MCF-7 Breast Cancer Cells Research Articles

Recombinant Methioninase (rMETase) Synergistically Sensitizes Ivermectin-resistant MCF-7 Breast Cancer Cells 9.9 Fold to Low-dose Ivermectin.

Ivermectin is a widely-used anti-parasitic agent and has shown early promise as an anticancer agent. Recombinant methioninase (rMETase) is a methionine-depleting enzyme targeting the methionine addiction of cancer and has broad efficacy against all tested cancer types. However, the combination efficacy of ivermectin and rMETase on breast cancer cells remains unexplored. The present study aimed to determine the synergistic efficacy of ivermectin and rMETase on MCF-7 human breast cancer cells in vitro. The IC10 of ivermectin and IC50 of rMETase were determined on MCF-7 cells using the WST-8 reagent to measure cell viability in vitro. MCF-7 cells were treated with four groups: untreated control; ivermectin alone (4.89 μM, IC10); rMETase alone (2.75 U/ml, IC50); and a combination of ivermectin (4.89 μM) and rMETase (2.75 U/ml). Cell viability was assessed 72 hours after treatment with the WST-8 reagent. Treatment with ivermectin (4.89 μM) did not significantly reduce the viability of MCF-7 cells. rMETase (2.75 U/ml) alone significantly reduced MCF-7 cell viability compared to the control group. The combination of ivermectin and rMETase resulted in a significantly greater reduction in cell viability than either agent alone, including a 9.9-fold greater efficacy than ivermectin alone, demonstrating synergistic efficacy (p<0.05). The combination of ivermectin and rMETase had synergistic efficacy against MCF-7 breast cancer cells in vitro. The present findings suggest that the combination of ivermectin and rMETase is a promising strategy for breast cancer requiring further preclinical and clinical evaluation.

Identification of 8-(2-methyl phenyl)-9H-benzo[f]indeno[2,1-c]quinolin-9-one (C-5635020) as a novel and selective TGFβ RII kinase inhibitor for breast cancer therapy.

Transforming growth factor-beta (TGF-β) plays a pivotal role in breast development by modulating tissue composition during the developmental phase. The TGFβ type II receptor (TGFβ RII) is implicated in breast cancer and represents a valuable therapeutic target. Due to the off-target side effects of many existing TGFβI/TGFβ RII inhibitors, a more targeted approach to drug discovery is necessary. This study used computational modeling and molecular dynamics simulations to screen the ChemBridge small molecule library against TGFβ RII. This study employed high-throughput virtual screening, molecular dynamics simulations, and binding free energy calculations to identify potential inhibitors targeting TGF-β RII. MDA-MB 231 and MCF-7 breast cancer cells were used in anti-proliferative, tans-endothelial migration, and flow cytometric assays for in vitro validations. We identified 8-(2-methylphenyl)-9H-benzo[f]indeno[2,1-c]quinolin-9-one (C-5635020) as a potent and selective inhibitor. Protein-ligand modeling analysis revealed that C-5635020 targets the kinase domain of TGFβ RII with superior binding affinities compared to the standard drug, staurosporine. Computational results suggest that C-5635020 selectively binds and inhibits TGFβ RII activity, thereby controlling cell proliferation in breast cancer. In vitro, experiments corroborated these predictions, where C-5635020 inhibited TGFβ RII and p-Smad 2/3 positive population in MDAMB-231 and MCF-7cells. The compound dose-dependently inhibited cell proliferation, trans-endothelial migration, and increased apoptosis in both breast cancer cell lines. The strong binding affinity, stability, and favorable thermodynamics of C-5635020 with established in vitro efficacy highlight its potential as a lead compound for further preclinical and clinical developments for breast cancer treatment.

Docetaxel treatment together with CTLA-4 knockdown enhances reduction of cell viability and amplifies apoptosis stimulation of MCF-7 breast cancer cells.

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

Synthesis, Characterization, Docking Studies, and In-vitro Cytotoxic Activity of Some Novel 2, 3 Disubstituted Naphthalene 1,4 Dione Derivatives

Introduction: Many quinone derivatives as of now utilized for anticancer medications. Especially, 1,4-naphthoquinones are dynamic derivatives, and it was broadly utilized in unrefined substances in the drugs and agrochemicals industry. Materials and Methods: In this work, we planned and combined five different moieties into 2, 3 disubstituted naphthalene-1,4-dione molecules. Various spectral studies distinguished the synthetic designs of the produced compounds. The naphthoquinone derivatives were exposed to the primary molecular descriptor by Molinspiration programming, and all the descriptor values are within the specified value. Results and Discussion: Each of the five naphthoquinone derivatives was docked against the Topoisomerase II utilizing Auto Dock program 4.2.5. (PDB: 3L4K). The docking tells us that the studied compounds possess significant to moderate inhibition toward the targeted enzymes. Among the studied compounds, compound L3 showed the most elevated binding score (-10.66 kcal/mol with one H-bond) than the adriamycin (-9.58 kcal/mol with two H-bonds) and compound L2 (- 9.86 kcal/mol with two H-bonds). The derivatives were tried for in-vitro cytotoxicity studies against MCF - 7 by the SRB method. Among them, compounds L2 (28.42±3.1 μg/mL) and L3 (29.38±3.2 μg/mL) were the most significant ones when contrasted with the control Adriamycin (15.28±3.4 μg/mL). Conclusion: The current research indicates that the tested compounds show anticancer action against the MCF-7 breast cancer cell line. Thus, the study is an attempt to advance toward the identification of innovative anticancer drugs.

In Vitro Potentiation of Doxorubicin Cytotoxicity Utilizing Clarithromycin Loaded-PEGylated Liposomes.

Doxorubicin (DOX) is a potent chemotherapeutic agent for breast cancer, but its effectiveness is often diminished by resistance mechanisms, particularly through p-glycoprotein (P-gp) mediated drug efflux. Clarithromycin (CAM), a macrolide antibiotic, inhibits multiple metabolic pathways including CYP3A and P-gp, potentially countering DOX resistance. This study aimed to evaluate the potentiation of DOX and its effectiveness against the MCF-7 breast cancer cell line by encapsulating both DOX and CAM in PEGylated liposomes. PEGylated liposomes containing DOX and CAM were prepared using the thin film hydration method. The physicochemical properties of the liposomes, including average particle size, polydispersity index (PDI), and zeta potential, were characterized. Encapsulation efficiencies for CAM and DOX were assessed, and stability of the liposomes was evaluated over 9 days at room temperature. Cell viability was measured using an IC50 assay, and P-gp expression levels were determined by ELISA. The CAM/DOX-PEGylated liposomes exhibited optimal average particle size (238 ± 26.7 nm), PDI (0.29 ± 0.107), and zeta potential (-20.9 ± 2.17 mV). These liposomes maintained good stability regarding size and charge over 9 days. Encapsulation efficiencies were 81.05% for CAM and 78.13% for DOX. The IC50 value for CAM/DOX-PEGylated liposomes was 0.13 µM, representing a significant reduction compared to the physical mixture of CAM and DOX (0.25 µM) and free DOX (0.21 µM) against MCF-7 cells. ELISA analysis showed a reduction in P-gp expression of approximately 5% with CAM/DOX-PEGylated liposomes compared to 1.61% with free DOX. The results indicate that CAM encapsulated in PEGylated liposomes enhances the effectiveness of DOX against breast cancer cells, likely through the inhibition of p-glycoprotein. This approach may offer a promising strategy to overcome DOX resistance and improve chemotherapy outcomes.

Palbociclib-letrozole loaded solid self-nano emulsifying drug delivery system for oral treatment of breast cancer: In-vitro and In-vivo characterization

The current research aimed to formulate a self-nanoemulsifying drug delivery system (SNEDDS) co-loaded with palbociclib (PCB) and letrozole (LTZ) to enhance anticancer efficacy by improving oral solubility and bioavailability. Liquid PCB-loaded SNEDDS (L-PSNE-1 to L-PSNE-9) were optimized for high % transmittance, % cumulative drug release (%CDR), and low self-emulsification time using a 32 full factorial design. LTZ was incorporated into the optimized liquid PCB-loaded SNEDDS (L-PLSNE-8), solidified using Neusilin-US2 (S-PLSNE-8), and characterized for morphology by transmission electron microscopy (TEM) (L-PLSNE-8), crystallinity by X-ray diffraction, in vitro drug release, Caco-2 cell permeability, cytotoxicity, apoptotic potential, and pharmacokinetic parameters. The optimized L-PSNE-8, composed of Maisine (15%), Cremophor RH-40 (40%), and labrasol, demonstrated reduced self-emulsification time (90 ± 1.08 sec) and a high transmittance (99.26 ± 1.71%). L-PLSNE-8 showed nanoscale spherical globules in TEM analysis. The FTIR spectra of S-PLSNE-8 revealed no incompatibility between the drug and excipients. DSC and XRD analysis of the S-PLSNE-8 demonstrated the amorphization and molecular dispersion of PCB and LTZ. S-PLSNE-8 exhibited a complete drug release (99.76 ± 0.75%) compared to plain drug dispersions in 0.1N HCl after 20 min of release study. The release profiles in phosphate buffer at pH 6.8 were observed to be slightly greater than those in 0.1N HCl. S-PLSNE-8 significantly (P<0.001) decreased the growth of MCF-7 breast cancer cells and increased their apoptosis (P < 0.001). Compared to plain drugs, S-PLSNE-8 showed almost a 4- and 2-fold increase in Caco-2 cell permeability of PCB and LTZ, respectively. Oral pharmacokinetic study of S-PLSNE-8 revealed a 7.5- and 4-fold increase in bioavailability for LTZ and PCB, respectively, compared to plain drugs. These findings suggest that S-PLSNE-8 is a promising oral drug delivery system for poorly soluble and permeable drugs in breast cancer treatment.

Formulation of Letrozole-loaded Ethyl Cellulose and Eudragit S100 Nanoparticles by Nanoprecipitation Technique and Determination of Cytotoxic Activity by MTT Assay

Introduction: The major goal of this work is to develop letrozole nanoparticles using the polymer precipitation technique. Formulations were prepared by using Ethyl cellulose and Eudragit S100 as polymers. Methods: By varying drug-polymer ratios, a total of ten formulations were prepared. By altering the drug concentration to polymer, five formulations were prepared with Ethyl cellulose and five with Eudragit S100. All ten formulations were evaluated for different characterization and evaluation parameters such as Entrapment efficiency, Loading capacity and in vitro drug release studies, particle size, stability (zeta potential), surface morphology, and drug-polymer interaction study. Result: In comparison, the NEC 2:1 formulation showed the smallest particle size,high stability, good entrapment efficiency, and sustained drug release. This formulation was further studied to determine the anticancer activity in vitro in the MCF-7 Breast cancer cell line by MTT assay. The results indicated that the prepared formulation exhibited anticancer activity with an IC50 value of 91.26 micromolar. Conclusion: Comparatively, Ethyl cellulose was proven to be a better polymer than Eudragit S100, and the nanoprecipitation technique was considered the most suitable technique for preparing letrozole nanoparticles.

GC/MS analysis and green-synthesis of silver nanoparticles using Senna auriculata flower extract: Antibacterial, antioxidant effects and anticancer effects.

In the present state of nano drug research, the production of herbal nutritionally aided nanoparticles has a broad variety of applications of new non side effect medical medications, as long as they are founded with environmentally acceptable methods. Silver nanoparticles in the form of phytochemicals from traditional herbal remedies, specifically the flower of senna auriculata, have been produced. The green synthesized silver nanoparticles were subsequently characterized by UV-Visible spectroscopy, Transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction and Thermo gravity analysis. In the current study on the green synthesis approach, one of the best candidates, Ag nanoparticles act as a potential agent to investigate the antibacterial activity by a well diffusion method. The green synthesized AgNPs had the highest significant antibacterial activity against Gram-negative bacteria E. coli at 100μg/mL, as well as, the AgNPs exhibited great inhibitory effects on DPPH radicals and their antioxidant properties were favorably comparable to the antioxidant outcomes of ascorbic acid. Furthermore, at 100μg/mL concentration, the S. auriculata silver nanoparticles showed substantial cytotoxic effects against human breast cancer MCF-7cell lines when compared to their effect on the normal cell line tested. The GC-MS analysis of the S. auriculata extract showed that 55 bioactive phytochemical compounds, which may be of use to the synthesis of AgNPs. Hence, the green synthesized silver nanoparticles from flower extract S. auriculata can be employed for biomedical applications.

Synthesis and biological evaluation of oleanolic acid derivatives as potential c-kit inhibitors

The 3-O-(4′-imidazole)-12-en-olean-28-amide derivatives 7-1 to 7-11 through modification the C-3 and C-28 of the natural product oleanolic acid were prepared, and their structures were confirmed by MS,1H NMR and 13C NMR. The antitumor activities of these compounds against breast cancer MCF-7 and gastric cancer SGC7901 cells in vitro were determined by MTT assay. Cell tests showed that the antitumor activities of compound 7-10 exhibited significant antitumor activity which was equivalent to the positive control drug nilotinib, and the affinity was verified by molecular dynamics experiment in vitro. Molecular docking showed that compound 7-10 have high binding ability with c-kit. Therefore, compound 7-10 has the potential to become a new c-kit inhibitor, which deserves further research.

Azurin a potent anticancer and antimicrobial agent isolated from a novel Pseudomonas aeruginosa strain

Azurin, a bacterial blue-copper protein, has garnered significant attention as a potential anticancer drug in recent years. Among twenty Pseudomonas aeruginosa isolates, we identified one isolate that demonstrated potent and remarkable azurin synthesis using the VITEK 2 system and 16S rRNA sequencing. The presence of the azurin gene was confirmed in the genomic DNA using specific oligonucleotide primers, and azurin expression was also detected in the synthesized cDNA, which revealed that the azurin expression is active. Furthermore, crude azurin protein was extracted, precipitated using 70% ammonium sulfate, dialyzed, and subjected to purification using carboxymethyl-Sephadex in affinity chromatography as a cheap method for purification. The partially purified azurin protein was characterized using polyacrylamide gel electrophoresis, energy-dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy, and nuclear magnetic resonance spectroscopy. Notably, qualitative elemental analysis by EDX showed the presence of copper and sulfur, corresponding to the copper-core and disulfide-bridge, respectively, in the purified azurin fraction. Moreover, FTIR spectroscopy revealed characteristic amide I and II absorption peaks (1500–1700 cm− 1), revealing the possible secondary structure of azurin. The results of NMR revealed the presence of characteristic amino acids such as methionine and cysteine, which confirmed the EDX results for sulfur-containing amino acids. Purified azurin exhibited antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Klebsiella pneumoniae. Additionally, its anticancer properties were determined using the MTT assay and cell cycle analysis, revealing a preference for inhibiting the MCF7 breast cancer cell line where breast cancer is most common in Egypt. Overall, the research findings suggest that the local isolate, P. aeruginosa strain 105, could be a potential source of azurin protein for incorporation into cancer treatment strategies.

RNA binding protein ILF3 increases CEP55 mRNA stability to enhance malignant potential of breast cancer cells and suppress ferroptosis

BackgroundFerroptosis has emerged as a promising therapeutic target in cancer treatment. CEP55, a key regulator of cell mitosis, plays a significant role in the tumorigenesis of many malignancies. In this study, we elucidated the function of CEP55 in the ferroptosis of breast cancer (BC).MethodsThe protein levels of CEP55 and ILF3 were detected by immunoblotting or immunohistochemistry, and their mRNA levels were assessed by quantitative PCR. Cell invasion and migration were evaluated by transwell assay. Cell apoptosis and colony formation were tested by flow cytometry and colony formation assays, respectively. RNA immunoprecipitation (RIP) experiment and CEP55 mRNA stability assay were used to validate the relationship between ILF3 and CEP55 mRNA. Subcutaneous xenograft studies were performed to analyze the role of ILF3 depletion in tumor growth.ResultsCEP55 and ILF3 were upregulated in most of human BC samples and MDA-MB-231 and MCF-7 BC cells. The depletion of CEP55 or ILF3 impaired the growth, invasion, and migration of MDA-MB-231 and MCF-7 cells, while promoted their ferroptosis and apoptosis. Mechanistically, ILF3 stabilized CEP55 mRNA to regulate CEP55 expression in BC cells. CEP55 restoration partially rescued the malignant potential defects of ILF3-depleted BC cells and attenuates their ferroptosis. Moreover, ILF3 depletion enhanced the anti-tumor growth activity of the ferroptosis inducer erastin in MDA-MB-231 subcutaneous xenograft tumors.ConclusionOur observations indicate that the depletion of ILF3 impairs the malignant potential of BC cells and promotes their ferroptosis by downregulating CEP55 expression. Silencing ILF3 or CEP55 could represent a potential therapeutic strategy for BC treatment.Graphical abstract

Cytotoxic Effects Of Lecaniodiscus Cupanioides (Planch.) Extract and Triterpenoids-derived Gold Nanoparticles On MCF-7 Breast Cancer Cell Lines.

The prevalent disease known as breast cancer has a significant impact on both men's and women's health and quality of life. The aim of this study was to explore the potential roles of Lecaniodiscus cupanioides (planch.) extract and triterpenoid-derived gold nanoparticles (AuNPs) in cancer therapy, specifically targeting MCF-7 breast cancer cell lines. Gold nanoparticles were synthesized utilizing triterpenoid (ZJ-AuNPs) and leaf extract from Lecaniodiscus cupanioides (LC-AuNPs). Fourier transform infrared spectroscopy (FTIR), Dynamic light scattering (DLS), High-resolution transmission electron microscopy (HRTEM), and UV-vis spectroscopy were employed to characterize the nanoparticles. Additionally, the MTT assay was used to assess the impact of AuNPs on cancer cell viability using MCF-7 breast cancer cell lines. Analysis of ZJ-AuNPs and LC-AuNPs revealed DLS zeta potentials of -31.8 and -35.8 mV, respectively, and a corresponding UV-vis absorption maxima at 540 and 550 nm. Also, the ZJ-AuNPs and LC-AuNPs had respective zeta-sizes that ranged from 25.84 to 35.98 nm and polydispersive index values between 0.2360 and 0.773.Furthermore, the presence of the chemical groups -OH and -NH was shown to be necessary for the green method of capping and reducing the gold nanoparticles. Nevertheless, a significant decrease in cell viability percentages was noted in the MTT experiment, accompanied by an increase in the quantity or concentration of the nanoparticles for both ZJ-AuNPs and LC-AuNPs. Given the data obtained in this study, the biosynthesized ZJ-AuNPs and LC-AuNPs were shown to possess potent cytotoxic effects on breast cancer cells. Hence, they may be valuable tools in the development of new cancer chemotherapy drugs.

Synergistic Anticancer Activity of Quercetin Combined with Luteolin in MCF-7 Breast Cancer Cells via Induction of Apoptosis

Cancer is a major public health problem with its increasing incidence and mortality. The striking role of phytochemicals in the prevention and treatment of cancer is undeniable in studies. In this study, the effects of the combination of quercetin (QUR) and luteolin (LTN) on the MCF-7 human breast cancer cell line were investigated in vitro. WST-1 cell cytotoxicity assay was used to determine cytotoxic activity. The effects on colony survival and cell migration were determined by clonogenic assay and wound scratch assay, respectively. For the determination of apoptosis, AO/EB dual staining, and Caspase-3 ELISA analysis, and genomic analyses revealing p53, Bcl-2, and Bax expression levels were performed. As a result of the analyses, it was seen that especially QUR plus LTN treatment exhibited a great cytotoxic activity in cells. It was determined that the combination treatment suppressed colony survival and significantly inhibited cell migration. Quantitative analysis results show that QUR+LTN treatment triggers cellular apoptosis by upregulating Caspase-3, p53, and Bax, and downregulating Bcl-2. Supporting these findings with further in vitro and in vivo analyses may contribute significantly to revealing the promising efficacy of combined phytochemical treatment approaches on cancer.

Investigation of Antioxidant, Antimicrobial and Cytotoxic Activities of Different Extracts of Muscari armeniacum

The aim of this study is to comparatively evaluate the antioxidant and antimicrobial activities of different extracts obtained by the maceration method of the aerial and bulbs of the Muscari armeniacum. Additionally, the study aims to determine the effect of ethanol extracts on the proliferation of human fibroblasts and MCF-7 breast cancer cell lines. The antioxidant activities of petroleum ether, chloroform and ethanol extracts from the aerial parts and bulbs of the Muscari armeniacum were examined by DPPH, CUPRAC and FRAP methods. The amount of total phenolic compounds contained in the extracts was determined using the FCR method. Antimicrobial activity was determined by the agar well diffusion method. The ability ethanol extracts of plant to cytotoxic activity was determined using the MTT assay. It was determined that the chloroform extract of bulbs had higher DPPH (IC50:0.056 mg/mL), FRAP (2.738 mM FeSO4/mg extract) and CUPRAC (3.640 mM trolox equivalent/mg extract) activity potential than other extracts. In addition, it was determined that the aerial parts chloroform extract showed the highest DPPH (IC50: 0.889 mg/mL), CUPRAC (1.166 mM trolox equivalent/mg extract) and FRAP (0.823 mM FeSO4/mg extract activities) antioxidant activity. It was determined that the chloroform extract obtained from bulbs contained higher amounts of phenolic contents than the aerial parts and accordingly showed the highest antioxidant activity. Aerial parts petroleum ether extract was found to have antimicrobial activity against S. aureus ATCC 25923 and S. epidermidis ATCC 11228, and the ethanol extract of bulbs was found to have antimicrobial activity only against S. epidermidis ATCC 11228. The study showed no cytotoxic potential of aerial parts and bulbs ethanol extracts at a dose of 500 µg/mL on human fibroblasts and MCF-7 breast cancer cell lines. The fact that different parts of the plant do not show cytotoxic activity on human normal cell lines suggests that this species can be used as an antioxidant and antimicrobial agent.

Eksplorasi Endofit Sambung Nyawa: Potensi Mikroba dalam Penemuan Obat dan Bioaktivitasnya

Gynura procumbens, also known as “Sambung Nyawa,” is a medicinal plant known for its various therapeutic properties. This study aims to explore the potential of endophytic microbes living inside Gynura procumbens plants as a source of bioactive compounds with pharmaceutical applications. Endophytic microbes are microorganisms that live symbiotically in plant tissues without causing damage, and are known to produce secondary metabolites similar to their host plants. In this study, endophytic microbes in the form of bacteria and fungi were isolated from various plant parts, including leaves, stems, and roots. A total of 12 isolates were obtained, consisting of 7 bacteria and 5 fungi, which were identified using molecular techniques. The isolates were tested for antimicrobial, antioxidant and cytotoxic activities. The antimicrobial assay showed significant inhibitory effects against Staphylococcus aureus and Candida albicans, where isolates from the genus Streptomyces and Penicillium had the highest activity. Antioxidant activity was measured using the DPPH method, and two bacterial isolates showed strong free radical scavenging ability. Cytotoxic assays on MCF-7 breast cancer cells revealed that the fungal isolates, mainly from the genus Penicillium and Aspergillus, had strong anticancer activity. The results of this study indicate that endophytic microbes from Gynura procumbens contain bioactive compounds that have potential as antimicrobial, antioxidant, and anticancer agents. This study confirms the importance of exploring endophytic microbes from medicinal plants in the discovery of new drugs and the development of therapeutic agents. Further research is needed to isolate and characterize the specific compounds responsible for these bioactivities as well as evaluate their potential in clinical applications.

Dual ligand functionalized pH-sensitive liposomes for metastatic breast cancer treatment: in vitro and in vivo assessment.

This research demonstrates the design and development of a novel dual-targeting, pH-sensitive liposomal (pSL) formulation of 5-Fluorouracil (5-FU), i.e., (5-FU-iRGD-FA-pSL) to manage breast cancer (BC). The motivation to explore this formulation is to overcome the challenges of systemic toxicity and non-specific targeting of 5-FU, a conventional chemotherapeutic agent. The proposed formulation also combines folic acid (FA) and iRGD peptides as targeting ligands to enhance tumor cell specificity and penetration, while the pH-sensitive liposomes ensure the controlled drug release in the acidic tumor microenvironment. The physicochemical characterization revealed that 5-FU-iRGD-FA-pSL possesses optimal size, low polydispersity index, and favorable zeta potential, enhancing its stability and targeting capabilities. In vitro studies demonstrated significantly enhanced cellular uptake, cytotoxicity, and inhibition of cell migration in MCF-7 BC cells compared to free 5-FU and non-targeted liposomal formulations. DAPI staining revealed significant apoptotic features, including chromatin condensation (CC) and nuclear fragmentation (NF), with 5-FU-iRGD-FA-pSL inducing more pronounced apoptosis compared to 5-FU-pSL. Furthermore, in vivo analysis in a BC rat model showed superior anti-tumor efficacy, reduced systemic toxicity, and improved safety profile of the 5-FU-iRGD-FA-pSL formulation. This dual-targeting pSL system presents a promising approach for enhancing the therapeutic index of 5-FU, offering a potential strategy for more effective BC treatment.

Thyroid Hormone Activation Regulates the Crosstalk between Breast Cancer and Mesenchymal Stem Cells.

Thyroid Hormones (THs) critically impact human cancer. Although endowed with both tumor-promoting and inhibiting effects in different cancer types, excess of THs has been linked to enhanced tumor growth and progression. Breast cancer depends on the interaction between bulk tumor cells and the surrounding microenvironment in which mesenchymal stem cells (MSCs) exert powerful pro-tumorigenic activities. Primary human MSCs from healthy female donors were co-cultured with DIO2 knock out (D2KO) and wild type (WT) MCF7 breast cancer cells to assess cell growth, migration, invasion and the expression of known epithelial-mesenchymal transition (EMT)- and inflammation-related markers. Furthermore, a surgery-free intraductal delivery model, i.e., the Mouse-INtraDuctal (MIND) injection method, was used as a tool for in vivo characterization of breast tumor formation and progression. In this study, we uncovered a novel role of THs in regulating the tumor-stroma crosstalk. MCF7 cells enhanced the intracellular activation of THs through the TH-activating enzyme, D2, fostering their EMT properties and the dialogue with MSCs. D2 inactivation reduced the invasiveness of MCF7 cells and their responsiveness to the pro-tumorigenic induction via MSCs, both in vivo and in vitro. Thus, we argue that intracellular activation of THs via D2 is a critical requirement for invasive and metastatic conversion of breast cancer cells, advising the blocking of D2 as a potential therapeutic tool for cancer therapy.

Biosynthesis, characterization, and multifaceted applications of Elytraria acaulis synthesized silver and gold nanoparticles: Anticancer, antibacterial, larvicidal, and photocatalytic activities.

Green synthesis of metal nanoparticles using plant extracts has emerged as an eco-friendly alternative to conventional methods, offering potential applications in biomedicine and environmental remediation. This study demonstrates the successful biosynthesis of silver nanoparticles (SNPs) and gold nanoparticles (GNPs) using Euphorbia acaulis leaf extract as a reducing and capping agent. The nanoparticles were thoroughly characterized using UV-Vis spectroscopy, HR-SEM, EDX, TEM, AFM, XRD, and FTIR analyses, confirming their successful synthesis and revealing their predominantly spherical morphology with sizes ranging from 1 to 100nm. SNPs and GNPs exhibited significant anticancer activity against MCF-7 breast cancer cells, with IC50 values of 59.87μg/mL and 91.074μg/mL, respectively. The nanoparticles induce apoptosis and DNA damage in cancer cells, as evidenced by propidium iodide staining, DAPI staining, and comet assay. In antibacterial studies, SNPs demonstrated superior activity against both E. coli (17.00mm zone of inhibition) and S. aureus (10.77mm zone of inhibition) compared to GNPs. The nanoparticles also showed promising larvicidal activity against Aedes aegypti, with SNPs exhibiting higher potency (LC50: 20.81mg/L) than GNPs (LC50: 51.10mg/L). Histopathological analysis revealed significant tissue damage in SNP-treated larvae, particularly in the midgut, hindgut, muscles, and nerve ganglia. Additionally, both nanoparticles demonstrated photocatalytic activity in degrading methylene blue dye, with SNPs showing superior performance. These findings suggest that biofunctionalized SNPs and GNPs synthesized using E. acaulis possess multiple biological applications, making them promising candidates for various biomedical and environmental applications.

(E)-1-(3-(3-Hydroxy-4-Methoxyphenyl)-1-(3,4,5-Trimethoxyphenyl)allyl)-1H-1,2,4-Triazole and Related Compounds: Their Synthesis and Biological Evaluation as Novel Antimitotic Agents Targeting Breast Cancer.

Background/Objectives: The synthesis of (E)-1-(1,3-diphenylallyl)-1H-1,2,4-triazoles and related compounds as anti-mitotic agents with activity in breast cancer was investigated. These compounds were designed as hybrids of the microtubule-targeting chalcones, indanones, and the aromatase inhibitor letrozole. Methods: A panel of 29 compounds was synthesized and examined by a preliminary screening in estrogen receptor (ER) and progesterone receptor (PR)-positive MCF-7 breast cancer cells together with cell cycle analysis and tubulin polymerization inhibition. Results: (E)-5-(3-(1H-1,2,4-triazol-1-yl)-3-(3,4,5-trimethoxyphenyl)prop-1-en-1-yl)-2-methoxyphenol 22b was identified as a potent antiproliferative compound with an IC50 value of 0.39 mM in MCF-7 breast cancer cells, 0.77 mM in triple-negative MDA-MB-231 breast cancer cells, and 0.37 mM in leukemia HL-60 cells. In addition, compound 22b demonstrated potent activity in the sub-micromolar range against the NCI 60 cancer cell line panel including prostate, melanoma, colon, leukemia, and non-small cell lung cancers. G2/M phase cell cycle arrest and the induction of apoptosis in MCF-7 cells together with inhibition of tubulin polymerization were demonstrated. Immunofluorescence studies confirmed that compound 22b targeted tubulin in MCF-7 cells, while computational docking studies predicted binding conformations for 22b in the colchicine binding site of tubulin. Compound 22b also selectively inhibited aromatase. Conclusions: Based on the results obtained, these novel compounds are suitable candidates for further investigation as antiproliferative microtubule-targeting agents for breast cancer.

Two-Step Acoustic Cell Separation Based on Cell Size and Acoustic Impedance─toward Isolation of Viable Circulating Tumor Cells.

Isolation and characterization of circulating tumor cells (CTCs) present a noninvasive alternative to monitor disease progression in individual patients. However, the heterogeneous lineage specificity of CTCs makes it difficult to isolate and identify possible CTCs by a liquid biopsy. Better label-free methods for the isolation of viable CTCs are needed. Our solution is a combined approach that is inherently epitope independent. Cells are separated by size-sensitive acoustophoresis using an ultrasonic standing wave field, followed by size-insensitive, acoustic barrier-medium focusing, which enables the enrichment of viable cancer cells in blood. With standard acoustophoresis in homogeneous medium, lymphocytes and monocytes were efficiently removed, while removal of granulocytes from the target MCF7 breast cancer cells was not possible due to overlapping acoustic migration velocities for viable cells. Remaining granulocytes were removed by a second separation step with an acoustic impedance barrier-medium selectively blocking the transport of MCF7 cells to generate a clean cancer cell fraction. For two series of 500 mL samples containing 5 × 105 white blood cells, spiked with 2 × 104 or 1 × 103 MCF7 cells, the recovery of MCF7 cells was 77.3% with a 99.9% depletion of white blood cells in the final cancer cell fraction. The most abundant contaminating cell type was granulocytes (85.9% of remaining cells). Nearly all lymphocytes (99.996%) and monocytes (99.995%) were depleted. A two-step acoustic cell separation based on cell size and acoustic impedance is well suited to generate a purified cancer cell fraction as a preparatory step for downstream single-cell analysis.