Proliferation Of MCF-7 Breast Cancer Cells Research Articles

Low expression of KLRB1 predicts poor survival outcomes and is associated with immune infiltration in breast cancer.

KLRB1 is downregulated in various cancer types. Nevertheless, the specific involvement of KLRB1 in the context of breast cancer (BRCA) has not been fully elucidated. This research aimed to explore its clinical value in BRCA. A dataset comprising 1,109 BRCA samples and 113 healthy samples was retrieved from The Cancer Genome Atlas (TCGA) database to establish the association between KLRB1 expression and pan-cancer. Subsequently, an analysis was executed to explore the link between KLRB1 and BRCA. T-tests and Chi-squared tests were conducted to assess the expression of KLRB1 and its clinical implications in BRCA. The prognosis-predictive value of KLRB1 in BRCA was assessed using the Kaplan-Meier method and Cox regression analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses screened biological pathways to analyze the association between the immune infiltration level and KLRB1 expression in BRCA. Lastly, the conclusion was validated through quantitative polymerase chain reaction (qPCR), immunohistochemistry (IHC), and Cell Counting Kit-8 (CCK8) assays. KLRB1 exhibited low expression in patients with BRCA. Furthermore, KLRB1 demonstrated strong diagnostic potential, as indicated by an area under curve (AUC) of 0.712. Kaplan-Meier survival and Cox regression analyses indicated that attenuated expression of KLRB1 was independently linked to unfavorable clinical outcomes. GO and KEGG enrichment analyses were performed on the top 10 genes that exhibited positive and negative correlations with KLRB1. Analysis of genes positively correlated with KLRB1 revealed associations with signaling receptor activator activity, lymphocyte proliferation, mononuclear cell proliferation, leukocyte proliferation, receptor-ligand activity, immunoglobulin binding, and hematopoietic cell lineage signaling pathway. KLRB1 expression exhibited significant correlations with all immune cells. Furthermore, qPCR and IHC outcomes demonstrated that KLRB1 was significantly downregulated in BRCA tissues. CCK8 findings showed a decrease in the proliferation of BRCA MCF7 cells upon knockout of KLRB1. This research investigated the mechanism and potential therapeutic target of the KLRB1 gene in BRCA. By analyzing the expression and function of the KLRB1 gene, the study aims to find its significant role in the onset and progression of BRCA. This research endeavors to offer novel strategies and approaches for treating BRCA.

The Fat and the Furious: MCF-7 Breast Cancer Cell Proliferation Trends in Fat Grafting Lipoaspirate Conditioned Media

The Fat and the Furious: MCF-7 Breast Cancer Cell Proliferation Trends in Fat Grafting Lipoaspirate Conditioned Media

Mesenchymal Stem Cell-Derived Extracellular Vesicles Increase Human MCF7 Breast Cancer Cell Proliferation associated with OCT4 Expression and ALDH Activity.

The aim of this study was to investigate the effect of mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) on the human MCF7 breast cancer cell proliferation that have been considered to contain limited CSC population and its association with the expression of OCT4 and ALDH1 stemness markers. EVs were successfully isolated from the conditioned medium of umbilical cord MSCs using size exclusion chromatography. The isolated EV fraction was verified under a transmission electron microscope (TEM). Five and ten percent (v/v) concentration of MSC-EVs were then co-cultured with MCF7 cells. To investigate MSC-EV uptake by MCF7 cells, we performed confocal microscopy analysis. Subsequently, the proliferation of co-cultured MCF7 cells was determined using trypan blue exclusion assay, while their mRNA and protein expression of OCT4 as well as ALDH activity as the marker of stemness properties were analyzed using quantitative reverse transcription polymerase chain reaction, Western Blot, and Aldefluor™ assays, respectively. MSC-EVs were detected as round-shaped, ~100 nm sized particles under TEM. We also demonstrate that MSC-EVs can be internalized by MCF7 cells. Notably, MSC-EVs of 5% concentration increased OCT4 mRNA expression and ALDH1 activity in MCF7 cells. At 10% concentration, MSC-EVs reduced the OCT4 expression and ALDH1 activity. MSC-derived EVs modulate the stemness of MCF7 cells, either OCT4 expression or ALDH1 activity, in a concentration dependent manner along with the increase of cell proliferation.

Synthesis and research of the pharmacophoric properties of some N-(dimethylphenyl) hydrazinecarbotioamide

The present study was focused on the synthesis of some N-(dimethylphenyl)hydrazine carbothioamides 1-4, that contain the following N-substituents: 2,4-dimethylphenyl; 2,5-dimethylphenyl; 2,6-dimethylphenyl; 3,4-dimethylphenyl, to increase lipophilicity and N-(dimethylphenyl)-2-(pyridin-2-ylmethylidene)hydrazinecarbothioamides 5-8, analogous of Triapine. The structural formula of the compounds was characterized by means of spectroscopy: FT-IR, 1H-, and 13CRMN, and the molecular structure, for the first time, by means of X-ray diffraction. The study of antioxidant activity has shown that all compounds 1-8 are powerful antioxidants. N-(dimethylphenyl)-2-(pyridin2-ylmethylidene)hydrazinecarbothioamides 5-8 were tested as inhibitors of MCF-7 (breast cancer) cell proliferation. It was found that all the compounds exhibit activity comparable to that of Doxorubicin, among them the compound N-(2,5-dimethylphenyl)-2-(pyridin-2-ylmethylidene)hydrazinecarbothioamide 6, with IC50=0.8 μM/L, demonstrated the highest activity.

Insulin-like growth factor binding protein-3 induces senescence by inhibiting telomerase activity in MCF-7 breast cancer cells

Insulin-like growth factor binding protein-3 (IGFBP-3) has been known to inhibit cell proliferation and exert tumor-suppressing effects depending on the cell type. In this study, we aimed to show that IGFBP-3 induces cellular senescence via suppression of the telomerase activity, thereby inhibiting MCF-7 breast cancer cell proliferation. We found that the induction of IGFBP-3 in MCF-7 cells enhanced the loss of cell viability. Flow cytometry revealed a higher percentage of non-cycling cells among IGFBP-3-expressing cells than among controls. IGFBP-3 induction also resulted in morphological alterations, such as a flattened cytoplasm and increased granularity, suggesting that IGFBP-3 induces a senescence-like phenotype. The percentage of IGFBP-3 expressing cells with senescence-associated β-galactosidase activity was 3.4 times higher than control cells. Telomeric repeat amplification and real-time PCR showed that IGFBP-3 decreased telomerase activity by reducing the levels of the RNA component (hTR) and catalytic protein component with reverse transcriptase activity (hTERT) of telomerase in a dose-dependent manner. These results suggest that IGFBP-3 is a negative regulator of MCF-7 breast cancer cell growth by inducing senescence through telomerase suppression.

Beta-sitosterol from sablo ( Acalypha wilkesiana Muell. Arg.) leaves induce apoptosis in MCF-7 Breast cancer cell lines

One of the most common malignancy breast cancer is highly prevalent among women. Based on the natural ingredients it contains, the plants of sablo have the potential to be employed as an anticancer therapeutic. Numerous studies have demonstrated that the chance of developing breast cancer rises with age. Additionally, the prevalence of breast cancer varies according to the different types of biased traditional Chinese medicine constitution, and the Qi-depressed constitution is highly concomitant and increases the prevalence of breast cancer. As a result, the Qi-depressed constitution is a separate risk factor for breast cancer. Previous studies have shown that the ethanol extract of Acalypha wilkesiana and its components have potential as anticancer agent against MCF-7. In the current study, using resazurin assays and flow cytometry, beta-sitosterol extracted from Acalypha wilkesiana was examined in MCF-7 human breast cancer cell lines. Resazurin experiments demonstrated its capacity to inhibit cell proliferation and trigger apoptosis, and flow cytometry was utilized to examine this capacity. Beta-sitosterol inhibits MCF-7 breast cancer cell proliferation and has an apoptotic activity that is proportional to the dose. The results of this study imply that beta-sitosterol may be used to treat cancer.

A novel platform for the production of autologous human antibodies.

At Research Genetic Cancer Centre, we have developed a novel method for the production of human monoclonal antibodies against a specific antigen of our choice (c-met) using isolated human blood cells. By mimicking nature, dendritic, CD4 and CD19 cells from healthy volunteers were driven towards Th2 immunity. Cell activation was succeeded by a cytokine cocktail, and IgG production was promoted by IgG class switching factors. IgG secretion was determined using both enzyme linked immunosorbent assay (ELISA) and Western blot as well as immunoglobulin heavy chain gamma polypeptide gene expression. Secreted antibody was further purified by affinity column chromatography against c-met peptide. Anti-c-met activity was determined using the purified antibody as primary antibody for c-met detection by ELISA, Western blot and flow cytometry. Finally, anti-c-met antibody efficiency was determined by MCF-7 viability assay. Plasma cell formation and IgG secretion took place after 6 days of culture. Plasma cells produced anti-c-met IgG antibody that significantly decreased MCF-7 breast cancer cell proliferation. To our knowledge, this is the first platform of its kind, generating fully human antibodies-on-demand using patient's own cells, bringing personalized, targeted therapy for cancer one step closer.

Detoxification of the mycoestrogen zearalenone by Bacillus licheniformis spore CotA laccase and application of immobilized laccase in contaminated corn meal

Zearalenone (ZEN) is an estrogen-like mycotoxin posing a great threat to human and animal health. The present study showed that the induction of spore CotA laccase production of Bacillus licheniformis by ions Mn2+ and Cu2+ promoted the ZEN-degrading ability of the strain. The spore CotA laccase heterologously expressed in Escherichia coli was capable of directly oxidizing ZEN with Km, Kcat and Vmax values of 90.43 μg mL−1, 0.11s−1 and 35.48 μg min−1 mg−1, respectively. The use of 2, 2′-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), acetosyringone, ferulic acid, caffeic acid and methyl syringate as redox mediators could enhance ZEN degradation by CotA laccase. The human breast cancer MCF-7 cell proliferation assay showed that CotA laccase and CotA laccase-mediator systems eliminated the estrogenicity of ZEN. Immobilized CotA laccase onto chitosan microspheres exhibited higher thermal stability over free CotA laccase, maintaining about 87% of its initial activity after heat treatment at 80 °C for 30 min. The removal rate of ZEN in corn meal by free and immobilized CotA laccase was 70% and 90%, respectively. Meanwhile, immobilized enzyme could achieve a 54% ZEN degradation in corn meal after three consecutive cycles. Thus, CotA laccase could be a promising biocatalyst for detoxification of ZEN in corn meal.

In vitro studies on inhibition capability of fungal-sourced bassiatin versus tamoxifen against ERα, EGFR and VEGFR on breast cancer cells.

Bassiatin which is produced by some fungi, is morpholine-based depsipeptide. Recent studies show that bassiatin inhibits MCF-7 breast cancer cell proliferation with its anti-oestrogenic effect. In this study, bassiatin's inhibition versus Tamoxifen was examined by comparing the effects on epidermal growth factor receptor and vascular endothelial growth factor receptor in addition to oestrogen receptor on breast cells. For this purpose, 15 concentrations of bassiatin, tamoxifen and combination of both were treated in terms of cytotoxicity on MCF-7, MDA-MB-231, SK-BR-3 and SVCT cell lines. For cell cycle analyses, MCF-7 and SVCT cell lines were incubated with 37.5 μM bassiatin, tamoxifen and combined substance for 24 h and 48 h. After treatment, cell distribution in each phase of the cell cycle was measured with flow cytometer. Furthermore, each interaction related to receptors were investigated with immunoassay ELISA kits. As a result, bassiatin-induced MCF-7 cell cycle arrest was shown in G0/G1 and G2/M phases at the presence of bassiatin. It was also found that bassiatin is more effective at all examined receptors on breast cancer cells than tamoxifen. These results show that bassiatin can be used effectively in breast cancer treatment as a new anticancer agent because of its multiple inhibition effects.

Ppm1b Negatively Regulates 3-Bromopyruvate Induced Necroptosis in Breast Cancer Cells.

Up to 30% of breast cancer mortality is caused by cancer relapse despite primary clinical treatments due to distant metastases. Further research focusing on breast cancer mechanisms are needed for deeper understanding of disease prognosis. 3-bromopyruvate (3-BP), a glycolysis inhibitor, has been studied as one of the antitumor agents in recent years. In this report, we want to investigate the form of cell death induced by 3-BP and demonstrate the inhibitory effect of 3-BP on breast cancer cell proliferation and its mechanism in vivo and in vitro. We found that 3-BP could inhibit MDA-MB-231 and MCF-7 breast cancer cell proliferation, through energy metabolism inhibition. Further, necroptosis characters in MDA-MB-231 cells after 3-BP treatment were observed, which could be negatively regulated through Ppm1b by dephosphorylation of RIP3. In addition, 3-BP treatment in an MDA-MB-231 cell-transplanted mouse model showed a significant antitumor effect, which correlated with necroptosis-related protein Ppm1b. The findings demonstrate the potential for 3-BP in the treatment of breast cancer, providing impetus for further clinical studies.

Thermally drawn biodegradable fibers with tailored topography for biomedical applications.

There is a growing demand for polymer fiber scaffolds for biomedical applications and tissue engineering. Biodegradable polymers such as polycaprolactone have attracted particular attention due to their applicability to tissue engineering and optical neural interfacing. Here we report on a scalable and inexpensive fiber fabrication technique, which enables the drawing of PCL fibers in a single process without the use of auxiliary cladding. We demonstrate the possibility of drawing PCL fibers of different geometries and cross-sections, including solid-core, hollow-core, and grooved fibers. The solid-core fibers of different geometries are shown to support cell growth, through successful MCF-7 breast cancer cell attachment and proliferation. We also show that the hollow-core fibers exhibit a relatively stable optical propagation loss after submersion into a biological fluid for up to 21 days with potential to be used as waveguides in optical neural interfacing. The capacity to tailor the surface morphology of biodegradable PCL fibers and their non-cytotoxicity make the proposed approach an attractive platform for biomedical applications and tissue engineering.

Preparation, characterization and evaluation of cytotoxic activity of Tamoxifen bound liposomes against breast cancer cell line

The goal of this study was to determine whether neutrally or positively charged liposomes encapsulated with tamoxifen could inhibit the proliferation of human breast cancer MCF-7 cell proliferation compared to free tamoxifen by estimating the potential effects of these complexes on the cell death of human breast carcinoma (MCF-7) cell lines. The formulated tamoxifen liposomal conjugate was characterized by analytical techniques to determine its size, size-distribution, thermotropic changes and conformational changes along with possible cytotoxicity towards MCF-7 (breast cancer cell line) in Vitro. The mean particle diameter was estimated to be 64.70±49.75 nm, 73.72±23.8 nm and 119±54.7 nm for blank liposomes, neutral and positively charged liposomes bound tamoxifen, respectively. As tamoxifen is introduced into positive liposomes, it results in noticeable broadening and shift to lower temperature at 135 C compared to the main characteristic endothermic peak (Tm) of pure liposomes that exists at 140C, while the introduction of tamoxifen into neutral liposomes contributes to the disappearance of the main endothermic peak of pure liposomes. FTIR analysis revealed structure changes in vesicles after tamoxifen was incorporated into liposomes. The IC50 value for tamoxifen in the cytotoxic assay with MCF-7 treated cells was 0.34 μg/ml, while tamoxifen-loaded neutrally or positively charged liposomes showed an increase of IC50 value to 119.62 and 101.23 µg /ml, respectively. Current data suggests a new treatment regimen in where free tamoxifen is substituted with liposomal tamoxifen to improve anticancer activity against MCF-7 cancer cell lines.

Carvacrol Promotes Cell Cycle Arrest and Apoptosis through PI3K/AKT Signaling Pathway in MCF-7 Breast Cancer Cells.

To examine the role of carvacrol in modulating PI3K/AKT signaling involved in human breast cancer pathogenesis using in vitro experimental model MCF-7 cells. MTT and lactate dehydrogenase assays were performed with cells treated with different doses of carvacrol (0-250 p mol/L) at different time points (24 and 48 h). The nuclear morphology was assessed in MCF-7 cells with propidium iodide (PI) and acridine orange/ethidium bromide (AO/EB) staining and analyzed by fluorescence microscopy. Events like cell cycle arrest, apoptosis was observed by flow cytometric analysis and expressions of p-Rb, cyclin D1, cyclin-dependent kinase 4 (CDK4), CDK6, Bax, Bcl-2, PI3K/p-AKT was analyzed by immunoblot. Carvacrol significantly reduced cell viability with the half maximal inhibitory concentration value of 200 µmol/L at 24 and 48 h (P<0.05). importantly, there was a significant increase in the accumulation of the G0/G1 phase upon treatment with carvacrol in MCF-7 cells (P<0.05 or P<0.01). A remarkable decrease in protein expressions of p-Rb, cyclin D1, CDK4 and CDK6 denotes cell cycle arrest (P<0.05 or P<0.01). In addition, carvacrol treatment significantly inhibited PI3K/p-AKT protein expressions leading to induction of apoptosis mediated by decreased Bcl2 and increased Bax protein expressions. Further, Annexin V/PI staining by FACS analysis, dual staining by AO/EB and PI staining studies suggests induction of apoptosis by carvacrol through PI3K/Akt signaling pathway in MCF-7 cells. Carvacrol significantly inhibited the breast cancer MCF-7 cell proliferation and induced apoptosis via suppressing PI3/AKT signaling pathway.

Retinoic Acid-Related Orphan Receptor alpha 1 (RORα1) Induction of AKR1C3 Promotes MCF-7 Breast Cancer Cell Proliferation and Tamoxifen-Resistance which is Suppressed by Melatonin

The retinoic acid-related orphan receptors alpha (RORa) are members of the steroid/thyroid nuclear receptor super-family and core components of the circadian timing system. In the present study, we continue to investigate the role of RORas in human breast cancer. Assays using the RORa response element (RORE)-tk-luciferase reporter demonstrate the functionality of the RORa1 in MCF-7 breast cancer cells and that over-expression of RORa1 stimulates MCF-7 human breast cancer cell proliferation. Genomic analysis revealed that RORα1 over-expression regulated the transcription of numerous genes in MCF-7 breast cancer cells including increasing the expression of connexin 43 (CX43), aldo-keto reductases 1C1 (AKR1C1), and AKR1C3. Furthermore, administration of the pineal hormone melatonin represses RORa1 induction of CX43, AKR1C1, and AKR1C3 in MCF-7 cells. AKR1C3 has been reported to impact in intra-tumoral production of androgens and estrogens and thus, might promote Tamoxifen resistance in breast cancer. Over-expression of RORa1 and subsequently AKR1C3 does promote Tamoxifen resistance, which can be inhibited by melatonin administration.

Identification of hub genes and potential molecular mechanisms of chickpea isoflavones on MCF-7 breast cancer cells by integrated bioinformatics analysis.

Chickpea isoflavones have been demonstrated to play an inhibitory role in breast cancer cells. In this study, we aimed to explore the mechanism of chickpea isoflavones inhibiting the formation and development of breast carcinoma through the integration of wet and dry experiments. Chickpea isoflavones were added to the MCF-7 cells for 48 hours, and the subsequent morphological changes of cells were observed using an inverted microscope, while apoptosis was quantified by flow cytometry. The mRNA and LncRNA expression profiles were detected by RNA-sequencing (RNA-Seq) technology. The protein-protein interaction (PPI) network was constructed from the STRINGdb database. To identify the co-expressed long non-coding RNA and messenger RNA (lncRNA-mRNA) pairs, Pearson's correlation coefficients were calculated based on the expression value between every differentially expressed lncRNA and mRNA pair. The hub gene expression was verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and survival analysis results were provided by The Human Protein Atlas website. Microscopic observation and flow cytometry results confirmed that chickpea isoflavones with a final concentration of 32.8 µg/mL could cause apoptosis of the MCF-7 cells. Transcriptome results showed that a total of 1,094 mRNAs and 378 lncRNAs were differentially expressed in isoflavone-treated cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment revealed that inhibition of cell proliferation was mainly due to the up-regulation of genes in the apoptosis signaling pathway and the down-regulation of genes in mRNA splicing pathway. The co-expressed genes of the top 10 down-regulated lncRNAs were mainly heterogeneous nuclear ribonucleoproteins (HNRNP) family genes, which interacted with apoptosis-related genes through ubiquitin C (UBC). The abnormal expression of 11 hub genes (degree >10) of PPI networks were beneficial to improve the overall survival time of breast cancer patients. Our results reveal a potential mechanism for chickpea isoflavones to inhibit MCF-7 breast cancer cell proliferation and provide a reference for the development of new anti-cancer drugs used in breast cancer.

ER-mediated anti-tumor effects of shikonin on breast cancer

Estrogen receptor (ER) is expressed in most Breast cancer (BC) patients. G protein-coupled estrogen receptor (GPER), which is a membrane-bound estrogen receptor, is associated with the tumor development and progression in BC. Shikonin (SK) is a natural compound that is known to have anti-tumor effects. This study aims to assess the effects of shikonin on the cell proliferation, cell cycle and cell apoptosis of BC and whether the effects are related to ER/GPER signaling pathway. The results demonstrated that shikonin inhibited the cellular proliferation of MCF-7 BC cells via G0/G1 arrest and apoptosis in concentration-dependent manner. The anti-proliferative effect of SK on SK-BR-3 BC cells was associated with apoptosis. Both ERα and GPER were expressed in MCF-7 cells, while ERα were negative and GPER were positive in SK-BR-3 cells. Furthermore, shikonin downregulated the expression of ERα and GPER, and this effect was not affected by the estrogen environment. In addition, shikonin downregulated the EGFR and p-ERK expression in MCF-7 and SK-BR-3, which was also not affected by the estrogen environment. EGFR and p-ERK were still suppressed by co-treatment with the selective GPER against G1 or antagonist G15. In conclusion, these results suggest that shikonin shows anti-tumor effects on MCF-7 and SK-BR-3 cells. The effects seem to be associated with EGFR/p-ERK downregulation via ERα and GPER inhibition.

Inhibition of MCF-7 breast cancer cell proliferation by a synthetic peptide derived from the C-terminal sequence of Orai channel

Intracellular Ca2+ signals play many important cellular functions such as migration, proliferation and differentiation. Store-operated Ca2+ entry (SOCE) is a major route of Ca2+ entry in nonexcitable cells. The activation of SOCE requires engagement between stromal interaction molecule 1 (STIM1) molecules on the endoplasmic reticulum and Ca2+ release-activated Ca2+ (CRAC) channel Orais (Orai1-3) on the plasma membrane. Accumulating evidence indicates that SOCE plays critical roles in cancer cell proliferation, invasion and metastasis. Here, we used the synthetic intracellular peptides derived from the C-termini of Orai channels to treat the breast cancer cells. We have found that Orai3-CT peptide exhibits stronger binding to STIM1 than Orai1-CT, and Orai3-CT peptide acts in a dominant negative fashion, blocking the STIM1-Orai1 interaction and reducing the Ca2+ entry and proliferation of breast cancer cells.

Cytotoxic Effect of Paclitaxel and Lapatinib Co-Delivered in Polylactide-co-Poly(ethylene glycol) Micelles on HER-2-Negative Breast Cancer Cells.

To find better strategies to enhance the cytotoxic effect of paclitaxel (PTX) and lapatinib (LAP) against breast cancer cells, we analyzed the efficacy of a novel delivery system containing polylactide-co-poly(ethylene glycol) (PLA-PEG) filomicelles of over 100 nm in length and spherical micelles of approximately 20 nm in diameter. The 1H NMR measurements confirmed the incorporation of PTX and LAP into micelles. Analysis of the drug release mechanism revealed the diffusion-controlled release of LAP and anomalous transport of PTX. Drug content analysis in lyophilized micelles and micellar solution showed their good storage stability for at least 6 weeks. Blank micelles, LAP-loaded micelles and free LAP did not affect MCF-7 breast cancer cell proliferation, suggesting that the cytotoxicity of PTX-, PTX/LAP-loaded micelles, and the binary mixture of free PTX and LAP was solely caused by PTX. PTX/LAP-loaded micelles showed greater toxicity compared to the binary mixture of PTX and LAP after 48 h and 72 h. Only free PTX alone induced P-gp activity. This study showed the feasibility of using a LAP and PTX combination to overcome MDR in MCF-7 cells, particularly when co-loaded into micelles. We suggest that PTX/LAP micelles can be applicable not only for the therapy of HER-2-positive, but also HER-2-negative breast cancers.

Effects of carbendazim and astaxanthin co-treatment on the proliferation of MCF-7 breast cancer cells.

There has been a controversy in the oncology field about the use of antioxidants along with chemotherapeutics in cancer treatment. This study aimed to investigate the effects of a potent antioxidant (astaxanthin) co-treatment with a promising anti-cancer drug (carbendazim), which is in phase I clinical trials, on MCF-7 breast cancer cell proliferation. MCF-7 cells were treated with carbendazim, astaxanthin, or their combinations and incubated for 24h. After the incubation, each treatment group was evaluated for proliferation, cell cycle progression, and production of reactive oxygen species (ROS) using WST-1, flow cytometry, and CM-H2DCFDA, respectively. All tested carbendazim and astaxanthin combinations increased the anti-proliferative effect of Carb treatment alone and increased the G2/M phase cell cycle arrest compared to the DMSO-treated control. Astaxanthin, at all concentrations tested, reduced the elevated intracellular ROS levels induced by the carbendazim treatment. Our data suggest that astaxanthin and carbendazim co-treatment enhances the anti-proliferative effect of carbendazim as a single agent, while alleviating the carbendazim treatment-associated ROS production in MCF-7 cells. These findings may contribute to the current debate on the use of antioxidants along with anti-cancer drugs in cancer chemotherapy.

New Class of Selective Estrogen Receptor Degraders (SERDs): Expanding the Toolbox of PROTAC Degrons.

An effective endocrine therapy for breast cancer is to selectively and effectively degrade the estrogen receptor (ER). Up until now, there have been largely only two molecular scaffolds capable of doing this. In this study, we have developed new classes of scaffolds that possess selective estrogen receptor degrader (SERD) and ER antagonistic properties. These novel SERDs potently inhibit MCF-7 breast cancer cell proliferation and the expression of ER target genes, and their efficacy is comparable to Fulvestrant. Unlike Fulvestrant, the modular protein-targeted chimera (PROTAC)-type design of these novel SERDs should allow easy diversification into a library of analogs to further fine-tune their pharmacokinetic properties including oral availability. This work also expands the pool of currently available PROTAC-type scaffolds that could be beneficial for targeted degradation of various other therapeutically important proteins.