved in IL-17 signaling pathway, MAPK signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway in diabetic complications, Toll-like receptor signaling pathway, and VEGF signaling pathway. Additionally, 8 hub genes of short-term high glucose group were enriched in metabolic pathway. Moreover, 10 hub genes of long-term high glucose group were enriched in ribosome pathway. Subsequently, in vitro experiment results found that high glucose can promote cell proliferation, and has a time accumulation effect. In addition, high glucose can induce the accumulation of inflammatory factors and promote angiogenesis. Collectively, these findings provide novel insights into the effect of diabetes mellitus type 2 (T2DM) on TNBC., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A new fluorescent ratiometric switch (BOHB) was developed for swift and selective detection of cyanide ions in aqueous media without any interference from other competitive anions. Upon gradual addition of cyanide ions into the probe solution, a prominent fluorescence color change from yellow to cyan was observed under a UV chamber. The fluorescence changes thus observed were ratiometric, and the detection limit of this new probe was found to be (22.1 ± 0.89) μM, suggesting that the efficiency of BOHB for the detection of cyanide ions is brilliant even at a minute level. The blue shift in fluorescence intensity upon the addition of cyanide ions was attributed to the deprotonation mechanism of acidic protons present in BOHB. This phenomenon was further explored using 1 H-NMR study, which supported the mechanism. Further, stability study was performed over a period of 5 days to prominently establish the stability of BOHB. The probe is also highly capable of recognizing CN - within a very short time-span (almost 15 seconds), thereby making it a brilliant fluorescent switch for the swift recognition of CN - . Furthermore, BOHB was employed for real water sample analysis to display its practical application. Besides, the easy-to-prepare dipstick experiment provides a simple, reusable and recyclable protocol for the suitable qualitative identification of CN - . Lastly, triple negative breast adenocarcinoma (MDA-MB-231) cells were made susceptible to CN - sensing in a biological system, thereby making BOHB a biomarker tool.