Types Of Breast Cancer Cells Research Articles

Abstract 6329: Edible Chinese mushroom-derived antioxidant, vialinin A, prevents breast cancer cell growth

Abstract Breast cancer ranks as the second most prevalent cancer worldwide, impacting millions annually, and stands as the leading cancer affecting women. Neoplasia occurs when free radicals, antioxidants, and reactive oxygen species increase in the cell, which can alter protein function and cause mutations and genomic instability. Current breast cancer treatments typically include chemotherapy and radiation. However, different breast cancer cell types have different antioxidative capacities, which allow them to resist these treatments, thereby reducing the efficacy of these expensive treatments. Several vitamins, antioxidants, and anti-inflammatory compounds have been tested for their effectiveness in preventing breast cancer. However, the role of vialinin A, an antioxidant and ubiquitin-specific peptidase inhibitor derived from edible Chinese mushrooms, is unknown. Therefore, in this study, we examined the chemopreventive effect of vialinin A in preventing breast cancer cell growth and migration. Human breast cancer cells (MCF-7) were treated with vialinin A in a time- and dose-dependent manner. Cell viability assay indicates that vialinin A prevents the growth of breast cancer cells in a dose-dependent manner. Further, vialinin also prevented the EGF-induced invasion of MCF-7 cells in a scratch assay. Vialinin A also prevented the EGF-induced trans-well migration of breast cancer cells. Vialinin A also regulated the growth factor-induced expression of various pro- and anti-apoptotic factors in breast cancer cells. Vialinin A also increased the activation of caspase-3 and cleavage of PARP in growth factor-treated breast cancer cells. Next, we plan to examine the chemopreventive efficacy of vialinin A in a nude mouse xenograft model. In conclusion, our results indicate that vialinin A could prevent breast cancer cell growth and invasion, suggesting its potential development as a chemopreventive drug. Citation Format: Malak Rafik, Afnan Khan, Kota V. Ramana. Edible Chinese mushroom-derived antioxidant, vialinin A, prevents breast cancer cell growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6329.

Abstract 1393: Functional analysis of mitochondria-targeting Wnt-inhibitors on metabolically distinct breast cancer cell types

Abstract Mitochondria are essential organelles responsible for energy production and survival. In cancer cells, mitochondrial function is often altered through metabolic reprogramming, which enhances their growth, survival, and resistance to therapy. Recent findings suggest that bi-directional crosstalk between Wnt signaling and mitochondrial function plays a crucial role in tumorigenesis, as well as in the differentiation and self-renewal of stem cells. This study investigates the potential of targeting the interplay between Wnt signaling and mitochondrial function in breast cancer cells. We screened 71 agents known to alter Wnt signaling and assessed their impact on mitochondrial function and cell viability in BT474 and Hs578T breast cancer cell lines. The Mito Tox Index (MTI) obtained using the Agilent Seahorse XF MitoTox Assay was used as the parameter to evaluate the impact of test compounds on mitochondrial function. The screening identified Pyrvinium, Niclosamide, and Hexachlorophene as the most potent mitochondrial modulators. Pyrvinium and Niclosamide inhibited the mitochondrial electron transport chain, whereas Hexachlorophene acted as an uncoupler when the cells were exposed to the drugs for 24 hours. The mechanisms of mitochondrial perturbation induced by these drugs were further investigated using BT474 cells permeabilized with the Seahorse XF Plasma Membrane Permeabilizer (PMP), which selectively permeabilizes the cellular plasma membrane without affecting mitochondria integrity. This approach enabled detailed characterization of key components in mitochondrial function, including transporters, enzymes, and electron transport chain complexes. Our results indicated that Niclosamide inhibited complex I/II, either directly or indirectly, while Pyrvinium appeared to suppress mitochondrial function indirectly. Despite the different bioenergetic phenotypes of BT474 (highly oxidative) and Hs578T (highly glycolytic) cells, there was no significant difference in mitochondrial susceptibility to the three drugs. However, significant differential effects on ATP production rates were detected using the Agilent Seahorse XF Real-Time ATP Rate, BT474 cells exhibited a significant metabolic energy crisis in the presence of all three compounds, whereas Hs578T cells maintained stable total ATP production despite mitochondrial inhibition. This differential impact on ATP production rates corresponded directly to differences in cell viability, with BT474 cells showing higher susceptibility to these compounds. These findings suggest that the anti-cancer efficacy of mitochondrial modulators can vary depending on the metabolic phenotype of the target cell and should be considered in therapeutic design. Targeting mitochondrial function through Wnt signaling inhibitors presents a promising strategy for developing effective cancer therapies. Citation Format: Yoonseok Kam, Lisa Winer, Natalia Romero. Functional analysis of mitochondria-targeting Wnt-inhibitors on metabolically distinct breast cancer cell types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1393.

Anticancer Activity for MCF-7 Cell by Mechanism of BCL2 and p53 Expression from Nggorang Leaf Extracts (Salvia occidentalis sw.)

Based on previous study of Nggorang leaf extract (EDG) that had potential activity as an antiproliferative and increasing gene expression on T47D cancer cells, there are other types of cancer cells, including MCF-7 cancer cells. This research is to find out antiproliferative activity against MCF-7 cancer cells where this is another type of breast cancer cells. There are 8 groups. Every groups obtain treatment of different test materials. Using the MTT method and analyzing the effect of EDG on enhancement activity BCL2 and p53 expression on cells Cancer MCF-7 with which is compared with 5FU. The results of determining the amount of BCL2 and p53 expression and analyzed by SPSS by comparing between treatments and between stages of testing, namely potential as antiproliferation to cancer cells MCF-7 with a concentration of 274.55 ppm and 5FU at concentration 34.33ppm which is an effective dose. The higher the concentration of EDG given, the greater the number of MCF-7 cells that express the p53 gene and reduce the expression of the BCL2 gene. EDG had potential activity on MCF-7 cancer cells as preventive.

Dielectric Characterization of Breast Cancer Cells using Split-Rectangular Ring Resonator Sensor

Exploring a universal method to enhance the performance of metamaterials by quantifying the impact of gap capacitance is an intriguing topic for many researchers. However, achieving this through conventional methods is extremely challenging. In this paper, we present a microwave sensor designed to characterize cancerous cells based on their electrical properties. The proposed design features a split rectangular ring resonator placed on a flame-retardant four (FR-4) substrate. The sensor aims to achieve high sensitivity and quality factors through the unique characteristics of the metamaterial structure in the GHz frequency range. Through simulations and experimental measurements, we demonstrate the sensor's effective capabilities in detecting cancer. The high sensitivity for both simulation and measurement, is estimated at 10 %. The simulations and validation confirm that this biosensor exhibits significant frequency shifts and high sensitivity. Our proposed configurations highlight the microwave sensor's potential for detecting six different breast cancer cell types: HSS-2, HS578-T_nm, MCF-2, MCF-10A_nm, T-47D, and T-47D_nm. Based on the existing literatures, the sensitivity of the proposed sensor is determined to be greater.

Layered Double Hydroxide Nanoparticles Loaded with Resveratrol Inhibit Glycolysis and Show Efficacy in the Treatment of Breast Cancer.

Breast cancer is one of the most common cancers among women. Tumor cell proliferation is highly dependent on aerobic glycolysis, so regulating aerobic glycolysis in breast cancer cells is a promising therapeutic strategy. Resveratrol (Res), as a potential new anti-breast cancer drug, has been shown to regulate the glycolysis of cancer cells and inhibit the metastasis and recurrence of breast cancer. The nano drug delivery system can regulate the aerobic glycolysis metabolism by targeting the signaling factors and reaction products of the tumor aerobic glycolysis process to enhance the anti-tumor effect. A new albumin-modified layered double hydroxide resveratrol dosage form (BSA@LDHs-Res) was synthesized by hydrothermal co-precipitation. Characterization was carried out to determine the successful synthesis of the nanocarrier system. The bioactivity, glycolytic activity and biocompatibility were examined by in vitro cellular assays; in vivo experiments were performed to further evaluate the anti-tumor effects of the BSA@LDHs-Res dosage form for breast cancer. In this study, we obtained for the first time a bovine serum albumin-modified BSA@LDHs-Res loaded dosage form, which was able to enter breast cancer cells SKBR3 and MDA-MB-231 via endocytosis and successfully escaped from lysosomal capture. BSA@LDHs-Res inhibited the proliferation, migration, and invasion of two types of breast cancer cells, induced apoptosis, and promoted the reduction of mitochondrial membrane potential and ROS. BSA@LDHs-Res inhibited the expression and viability of the key enzymes of glycolysis, hexokinase 2 (HK2), pyruvate kinase (PK), and lactate dehydrogenase, resulting in decreased glucose consumption, decreased lactate accumulation, and decreased intracellular ATP levels. BSA@LDHs-Res was examined in the mouse model with good anti-tumor effects. BSA@LDHs-Res is an efficient nanoreagent for the treatment of breast cancer. The albumin-modified resveratrol layered double hydroxide delivery system developed in this study will provide some theoretical references for further research and clinical application of tumor aerobic glycolysis.

Dehydrodiisoeugenol targets the PLK1-p53 axis to inhibit breast cancer cell cycle.

There are about 2,300,000 new cases of breast cancer worldwide each year. Breast cancer has become the first most common cancer in the world and the leading cause of death among women. At the same time, chemotherapy resistance in patients with advanced breast cancer is still a serious challenge. Alpinia Katsumadai Hayata (AKH), as a traditional Chinese herbal medicine, has a wide range of pharmacological activities. Related studies have found that many compounds in AKH have anti-breast cancer activity. However, it is still worth exploring which component is the main active component of AKH in inhibiting breast cancer and its mechanism of action. In this study, dehydrodiisoeugenol (DHIE) was screened as the main active ingredient of AKH against breast cancer based on LC-MS combined with drug similarity and disease enrichment analysis. WGCNA, network pharmacology, molecular docking, transcriptome sequencing analysis, immune infiltration analysis and single-cell sequencing were used to explore the mechanism of DHIE on breast cancer. CCK-8, flow cytometry and Western blot were used to verify the results in vitro. The efficacy of the drugs was verified in vivo by constructing a subcutaneous tumor-bearing mouse model. Our research showed that DHIE and breast cancer enriched core gene targets mainly act on epithelial cells in breast cancer tissues and significantly inhibit the growth of breast cancer by affecting the PLK1-p53 signaling axis to arrest the breast cancer cell cycle at G0/G1 phase. Further analysis showed that although DHIE had opposite regulatory effects on different isoforms of p53 in different types of breast cancer cells, they eventually caused cell cycle arrest. In addition, in vivo studies showed that DHIE reduced tumor burden, significantly reduced the infiltration level of tumor proliferation-related marker Ki-67, and inhibited the expression of PLK1 in the mouse model, which was further enhanced when combined with DOX. Collectively, our study suggests that DHIE in AHK may eventually induce cell cycle arrest and inhibit breast cancer growth by regulating the PLK1-p53 signaling axis, which may provide a new therapeutic strategy for breast cancer. However, the specific mechanisms by which DHIE regulates p53 in different subtypes of breast cancer and the advantages of chemotherapeutic combinations compared with other drugs are still worth exploring.

Pharmacological CDK4/6 inhibition promotes vulnerability to lysosomotropic agents in breast cancer

Breast cancer is a leading cause of mortality worldwide. Pharmacological inhibitors of cyclin-dependent kinases (CDK) 4 and 6 (CDK4/6i) inhibit breast cancer growth by inducing a senescent-like state. However, the long-term treatment efficacy remains limited by the development of drug resistance, so clearance of senescent-like cancer cells may extend the durability of treatment. However, we show here that while CDK4/6i-treated breast cancer cells exhibit various senescence-associated phenotypes, they remain insensitive to common senolytic compounds. By searching for novel vulnerabilities, we identify a significantly increased lysosomal mass and altered lysosomal structure across various breast cancer cell types upon exposure to CDK4/6i in preclinical systems and clinical specimens. We demonstrate that these CDK4/6i-induced lysosomal alterations render breast cancer cells sensitive to lysosomotropic agents, such as L-leucyl-L-leucine methyl ester (LLOMe) and salinomycin. Importantly, sequential treatment with CDK4/6i and lysosomotropic agents effectively reduces the growth of both hormone receptor-positive (HR+) and subsets of triple-negative breast cancer (TNBC) cells in vivo. This sequential therapeutic strategy offers a promising approach to eliminate CDK4/6i-induced senescent(-like) cells, potentially reducing tumor recurrence and enhancing the overall efficacy of breast cancer therapy.

Therapeutic Targeting of Quercetin to Breast Cancer Cells under In Vitro Conditions: A Systematic Review

Background: Quercetin (QT) is an effective plant compound in treating various diseases, including certain types of cancer. Therefore, this systematic review study was conducted to investigate the positive effects of quercetin (QT) on different breast cancer cell lines under in vitro conditions. Objective: The purpose of this study was to explore the beneficial effects of quercetin (QT) on various breast cancer cell lines in an in vitro setting. Methods: Using various databases, including PubMed, Scopus, Science Direct, and Google Scholar, we searched for publications from 2018 to May 2024 based on relevant terms and keywords for this systematic review. Inclusion criteria focused on English, open access, and original studies that exclusively examined the effects of QT on breast cancer cell types in vitro. Results: From the initial search, 1308 publications were identified. However, only 46 met the inclusion criteria and were included in this systematic review. Conclusion: In summary, quercetin (QT) shows anti-tumor effects on different breast cancer cell lines by activating the PI3K/AKT/mTOR, IGF1/IGF1R, MAPK, Transforming Growth Factor-β (TGFβ), and JAK/STAT1 pathways. Nonetheless, further extensive animal and clinical studies are essential to draw definitive conclusions.

Key Magnetized Exosomes for Effective Targeted Delivery of Doxorubicin Against Breast Cancer Cell Types in Mice Model [Letter

Key Magnetized Exosomes for Effective Targeted Delivery of Doxorubicin Against Breast Cancer Cell Types in Mice Model [Letter

Cell type specific drug repurposing for breast cancer by integrating single-cell RNA sequencing and molecular docking simulation

Abstract. Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer-related deaths among women. Despite the widespread use of chemotherapy and radiotherapy, there is an urgent need for novel treatments. This study focuses on drug repurposing for breast cancer using single-cell RNA sequencing (scRNA-seq) data. By analyzing differentially expressed genes across various breast cancer cell types, we identified potential protein targets. We then used Drug2cell to generate top cancer-related drug candidates, followed by molecular featurization of proteins and drugs. Drug-target interactions were analyzed through molecular docking, and the top drug candidates for each cell type were ranked. Our data analysis annotated ten cell types from breast cancer scRNA-seq data. Using the top ten differentially expressed genes, we identified over a hundred protein targets and conducted molecular docking analysis. Fourteen drugs, including doxorubicin and everolimus, were repurposed with supporting clinical evidence for their effectiveness in breast cancer treatment. Overall, this drug-repurposing strategy, combined with scRNA-seq data, identified several cell-type-specific drugs, enhancing therapeutic target discovery and improving treatment success rates for breast cancer.

Poly(Epsilon-Lysine) Dendrons Inhibit Proliferation in HER2-Overexpressing SKBR3 Breast Cancer Cells at Levels Higher than the Low-Expressing MDA-MB-231 Phenotype and Independently from the Presentation of HER2 Bioligands in Their Structure.

Among the known breast cancers, the subtype with HER2 receptors-overexpressing cells is associated with a poor prognosis. The adopted monoclonal antibody Trastuzumab has improved clinical outcomes, but it is associated with drug resistance and relatively high costs. The present work adopted the peptide solid-phase synthesis method to synthesise branched poly(ε-lysine) peptide dendrons with 8 branching arms integrating, at their carboxy terminal molecular root, either an arginine or the HER2 receptor-binding sequence LSYCCK or the scramble sequence CSCLYK. These dendrons were synthesised in quantities higher than 100 mg/batch and with a purity exceeding 95%. When tested with two types of breast cancer cells, the dendrons led to levels of inhibition in the HER2 receptor-overexpressing breast cancer cells (SKBR3) comparable to Trastuzumab and higher than breast cancer cells with low receptor expression (MDA-MB-231) where inhibition was more moderate. Noticeably, the presence of the amino acid sequence LSYCCK at the dendron molecular root did not appear to produce any additional inhibitory effect. This was demonstrated also when the scramble sequence CSCLYK was integrated into the dendron and by the lack of any antiproliferative effect by the control linear target sequence. The specific inhibitory effect on proliferation was finally proven by the absence of cytotoxicity and normal expression of the cell migration marker N-Cadherin. Therefore, the present study shows the potential of poly(ε-lysine) dendrons as a cost-effective alternative to Trastuzumab in the treatment of HER2-positive breast cancer.

Comparison of the effects of crizotinib as monotherapy and as combination therapy with butyric acid on different breast cancer cells.

In recent years, there have been significant developments using combined therapies in cancer treatment. The present study aimed to determine the effects of using crizotinib alone and in combination with butyric acid on different types of breast cancer cells. A total of three different breast cancer models were used: MDA-MB-231, a triple negative model; MCF-7, a Luminal A model; and SKBR-3 cell line, a human epidermal growth factor receptor 2 positive model. In the experiments, proliferation rates and cell index values were obtained using the xCELLigence RTCA DP System, and mitotic index, bromodeoxyuridine labeling index and caspase activity were evaluated as cell kinetics parameters. The results showed that while proliferation rates, cell index values, mitotic index and bromodeoxyuridine labeling index decreased, caspase activity values increased. These results demonstrated that the combined application was more effective than the monotherapy application and could be used at lower concentrations than those drugs applied as monotherapy.

Estro-Androgenic Disrupting Effects of Halogenated Disinfection Byproducts: A Comprehensive Evaluation and Comparison.

Drinking water halogenated disinfection byproducts (DBPs) have become an increasing health concern. However, the endocrine-disrupting effects of DBPs have not been well evaluated, and the limited available data have inhibited a comprehensive understanding of their health risks. In this study, a total of 43 DBPs were evaluated for their estro-androgenic effects using two types of human breast cancer cells. Among the tested DBPs, 16 exhibited estrogenic/antiestrogenic/androgenic/antiandrogenic effects, and the effects could be observed even at concentrations typically detected in drinking water. Iodinated and polyhalogenated DBPs generally showed higher effects than other species. For a broader comparison, DBP endocrine-disrupting effect data from this study and previous studies were summarized. It was found that the endocrine disruption efficacy of DBPs followed the rank order of iodinated > brominated > chlorinated species, and halophenolic DBPs were potential endocrine-disrupting compounds. Moreover, molecular docking results demonstrated that the binding of DBPs to estro-androgenic receptors was dominated by hydrophobic bonding, hydrogen bonding, halogen bonding, and van der Waals forces. The force strength and molecular volume were related to the magnitude of the estro-androgenic effects. Iodinated DBPs and polyhalogenated DBPs tended to have larger binding forces than other analogues and thus exhibited stronger effects.

Key Magnetized Exosomes for Effective Targeted Delivery of Doxorubicin Against Breast Cancer Cell Types in Mice Model.

Exosomes (Exos) are promising drug delivery systems due to their low immunogenicity, minimal toxicity, high biocompatibility, and effective delivery capabilities. However, addressing the cardiotoxicity and other toxic side effects associated with anthracyclines has proven challenging. In this study, we loaded doxorubicin (Dox) into Exos derived from human placental mesenchymal stem cells (MSCs) and modified them with carboxylated Fe3O4 nanoparticles (NPs) to create an Exo-Dox-NP delivery system. Using an external magnetic force (MF), we regulated the distribution of Exos for targeted Dox delivery in breast cancer treatment. We characterized and determined the drug-loading efficiency of Exo-Dox-NPs, their uptake by tumor cells, and the modulation of drug release. The therapeutic efficacy of Exo-Dox-NPs was evaluated through both in vitro and in vivo anti-tumor experiments. Our results indicated that Exo-Dox-NPs remain stable in the bloodstream while releasing the drug in the acidic environment of tumor cells and their lysosomes. As a drug delivery system, Exo-Dox-NPs enhanced Dox absorption by tumor cells, demonstrating high targeting specificity. Moreover, Exo-Dox-NPs inhibited the migration of breast cancer cells, as confirmed by scratch migration and Transwell Matrigel invasion assays. In vivo experiments confirmed the effective targeting and delivery of Dox to malignant tumors using Exo-Dox-NPs/MFs, with the Exo-Dox-NP/MF formulation exhibiting the most potent anti-tumor activity. The utilization of Exos as carriers for Dox showed promising efficacy in breast cancer management. Carboxylated Fe3O4 NPs demonstrated to be suitable targeting agents, potentially advancing the development of natural nanocarriers for combination cancer therapy.

The effects of perfluorooctanoic acid on breast cancer metastasis depend on the phenotypes of the cancer cells: An in vivo study with zebrafish xenograft model

The effects of perfluorooctanoic acid on breast cancer metastasis depend on the phenotypes of the cancer cells: An in vivo study with zebrafish xenograft model

The Proapoptotic Action of Pyrrolidinedione-Thiazolidinone Hybrids towards Human Breast Carcinoma Cells Does Not Depend on Their Genotype.

The development of new, effective agents for the treatment of breast cancer remains a high-priority task in oncology. A strategy of treatment for this pathology depends significantly on the genotype and phenotype of human breast cancer cells. We aimed to investigate the antitumor activity of new pyrrolidinedione-thiazolidinone hybrid molecules Les-6287, Les-6294, and Les-6328 towards different types of human breast cancer cells of MDA-MB-231, MCF-7, T-47D, and HCC1954 lines and murine breast cancer 4T1 cells by using the MTT, clonogenic and [3H]-Thymidine incorporation assays, flow cytometry, ELISA, and qPCR. The studied hybrids possessed toxicity towards the mentioned tumor cells, with the IC50 ranging from 1.37 to 21.85 µM. Simultaneously, these derivatives showed low toxicity towards the pseudonormal human breast epithelial cells of the MCF-10A line (IC50 > 93.01 µM). Les-6287 at 1 µM fully inhibited the formation of colonies of the MCF-7, MDA-MB-231, and HCC1954 cells, while Les-6294 and Les-6328 did that at 2.5 and 5 µM, respectively. Les-6287 suppressed DNA biosynthesis in the MCF-7, MDA-MB-231, and HCC1954 cells. At the same time, such an effect on the MCF-10A cells was significantly lower. Les-6287 induces apoptosis using extrinsic and intrinsic pathways via a decrease in the mitochondrial membrane potential, increasing the activity of caspases 3/7, 8, 9, and 10 in all immunohistochemically different human breast cancer cells. Les-6287 decreased the concentration of the metastasis- and invasion-related proteins MMP-2, MMP-9, and ICAM-1. It did not induce autophagy in treated cells. In conclusion, the results of our study suggest that the synthesized hybrid pyrrolidinedione-thiazolidinones might be promising agents for treating breast tumors of different types.

Lindqvist-type Polyoxometalates Act as Anti-breast Cancer Drugs via Mitophagy-induced Apoptosis.

Lindqvist-type polyoxometalates (POMs) exhibit potential antitumor activities. This study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying mechanism. Using different cancer cell lines, the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side strains. Cell colony formation assay, autophagy detection, mitochondrial observation, qRT-PCR, Western blotting, and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related mechanism. MO-4, a Lindqvist-type POM linking a proline at its side strain, was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer cells. It was found that MO-4 induced the apoptosis of multiple types of breast cancer cells. Mechanistically, MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species (ROS) levels and resulting in apoptosis. In vivo, breast tumor growth and distant metastasis were significantly reduced following MO-4 treatment. Collectively, the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer.

Enzyme-Instructed Self-Assembly of Peptides Induced by Tyrosine Phosphatase in Breast Cancer Cells.

Enzyme induced self-assembly (EISA) leverages the expression of locally diseased enzymes within tumors to facilitate the self-assembly of small molecules into larger nanostructures capable of targeting cancer cells. Eye absent (EYA) is a tyrosine phosphatase enzyme found to be overexpressed in specific types of drug-resistant breast cancer cells. Utilizing this overexpression, we propose the synthesis of small peptides that can undergo self-assembly induced by the EYA tyrosine phosphatase. Our research demonstrates the presence of the EYA protein in Triple-Negative Breast Cancer cells by using the western blot. We then study the interaction between EYA's Tyr-phosphatase and the peptides P1and P2, and validate the successful intracellular self-assembly of fluorescence-tagged peptides in TNBC cells. These findings are reinforced by viability assays demonstrating the efficacy of the combination therapy of peptides and anticancer drugs for decreasing viability of TNBC cells. This paves the way for investigations into the discovery of new therapeutics for breast cancers.

Self-assembling peptides induced by eyes absent enzyme to boost the efficacy of doxorubicin therapy in drug-resistant breast cancer cells

Self-assembling peptides induced by eyes absent enzyme to boost the efficacy of doxorubicin therapy in drug-resistant breast cancer cells

A lactate-responsive gene signature predicts the prognosis and immunotherapeutic response of patients with triple-negative breast cancer.

Increased glycolytic activity and lactate production are characteristic features of triple-negative breast cancer (TNBC). The aim of this study was to determine whether a subset of lactate-responsive genes (LRGs) could be used to classify TNBC subtypes and predict patient outcomes. Lactate levels were initially measured in different breast cancer (BC) cell types. Subsequently, MDA-MB-231 cells treated with 2-Deoxy-d-glucose or l-lactate were subjected to RNA sequencing (RNA-seq). The gene set variation analysis algorithm was utilized to calculate the lactate-responsive score, conduct a differential analysis, and establish an association with the extent of immune infiltration. Consensus clustering was then employed to classify TNBC patients. Tumor immune dysfunction and exclusion, cibersort, single-sample gene set enrichment analysis, and EPIC, were used to compare the tumor-infiltrating immune cells between TNBC subtypes and predict the response to immunotherapy. Furthermore, a prognostic model was developed by combining 98 machine learning algorithms, to assess the predictive significance of the LRG signature. The predictive value of immune infiltration and the immunotherapy response was also assessed. Finally, the association between lactate and various anticancer drugs was examined based on expression profile similarity principles. We found that the lactate levels of TNBC cells were significantly higher than those of other BC cell lines. Through RNA-seq, we identified 14 differentially expressed LRGs in TNBC cells under varying lactate levels. Notably, this LRG signature was associated with interleukin-17 signaling pathway dysregulation, suggesting a link between lactate metabolism and immune impairment. Furthermore, the LRG signature was used to categorize TNBC into two distinct subtypes, whereby Subtype A was characterized by immunosuppression, whereas Subtype B was characterized by immune activation. We identified an LRG signature in TNBC, which could be used to predict the prognosis of patients with TNBC and gauge their response to immunotherapy. Our findings may help guide the precision treatment of patients with TNBC.