Apoptosis In Breast Cancer Cells Research Articles

MLLT6/ATF2 Axis Restrains Breast Cancer Progression by Driving DDIT3/4 Expression.

Epigenetic deregulation is strongly associated with tumor progression. The identification of natural tumor suppressors to overcome cancer metastasis is urgent for cancer therapy. We investigate whether myeloid/lymphoid or mixed-lineage leukemia translocated (MLLT) family members contribute to breast cancer progression and found that high MLLT6 expression predicted a better prognosis and that gradually decreased MLLT6 expression was accompanied by breast cancer malignancy. MLLT6 was downregulated by hypoxia-induced enrichment of DNMT1 at the MLLT6 promoter. The results of in vitro functional experiments indicated that MLLT6 depletion promoted colony formation and cell migration, probably by hampering apoptosis. RNA profiling revealed that the apoptotic pathway was downregulated following stable knockdown of MLLT6. DNA damage-inducible transcript 3/4 (DDIT3/4) were among the top 10 downregulated genes and may have expression patterns similar to that of MLLT6. Restoring DDIT3/4 expression in cells with MLLT6 depletion blocked colony formation and cell migration and attenuated the successful colonization of breast cancer cells in vivo. We also determined that the transcription factor activating transcription factor 2 is a binding partner of MLLT6 and participates in the MLLT6/ATF2 axis, which was reinforced by inhibition of AKT signaling, in turn inducing DDIT3/4 expression by establishing an active chromatin structure at the DDIT3/4 gene promoters. As MLLT6 promotes breast cancer cell apoptosis by inducing DDIT3/4 expression during metastasis, it could be a novel tumor suppressor. Implications: Control of MLLT6 expression via inhibition of PI3K/AKT kinase activity is a potential therapeutic approach for the management of metastatic breast cancer.

Morchella conica, Morchella esculenta and Morchella delicosa Induce Apoptosis in Breast and Colon Cancer Cell Lines via Pro-apoptotic and Anti-apoptotic Regulation.

To explore the potential apoptotic mechanisms of 3 Morchella extracts (Morchella conica, Morchella esculenta and Morchella delicosa) on breast and colon cancer cell lines using apoptotic biomarkers. Human breast cell line (MCF-7) and colon cancer cell line (SW-480) were treated with methanol and ethanol extracts of 3 Morchella species with concentration ranging from 0.0625 to 2 mg/mL. After that their effects on gene expression of apoptosis related markers (pro-apoptotic markers including Bax, caspase-3, caspase-7, and caspase-9, and the antiapoptotic marker including Bcl-2) were determined using reverse transcription polymerase chain reaction. All Morchella extracts reduced breast and colon cancer cells proliferation at half inhibitory concentration (IC50) of 0.02 ±0.01 to 0.68 ±0.30 mg/mL. As expected, all Morchella extracts significantly increased gene expressions of Bax, caspase-3, caspase-7, and caspase-9 and downregulated the gene expression of Bcl-2 in MCF-7 and SW-480 cell lines (P<0.05). Morchella extracts demonstrated significant anti-proliferative activity against breast and colon cancer cell lines via an apoptosis induction mechanism. Anticancer activity of Morchella extracts and activation of apoptosis in breast and colon cancer cells suggest that it may be used to develop chemotherapeutic agents against cancer in future.

TRIM28 promotes tumor growth and metastasis in breast cancer by targeting the BRD7 protein for ubiquitination and degradation.

Bromodomain-containing protein 7 (BRD7) is downregulated and functions as a tumor suppressor in many types of cancers including breast cancer, and the dysregulation of BRD7 expression is closely related to the development and progression of breast cancer. Whereas little attention has been focused on the regulation of BRD7 protein levels in breast cancer, which needs to be further elucidated. The protein stability of BRD7 in breast cancer cells and BRD7 protein level in breast cancer tissues was examined by Western Blotting. The potential E3 ubiquitin ligase proteins that interact with the BRD7 was screened by coimmunoprecipitation combined with mass spectrometry analysis in MDA-MB-231 cells. We proved the interaction between BRD7 and tripartite motif containing 28 (TRIM28) through Co-Immunoprecipitation (Co-IP) and immunofluorescence assays. Co-IP and ubiquitination assay were used to explore the specific binding domain between BRD7 and TRIM28 and the ubiquitination site of BRD7. The effects of TRIM28 on the BRD7 protein stability and ubiquitination level was investigated by qPCR, Western Blot and Co-IP assay. CCK-8 and clone formation assays were carried out to assess the effect of TRIM28 on proliferation ability of breast cancer ells. Transwell assay and wound healing assay were used to investigate the effect of TRIM28 on breast cancer cell invasion and migration. Flow cytometry was used to detect the effect of TRIM28 on cell cycle and apoptosis of breast cancer cells. In addition, we confirmed effect of TRIM28 on tumor growth and metastasis by xenograft and metastatic mouse models. We designed some recovery assays to explore the role of recovery BRD7 in TRIM28-mediated promotion of malignant progression of breast cancer in vivo and in vitro. Finally, the clinical significance of TRIM28 and BRD7 was proved by immunohistochemistry. In this study, we demonstrated that BRD7 was an unstable protein and might be regulated by ubiquitination in breast cancer; furthermore, we found that the Coiled-Coil region of TRIM28 could directly bind to N-terminal of BRD7, and TRIM28 mediates BRD7 ubiquitination and degradation dependent on K21 by acting as a potential E3 ubiquitin ligase. Moreover, TRIM28 promoted cell proliferation, migration, invasion, xenograft tumor growth and metastasis, thus playing an oncogenic role in breast cancer. Furthermore, the restoration of BRD7 expression in breast cancer significantly reversed the promotional effects of TRIM28 on malignant progression both in vitro and in vivo. In addition, TRIM28 was highly expressed in the biopsy tissues of breast cancer, and its expression was negatively correlated with BRD7 expression and positively correlated with TNM stage and poor prognosis of BC patients. Our findings provide a novel mechanism by which TRIM28 significantly facilitates BRD7 ubiquitination and degradation, thus promoting breast cancer malignant progression. Targeting the TRIM28/BRD7 axis might be a novel potential strategy for the clinical diagnosis and treatment of breast cancer.

Investigating the Effect of EX-527 as SIRT1 Inhibitor in Breast Cancer Cell Line

Background: Breast cancer is one of the most common malignant and metastatic tumors worldwide that cause death in women. Therefore, preventing the growth and metastasis of cancerous cells is essential for enhancing the prognosis and efficacy of treatment for breast cancer. Sirtuin 1 (SIRT1) is a nicotinamide-adenine dinucleotide (NAD+)-dependent deacetylase that has been linked to a number of biological processes, including genomic stability, cell cycle, cell survival and cancer metastasis. EX-527 is a selective and potent SIRT1 inhibitor. Recent studies have revealed that SIRT1 has an oncogenic role in breast cancer. Objective: To evaluate the effect of EX-527 on the MCF-7 breast cancer cell line. Methods: MCF-7 was cultured in complete DMEM and treated with and without EX-527. Cell viability of the breast cancer cell line was evaluated by MTT assay and apoptosis by Annexin V/PI staining. Migration and invasion of breast cancer cells were determined by wound healing and transwell invasion assays, respectively. Results: Results revealed that EX-527 at a concentration of 25.30 µM was associated with a significant anti-proliferative effect and induction of apoptosis (98.3%) in breast cancer cells. Treatment with EX-527 was also associated with significant suppression of migration and invasion of MCF-7. Conclusions: The current investigation showed that inhibition of SIRT1 by EX-527 inhibits proliferation, migration, invasion and apoptosis of human breast cancer cells.

Mechanically Flexible Self-Healing Mg(II)-Metallogel: Approach of Triggering the ROS-Induced Apoptosis in Human Breast Cancer Cells.

A self-assembly-directed thixotropic metallohydrogel (i.e., Mg-Tetrakis) of Mg(II)-metal salt and N,N,N',N'-tetrakis(2-hydroxy-ethyl)ethylenediamine (i.e., Tetrakis) was successfully achieved. The organic chemical component N,N,N',N'-tetrakis(2-hydroxy-ethyl)ethylenediamine was used as a low-molecular-weight gelator, and water was employed as the gel-forming solvent. The fabricated supramolecular metallohydrogel promisingly depicted viscoelastic and mechanoelastic behaviors, which are interpreted through various rheological parameters. The thixotropic behavior of the metallohydrogel is also well characterized through this rheological study. Field emission scanning electron microscopy microstructural analyses were performed to visualize the morphological arrangements of the metallohydrogel. The anticancer properties of the synthesized metallogels are investigated through this work. The cytotoxic potential of the metallohydrogel on the MCF-7 breast cancer cell line is critically examined. Reducing the growth of breast cancer cell line MCF-7 through the treatment of gel on the colony formation assay has been explored through the work. The antimigratory potential of the metallohydrogel on the MCF-7 cell was also scrutinized. The anticancer effect of the fabricated metallohydrogel is inspected through various assay formation strategies, like wound healing assay, tumor spheroid inhibition assay, nuclear fragmentation assay, and so on. Quantitative reactive oxygen species analysis of the cancer cells by treatment with the metallohydrogel was also conducted through this study. The mechanistic apoptosis study was executed by studying the expression of various apoptotic markers like BAX, BCL2, PUMA, and NOXA.

Mutant P53 modulation by cryptolepine through cell cycle arrest and apoptosis in triple negative breast cancer

BackgroundTriple Negative Breast cancer is an aggressive breast cancer subtype. It has a more aggressive clinical course, an earlier age of onset, a larger propensity for metastasis, and worse clinical outcomes as evidenced by a higher risk of recurrence and a shorter survival rate. Currently, the primary options for TNBC treatment are surgery, radiation, and chemotherapy. These treatments however remain ineffective due to recurrence. However, given that p53 mutations have been identified in more than 60–88 % of TNBC, translating p53 into the clinical situation is particularly important in TNBC. In this study, we screened and evaluated the therapeutic potential of cryptolepine (CRP) in TNBC in-vitro models being an anti-malarial drug it could be repurposed as an anti-cancer therapeutic targeting TNBC. Moreover, the cytotoxicity activity of cryptolepine to TNBC cells and a detailed anti-tumor mechanism in mutant P53 has not been reported before. MethodsMTT assays were used to examine the cytotoxicity and cell viability activity of Cryptolepine in TNBC, non-TNBC T47D and MCF-7 and non-malignant MCF10A cells. Scratch wound and clonogenic assay was used to evaluate the cryptolepine’s effect on migration and colony forming ability of TNBC cells. Flow cytometry, MMP and DAPI was used to assess cell cycle arrest and cell apoptosis mechanism. The expression of proteins was detected by western blots. The differential expression of RNAs was evaluated by RT-PCR and the interaction between P53 and drug was evaluated computationally using in-silico approach and in-vitro using ChIP assay. ResultsIn this study, we found that cryptolepine has more preferential cytotoxicity in TNBC than non-TNBC cells. Notably, our studies revealed the mechanism by which cryptolepine induces intrinsic apoptosis and inhibit migration, colony formation ability, induce cell cycle arrest by inducing conformational change in the mutant P53 thereby increasing its DNA binding ability, hence activating its tumor suppressing potential significantly. ConclusionOur study revealed that CRP significantly reduced the proliferation, migration and colony forming ability of TNBC cells lines. Moreover, it was revealed that CRP induces cell cycle arrest and apoptosis by activating mutant P53 and enhancing its DNA binding ability to induce its tumor suppressing ability.

Oleanolic acid derivative self-assembled aggregates based on heparin and chitosan for breast cancer therapy

Oleanolic acid is an active ingredient from natural products with anti-breast cancer activity. However, the poor solubility in water and low bioavailability have limited its effectiveness in clinic. To improve the anticancer activity of oleanolic acid, we synthesized a novel oleanolic quaternary ammonium (QDT), which, driven by electrostatic interactions, was introduced into heparin and coated with chitosan to obtain a QDT/heparin/chitosan nanoaggregate (QDT/HEP/CS NAs). QDT/HEP/CS NAs showed the negative zeta potential (−35.01 ± 4.38 mV), suitable mean particle size (150.45 ± 0.68 nm) with strip shape, and high drug loading (36 %). The coated chitosan had strong anti-leakage characteristics toward QDT under physiological conditions. More importantly, upon sustained release in tumor cells, QDT could significantly decrease the mitochondrial membrane potential and induce apoptosis of breast cancer cells. Further in vivo antitumor study on 4 T1 tumor-bearing mice confirmed the enhanced anticancer efficacy of QDT/HEP/CS NAs via upregulation of caspase-3, caspase-9 and cytochrome C, which was attributed to the high accumulation in tumor via the enhanced permeability and retention effect. Moreover, QDT/HEP/CS NAs significantly enhanced the biosafety and biocompatibility of QDT in vitro and in vivo. Collectively, the development of QDT/HEP/CS NAs with high antitumor activity, favorable biodistribution and good biocompatibility provided a safe, facile and promising strategy to improve the anti-cancer effect of traditional Chinese medicine ingredients.

Efficient synthesis of novel 1,10 phenanthroline-substituted imidazolium salts: Exploring their anticancer applications

This study reports a new series of 1,10-phenanthroline-substituted imidazolium salts (1a–f), examining their design, synthesis, structure and anticancer activities. The structures of these salts (1a–f) were characterized using 1H, 13C NMR, elemental analysis, mass spectrometry and Fourier transform infrared (FT-IR) spectroscopies. The salts' cytotoxic activities were tested against cancer cell lines, specifically MCF-7, MDA-MB-231 and non-tumorigenic MCF-10A mammary cells. The study compared the impact of aliphatic and benzylic groups in the salts’ structure on their anticancer activity. Screening results revealed that compound 1c, in particular, showed promising inhibitory activity against the growth of MDA-MB-231 breast cancer cells, with an IC50 value of 12.8 ± 1.2 μM, indicating its potential as a chemotherapeutic agent. Cell apoptosis analysis demonstrated a tendency for compound 1c to induce early apoptosis in breast cancer cells. The stability/aquation of compound 1c was investigated using 1H NMR spectroscopy and its binding modes with DNA were explored via UV–Vis spectroscopy. Additionally, the study investigated the interaction residues and docking scores of compound 1c and the reference drug doxorubicin against Bax and Bcl-2 proteins using molecular docking.

Structural regression modelling of peptide based drug delivery vectors for targeted anti-cancer therapy.

Drug resistance in cancer poses a serious challenge in finding an effective remedy for cancer patients, because of the multitude of contributing factors influencing this complex phenomenon. One way to counter this problem is using a more targeted and dose-limiting approach for drug delivery, rather than relying on conventional therapies that exhibit multiple pernicious side-effects. Stability and specificity have traditionally been the core issues of peptide-based delivery vectors. In this study, we employed a structural regression modelling approach in the design, synthesis and characterization of a series of peptides that belong to approximately same topological cluster, yet with different electrostatic signatures encoded as a result of their differential positioning of amino acids in a given sequence. The peptides tagged with the fluorophore 5(6)-carboxyfluorescein, showed higher uptake in cancer cells with some of them colocalizing in the lysosomes. The peptides tagged with the anti-cancer drug methotrexate have displayed enhanced cytotoxicity and inducing apoptosis in triple-negative breast cancer cells. They also showed comparable uptake in side-population cells of lung cancer with stem-cell like properties. The most-optimized peptide showed accumulation in the tumor resulting in significant reduction of tumor size, compared to the untreated mice in in-vivo studies. Our results point to the following directives; (i) peptides can be design engineered for targeted delivery (ii) stereochemical engineering of peptide main chain can resist proteolytic enzymes and (iii) cellular penetration of peptides into cancer cells can be modulated by varying their electrostatic signatures.

Chimeric antigen receptor dendritic cells targeted delivery of a single tumoricidal factor for cancer immunotherapy

BackgroundChimeric antigen receptor (CAR)-T cells have been used to treat blood cancers by producing a wide variety of cytokines. However, they are not effective in treating solid cancers and can cause severe side-effects, including cytokine release syndrome. TNFα is a tumoricidal cytokine, but it markedly increases the protein levels of cIAP1 and cIAP2, the members of inhibitor of apoptosis protein (IAP) family of E3 ubiquitin ligase that limits caspase-induced apoptosis. Degradation of IAP proteins by an IAP antagonist does not effectively kill cancer cells but enables TNFα to strongly induce cancer cell apoptosis. It would be a promising approach to treat cancers by targeted delivery of TNFα through an inactive adoptive cell in combination with an IAP antagonist.MethodsHuman dendritic cells (DCs) were engineered to express a single tumoricidal factor, TNFα, and a membrane-anchored Mucin1 antibody scFv, named Mucin 1 directed DCs expressing TNFα (M-DCsTNF). The efficacy of M-DCsTNF in recognizing and treating breast cancer was tested in vitro and in vivo.ResultsMucin1 was highly expressed on the surface of a wide range of human breast cancer cell lines. M-DCsTNF directly associated with MDA-MB-231 cells in the bone of NSG mice. M-DCsTNF plus an IAP antagonist, SM-164, but neither alone, markedly induce MDA-MB-231 breast cancer cell apoptosis, which was blocked by TNF antibody. Importantly, M-DCsTNF combined with SM-164, but not SM-164 alone, inhibited the growth of patient-derived breast cancer in NSG mice.ConclusionAn adoptive cell targeting delivery of TNFα combined with an IAP antagonist is a novel effective approach to treat breast cancer and could be expanded to treat other solid cancers. Unlike CAR-T cell, this novel adoptive cell is not activated to produce a wide variety of cytokines, except for additional overexpressed TNF, and thus could avoid the severe side effects such as cytokine release syndrome.

Comprehensive pancancer analysis reveals that LPCAT1 is a novel predictive biomarker for prognosis and immunotherapy response.

Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is a crucial enzyme involved in phospholipid metabolism and is essential for maintaining the structure and functionality of biofilms. However, a comprehensive examination of the role of LPCAT1 across various cancer types is lacking. Multiple public databases have been utilized to examine LPCAT1 expression, genetic alterations, methylation, prognosis, biological function, and its relationship with antitumor immunity in different cancer types. The function of LPCAT1 in glioma, breast cancer and liver cancer cells was further verified using in vitro experiments. Our research indicated that LPCAT1 is upregulated in various cancers and is accompanied by a wide range of amplification mutations. Higher LPCAT1 expression was associated with poorer prognosis across multiple cancers. Further in vitro experiments demonstrated that interfering with LPCAT1 expression increased apoptosis in glioma, breast cancer and liver cancer cells and concurrently suppressed their proliferation and migration. Functional enrichment analysis revealed that LPCAT1-associated genes were primarily enriched in immune and cancer progression pathways, such as the JAK/STAT, MYC, and EMT, etc. Moreover, LPCAT1 expression was closely associated with immune cell infiltration and immune checkpoint-related gene expression. Interestingly, LPCAT1 expression levels were generally higher in patients in the immunotherapy response group. The combination of LPCAT1 and PDL1 serves as an effective predictor of immunotherapy response. In conclusion, LPCAT1 is involved in immune regulation and tumor progression and holds promise as a biomarker for predicting patient outcomes and immunotherapy efficacy.

N6-methyladenosine modification of linc-OIP5 confers paclitaxel resistance in breast cancer through a DDX5-dependent mechanism

Chemoresistance is a significant obstacle in the treatment of breast cancer (BC). Due to its diverse composition, the causes of chemoresistance in BC are complex and have not been completely understood. In this article, we explored the mechanism of N6-methyladenosine (m6A)-modified long intervening noncoding RNA (linc)-OIP5 in BC chemoresistance. We successfully constructed drug-resistant cell lines MCF-7/P and MDA-MB-231/P by exposing parental MDA-MB-231 and MCF-7 cells to escalating doses of paclitaxel (PTX) and revealed multiple m6A methylation modification sites on linc-OIP5 according to the predictive analysis of the SRAMP database. Linc-OIP5 expression and m6A modification were up-regulated in PTX-resistant BC cells. Inhibition of m6A modification or linc-OIP5 knockdown facilitated PTX-resistant and parental BC cell apoptosis and repressed proliferation and migration. Mechanistically, linc-OIP5 bound to TRIM5 and reduced the ubiquitination of DDX5, thus stabilizing the DDX5 protein. Additionally, DDX5 overexpression partly abrogated the suppressing effects of inhibited m6A modification or si-linc-OIP5 on cell proliferation, migration and PTX resistance. These findings indicate that m6A-modified linc-OIP5 reduced DDX5 ubiquitination and enhanced DDX5 stability by binding to TRIM5, thereby promoting BC cell proliferation, migration and PTX resistance, and inhibiting apoptosis.

A polylysine/hyaluronan-based core-shell nanoparticle triggers drug delivery by ATP/hyaluronidase dual stimuli for inducing apoptosis of breast cancer cells

The limitations of self-assembled polymeric nanoparticles for cancer therapy, including instability in the bloodstream, non-specific targeting of cancer cells, and unregulated intracellular drug delivery, were effectively addressed by the development of core-shell SNX@PLL-FPBA/mHA NPs. The core was SNX@PLL-FPBA NPs prepared from polylysine conjugated 3-fluoro-4-carboxyphenylboronic acid (PLL-FPBA) self-assembly and SNX encapsulation, while the shell was methacrylate-modified hyaluronic acid (mHA) adhering to the core by electrostatic interactions and subsequently stabilized by photo-crosslinking, without the use of any organic solvent. SNX@PLL-FPBA/mHA NPs exhibited good stability in varying ionic strengths (0–0.30 M NaCl), pH levels (6.8 and 7.4), and plasma environments mimicking the blood, ensuring their efficacy in systemic circulation. The drug delivery from the nanoparticles was highly sensitive to ATP/Hyals stimuli (82 % within 48 h), closely mimicking the intracellular environment of breast cancer cells. The nanoparticles demonstrated good hemocompatibility and non-toxicity towards human skin fibroblasts. Efficient internalization of SNX@PLL-FPBA/mHA NPs by MCF-7 and MDA-MB-231 breast cancer cells was observed by CLSM and flow cytometry. The intracellular ATP/Hyals stimuli triggered the rapid drug delivery and induced cellular apoptosis. Thus, SNX@PLL-FPBA/mHA NPs were a promising drug nanocarrier for breast cancer therapy, offering improved stability, targeted delivery, and controlled drug release to enhance treatment outcomes.

Cynaropicrin, a sesquiterpene lactone, triggers apoptotic cell death in triple negative breast cancer cells.

Breast cancer is the most common cancer in the world. Cynaropicrin is a natural sesquiterpene lactone with potential anticancer effects. The present study was conducted to evaluate the effect of cynaropicrin on proliferation and apoptosis in breast cancer cells. MDA-MB-231 and MCF-7 cell lines were treated with increasing concentrations of cynaropicrin. The viability of both cell lines was measured using MTT assay. Flowcytometry was used to detect apoptotic cells. The expression levels of apoptosis-related genes were determined using quantitative polymerase chain reaction. The protein expression of apoptosis markers was determined by western blotting. Cynaropicrin significantly diminished the proliferation of MDA-MB-231 and MCF-7 cell lines in a dose-dependent manner. Flowcytometry data uncovered that cynaropicrin augmented early and late apoptosis in MDA-MB-231 cells. Real time-PCR and western blotting results also confirmed the upregulation of pro-apoptotic Bax, caspase-3, -8, and 9 as well as downregulated level of anti-apoptotic marker Bcl-2. Cynaropicrin also remarkably increased the activity of caspase-3, -8, and 9 in MDA-MB-231 cells. However, cynaropicrin neither promoted apoptosis in MCF-7 cells nor altered the expression levels and activity of above mentioned apoptotic markers. The present data indicated anti-proliferative properties of cynaropicrin against breast cancer and highlighted apoptosis-inducing effects of this sesquiterpene on triple negative breast cancer (TNBC) cells. These data may suggest cynaropicrin as a potential anti-TNBC agent to tackle therapy resistance in this type of breast cancer.

Innovative approach against cancer: Thymoquinone-loaded PHEMA-based magnetic nanoparticles and their effects on MCF-7 breast cancer

Breast cancer is most common cancer among women in the World. Thymoquinone (TQ) exhibits a wide range of biological activities such as anticancer, antidiabetic, antimicrobial, analgesic, antioxidant, and anti-inflammatory effects. However, its effectiveness in cancer treatment is hindered by its poor bioavailability, attributed to its limited solubility in water. Hence, novel strategies are required to enhance the bioavailability of TQ, which possesses remarkable anticancer characteristics. The aim of this study is to prepare pHEMA-based magnetic nanoparticles carrying TQ (TQ-MNPs) to improve bioavailability, and therapeutic efficacy against breast cancer. For this purpose, TQ-MNPs were synthesized and characterized with Fourier transform infrared spectrophotometer (FTIR), scanning electron microscopy (SEM), dynamic light scattering (DLS), magnetic field using a vibrating sample magnetometer (VSM). The loading capabilities of synthesized magentic nanostructures were evaluated, and release investigations were conducted under experimental conditions that mimic the cellular environment. The findings of the studies indicated that the TQ carrying capacity of MNPs was deemed satisfactory, and the release efficiency was adequate. MNPs and TQ-MNPs showed biocompatibility against HDFa cells. TQ-MNPs showed stronger anti-proliferative activity against MCF-7 breast cancer cells compared to free TQ (p < 0.05). TQ-MNPs induced apoptosis in MCF-7 breast cancer cells.

USP53 Affects the Proliferation and Apoptosis of Breast Cancer Cells by Regulating the Ubiquitination Level of ZMYND11

Breast cancer is the most common female malignancy worldwide. Ubiquitin-specific peptidase 53 (USP53) has been shown to exert cancer-suppressing functions in several solid tumors, but its role and the underlying mechanism in breast cancer has not been clearly elucidated. Therefore, we have carried out a series of detailed studies on this matter at the levels of bioinformatics, clinical tissue, cell function and animal model. We found that USP53 expression was downregulated in breast cancer specimens and was negatively correlated with the clinical stages. Gain- and loss-of-function experiments demonstrated USP53 inhibited proliferation, clonogenesis, cell cycle and xenograft growth, as well as induced apoptosis and mitochondrial damage of breast cancer cells. Co-immunoprecipitation data suggested that USP53 interacted with zinc finger MYND-type containing 11 (ZMYND11), and catalyzed its deubiquitination and stabilization. The 33–50 amino acid Cys-box domain was key for USP53 enzyme activity, but not essential for its binding with ZMYND11. The rescue experiments revealed that the anti-tumor role of USP53 in breast cancer cells was at least partially mediated by ZMYND11. Both USP53 and ZMYND11 were prognostic protective factors for breast cancer. USP53-ZMYND11 axis may be a good potential biomarker or therapeutic target for breast cancer, which can provide novel insights into the diagnosis, treatment and prognosis.

Role of the P2X7 receptor in breast cancer progression.

Breast cancer is a common malignant tumor, whose incidence is increasing year by year, and it has become the malignant tumor with the highest incidence rate in women. Purine ligand-gated ion channel 7 receptor (P2X7R) is a cation channel receptor with Adenosine triphosphate ( ATP) as a ligand, which is widely distributed in cells and tissues, and is closely related to tumorigenesis and progression. P2X7R plays an important role in cancer by interacting with ATP. Studies have shown that P2X7R is up-regulated in breast cancer and can promote tumor invasion and metastasis by activating the protein kinase B (AKT) signaling pathway, promoting epithelial-mesenchymal transition (EMT), controlling the generation of extracellular vesicle (EV), and regulating the expression of the inflammatory protein cyclooxygenase 2 (COX-2). Furthermore, P2X7R was proven to play an essential role in the proliferation and apoptosis of breast cancer cells. Recently, inhibitors targeting P2X7R have been found to inhibit the progression of breast cancer. Natural P2X7R antagonists, such as rhodopsin, and the isoquinoline alkaloid berberine, have also been shown to be effective in inhibiting breast cancer progression. In this article, we review the research progress of P2X7R and breast cancer intending to provide new targets and directions for breast cancer treatment.

Preliminary study on cytotoxicity of selegiline on different cancer cell lines: exploration of the induction of ROS-independent apoptosis in breast cancer cells.

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

Spatially Localized Entropy-Driven Evolution of Nucleic Acid-Based Constitutional Dynamic Networks for Intracellular Imaging and Spatiotemporal Programmable Gene Therapy.

The primer-guided entropy-driven high-throughput evolution of the DNA-based constitutional dynamic network, CDN, is introduced. The entropy gain associated with the process provides a catalytic principle for the amplified emergence of the CDN. The concept is applied to develop a programmable, spatially localized DNA circuit for effective in vitro and in vivo theranostic, gene-regulated treatment of cancer cells. The localized circuit consists of a DNA tetrahedron core modified at its corners with four tethers that include encoded base sequences exhibiting the capacity to emerge and assemble into a [2 × 2] CDN. Two of the tethers are caged by a pair of siRNA subunits, blocking the circuit into a mute, dynamically inactive configuration. In the presence of miRNA-21 as primer, the siRNA subunits are displaced, resulting in amplified release of the siRNAs silencing the HIF-1α mRNA and fast dynamic reconfiguration of the tethers into a CDN. The resulting CDN is, however, engineered to be dynamically reconfigured by miRNA-155 into an equilibrated mixture enriched with a DNAzyme component, catalyzing the cleavage of EGR-1 mRNA. The DNA tetrahedron nanostructure stimulates enhanced permeation into cancer cells. The miRNA-triggered entropy-driven reconfiguration of the spatially localized circuit leads to the programmable, cooperative bis-gene-silencing of HIF-1α and EGR-1 mRNAs, resulting in the effective and selective apoptosis of breast cancer cells and effective inhibition of tumors in tumor bearing mice.

Numerical investigation on flow-induced wall shear stress variation of metastatic cancer cells in lymphatics with elastic valves

Hematogenous metastasis occurs when cancer cells detach from the extracellular matrix in the primary tumor into the bloodstream or lymphatic system. Elucidating the response of metastatic tumor cells in suspension to the flow conditions in lymphatics with valves from a mechanical/fluidic perspective is necessary. A physiologically relevant computational model of a lymphatic vessel with valves was constructed using fully coupled fluid–cell–vessel interactions to investigate the effects of lymphatic vessel contractility, valve properties, and cell size and stiffness on the variations in magnitude and gradient of the flow-induced wall shear stress (WSS) experienced by suspended tumor cells. Results indicated that the maximum WSSmax increased with the increments in cell diameter, vessel contraction amplitude, and valve stiffness. The decrease in vessel contraction period and valve aspect ratio also increased the maximum WSSmax. The influence of the properties of the valve on the WSS was more significant among the factors mentioned above. The maximum WSSmax acting on the cancer cell when the cell reversed the direction of its motion in the valve region increased by 0.5–1.4 times that before the cell entered the valve region. The maximum change in WSS was in the range of 0.004–0.028 Pa/µm depending on the factors studied. They slightly exceeded the values associated with breast cancer cell apoptosis. The results of this study provide biofluid mechanics-based support for mechanobiological research on the metastasis of metastatic cancer cells in suspension within the lymphatics.