Breast Cancer Cell Line MCF-7 Research Articles

Synthesis of novel coumarin-triazole hybrids and first evaluation of the 4-phenyl substituted hybrid loaded PLGA nanoparticles delivery system to the anticancer activity.

Despite the discovery of many chemotherapeutic drugs that prevent uncontrolled cell division processes in the last century, many studies are still being carried out to develop drugs with higher anticancer efficacy and lower level of side effects. Herein, we designed, synthesized, and characterized six novel coumarin-triazole hybrids, and evaluated for anticancer activity of the one with the highest potential against the breast cancer cell line, MCF-7 and human cervical cancer cell line, human cervical adenocarcinoma (HeLa). Compound21which was the coumarin derivative including phenyl substituent with the lowest IC50 value displayed the highest cytotoxicity against the studied cancer cell line. Furthermore, the potential use of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) prepared by the emulsifying solvent evaporation method as a platform for a drug delivery system was studied on a selected coumarin derivative21. This coumarin derivative-loaded PLGA NPs were produced with an average size of 225.90 ± 2.96 nm, -16.90 ± 0.85 mV zeta potential, and 4.12 ± 0.90% drug loading capacity. The obtained21-loaded PLGA nanoparticles were analyzed spectroscopically and microscopically with FT-IR, UV-vis, and scanning electron microscopy as well as thermogravimetric analysis, Raman, and x-ray diffraction. Thein vitrorelease of21from the nanoparticles exhibited a controlled release profile just over one month following a burst release in the initial six hours and in addition to this a total release ratio of %50 and %85 were obtained at pH 7.4 and 5.5, respectively.21-loaded PLGA nanoparticles displayed remarkably effective anticancer activity than21. The IC50 values were determined as IC50(21-loaded PLGA nanoparticles): 0.42 ± 0.01 mg ml-1and IC50(free21molecule): 5.74 ± 3.82 mg ml-1against MCF-7 cells, and as IC50(21-loaded PLGA nanoparticles): 0.77 ± 0.12 mg ml-1and IC50(free21molecule): 1.32 ± 0.31 mg ml-1against HeLa cells after the incubation period of 24 h. Our findings indicated that triazole-substituted coumarins may be used as an anticancer agent by integrating them into a polymeric drug delivery system providing improved drug loading and effective controlled drug release.

Molecular interactions between metformin and D-limonene inhibit proliferation and promote apoptosis in breast and liver cancer cells

BackgroundCancer is a fatal disease that severely affects humans. Designing new anticancer strategies and understanding the mechanism of action of anticancer agents is imperative.Hypothesis/PurposeIn this study, we evaluated the utility of metformin and D-limonene, alone or in combination, as potential anticancer therapeutics using the human liver and breast cancer cell lines HepG2 and MCF-7.Study designAn integrated systems pharmacology approach is presented for illustrating the molecular interactions between metformin and D-limonene.MethodsWe applied a systems-based analysis to introduce a drug–target–pathway network that clarifies different mechanisms of treatment. The combination treatment of metformin and D-limonene induced apoptosis in both cell lines compared with single drug treatments, as indicated by flow cytometric and gene expression analysis.ResultsThe mRNA expression of Bax and P53 genes were significantly upregulated while Bcl-2, iNOS, and Cox-2 were significantly downregulated in all treatment groups compared with normal cells. The percentages of late apoptotic HepG2 and MCF-7 cells were higher in all treatment groups, particularly in the combination treatment group. Calculations for the combination index (CI) revealed a synergistic effect between both drugs for HepG2 cells (CI = 0.14) and MCF-7 cells (CI = 0.22).ConclusionOur data show that metformin, D-limonene, and their combinations exerted significant antitumor effects on the cancer cell lines by inducing apoptosis and modulating the expression of apoptotic genes.

Discovery of Alkyl Triphenylphosphonium Pinostrobin Derivatives as Potent Anti-Breast Cancer Agents.

Pinostrobin demonstrated anticancer properties, but its hydrophobic feature led to a reduction in bioavailability. The mitochondria-targeted approach successfully synthesized eight new alkyl triphenylphosphonium pinostrobin derivatives (1-8) with good yield in this study. Seven compounds (1-3, 5-8) showed greater cytotoxic potency against the human MCF-7 breast cancer cell line than pinostrobin. Molecular docking studies were performed with two important targets in hormone-dependent anticancer strategies, estrogen receptor α (ERα) ligand binding domains, 3ERT (antagonist recognition and antiproliferative function), and 1GWR (agonist recognition and pro-proliferative function). In addition, the MD simulation study of the two most potent compounds (2 and 3) complexed with both ERα forms suggested that compounds 2 and 3 could serve as favourable antagonists. Furthermore, the in silico ADMET prediction indicated that compounds 2 and 3 could be potential drug candidates.

Abstract PO2-24-04: Exploring the role and therapeutic potential of Ubiquitin Specific Peptidase 11 (USP11) in estrogen receptor positive breast cancer

Abstract Dysregulated estrogen receptor (ER) function is a key feature of 70% of breast cancers. In this setting ER primarily functions as a growth-controlling transcription factor driving pro-tumorigenic properties, thus there is a need to identify novel modulators of ER transcriptional activity as alternative therapeutic options. Previously, we showed a significant association between high ubiquitin specific protease 11 (USP11) expression and poor survival in ER+ breast cancer patients, but not in ER- patients, indicating a role for USP11 in ER+ subtypes. However, the precise role of USP11 in controlling ER function remains undescribed. To interrogate USP11 function in ER+ breast cancer we generated a CRISPR USP11 knockout MCF7 breast cancer cell line. Our results showed for the first time that USP11 knockout significantly reduces proliferation, induces G2 cell cycle arrest and apoptosis, abrogates ERα transcriptional activity, significantly impairs cell migration and invasion, whilst also impairing MCF7 cancer stem-cell like properties and malignant transformation in vitro. In addition, we also observed significant dysregulation of epithelial-mesenchymal transition-related markers including E-cadherin, N-cadherin, Snail and Slug. Using RNA-seq of MCF7 cells +/- estradiol, +/- stable USP11 knockdown we identified dysregulated pathways in protein binding, cell adhesion molecule binding and cell cycle regulation following USP11 modulation. Of note, gene expression analysis indicated NCOA3 as the most differentially expressed coding gene. Further validation confirmed a significant reduction in NCOA3- encoded Steroid receptor coactivator- 3 (SRC-3) protein expression following USP11 modulation with immunocytochemical analysis also indicating co-localisation within the nucleus. Frequently upregulated in breast cancer and associated with poor outcome, SRC-3 promotes ER transcriptional activity and co-activates a wide range of additional pro-tumorigenic transcription factors. Thus, SRC-3 modulation offers an attractive therapeutic target in breast cancer. This finding may present a novel role for USP11 in controlling SRC-3 and therefore associated ER transcriptional activity. We then aimed to explore the therapeutic potential of USP11. Although rare in primary breast cancer, activating mutations in the ER ligand-binding domain have recently been linked to recurrent, anti-endocrine resistant disease and metastasis. As such cancers remain dependent on ER-signalling for proliferation, but are resistant to ER targeted therapies, we identified USP11 as a potential novel therapeutic target. Using CRISPR knock-in ER mutant MCF7 cell lines expressing the four most common ER activating mutations, we demonstrated that USP11 knockdown continues to significantly reduce proliferation and abrogates mutant ERα transcriptional activity. We then explored amphipathic cell penetrating peptide RALA encapsulation as a delivery method for siRNA targeting USP11. Optimisation of nanoparticle delivery in the Y537S ER-mutant MCF7 breast cancer cell line achieved significant knockdown of USP11 and ER- related target genes including TFF1, PgR, GREB1 and PKIB in 2D with minimal associated cellular toxicity. To overcome the siRNA-related issues of rapid clearance upon systemic delivery, we then explored the use of a freeze-dried collagen-based scaffold model as an in vitro 3D RALA-encapsulated siRNA delivery system. Here we observed successful delivery of nanoparticle to MCF7 breast cancer cells, with a significant reduction in USP11 mRNA expression. Bio-compatible scaffold- facilitated delivery may therefore offer a more feasible translation of this siRNA-based therapeutic. Overall, this study highlights a novel role for USP11 in various oncogenic pathways. USP11 may therefore offer a novel therapeutic target to be exploited for the management of ER-positive breast cancer, including ER mutant breast cancer. Citation Format: Rachel Moore, Anna Blümel, Elspeth Ward, Elizabeth Sainsbury, Emer Conroy, Fergal O’Brien, Caroline Curtin, Simak Ali, Helen McCarthy, William Gallagher, Darran O'Connor. Exploring the role and therapeutic potential of Ubiquitin Specific Peptidase 11 (USP11) in estrogen receptor positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-24-04.

Abstract GS03-10: Allosteric PI3K-alpha inhibition overcomes on-target resistance to orthosteric inhibitors mediated by secondary PIK3CA mutations

Abstract Background: PIK3CA mutations occur in ~40% of HR-positive breast cancers, where alpelisib, an orthosteric PI3Kα inhibitor, is FDA-approved in combination with fulvestrant. Although prior studies have identified potential resistance mechanisms, such as PTEN loss, clinical acquired resistance to orthosteric PI3Kα inhibitors and the role of next-generation allosteric PI3Kα inhibitors remain poorly understood. Methods: To identify on-target and off-target alterations potentially mediating resistance to PI3Kα inhibitors, we used a targeted next-generation sequencing assay (Guardant360; Guardant Health) to analyze ctDNA in serially collected plasma samples from 32 patients with PIK3CA-mutated advanced HR-positive, HER2-negative breast cancer treated with alpelisib and inavolisib. In addition, we performed whole exome sequencing (WES) of 100 tissue samples collected from 8 autopsy series from patients with metastatic, PIK3CA-mutant HR-positive, HER2-negative breast cancer previously treated with PI3Kα inhibitors. Acquired alterations were prioritized through a combination of structural modeling and free-energy perturbation simulation and validated in genomically engineered PIK3CA mutant breast cancer cell lines T47D (PIK3CA H1047R-mutant) or MCF7 (PIK3CA E545K-mutant). Results: We observed that 50% of patients acquire genomic alterations within the PI3K-pathway, including PTEN loss and activating AKT1 mutations. Notably, while secondary PIK3CA mutations were previously reported to increase sensitivity to PI3Ka-inhibitors, we identified emergent secondary resistance mutations in PIK3CA that alter the inhibitor binding pocket including PIK3CA Q859K and PIK3CA W780R. Some mutations had differential effects on PI3Ka-selective vs. pan-PI3K inhibitors, but resistance induced by all mutations could be overcome by the novel allosteric pan-mutant-selective PI3Ka-inhibitor RLY-2608. Conclusion: In one of the largest patient cohorts analyzed to date, this study defines the clinical landscape of acquired resistance to PI3Ka inhibitors. Genomic alterations within the PI3K pathway represent a major mode of resistance and identify a novel class of secondary PIK3CA resistance mutations that can be overcome by an allosteric PI3Ka inhibitor. Together, these findings provide insights to guide strategies to overcome resistance in PIK3CA-mutated cancers. Citation Format: Andreas Varkaris, Ferran Fece de la Cruz, Elizabeth Martin, Bryanna Nordern, Nicholas Chevalier, Ignaty Leshchiner, Anastasia Stavridi, Janice Kim, Alkistis Papatheodoridi, Hakan Gunaydin, Brian Danysh, Laxmi Parida, Ioannis Sanidas, Yongli Ji, Kayao Lau, Gerburg Wulf, Aditya Bardia, Laura Spring, Steven Isakoff, Jochen Lennerz, Levi Pierce, Ermira Pazolli, Gad Getz, Ryan Corcoran, Dejan Juric. Allosteric PI3K-alpha inhibition overcomes on-target resistance to orthosteric inhibitors mediated by secondary PIK3CA mutations [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS03-10.

Abstract PO1-13-08: Comparative analysis of stearoyl-CoA desaturase 1 expression and activity index in model cell lines of breast cancer subclasses

Abstract Introduction Due to the unique conditions of the tumor microenvironment, such as hypoxia, poor angiogenesis, and mitochondrial dysfunction, cancer cells face challenges in obtaining nutrients and energy supply. However, monounsaturated fatty acids have been identified as preferred substrates for energy generation and maintenance of cellular structures in cancer cells. These fatty acids can be obtained through de novo fatty acid synthesis. Stearoyl-CoA desaturase 1 (SCD1) is the primary enzyme involved in the biosynthesis of monounsaturated fatty acids from saturated fatty acids and is known to be upregulated in various malignancies, including breast cancer. This study aimed to assess the expression and activity index of SCD1 in well-characterized MCF-7, SK-BR3, and MDA-MB231 breast cancer cell lines, representing luminal A/B, HER2-enriched, and triple-negative subtypes, respectively. Methods The breast cancer cell lines were cultured in RPMI-1640 medium with 10% fetal bovine serum at 37°C, 5% CO2, and 95% humidity for 72 hours. After harvesting the cells, SCD1 expression was analyzed using real-time quantitative PCR, and the activity index was determined by measuring the ratio of monounsaturated fatty acids to saturated fatty acids using capillary gas-liquid chromatography. Results MCF-7 cell line showed a significantly higher SCD1 expression compared to MDA-MB231 (250-fold, p< 0.0001) and SK-BR3 (83-fold, p< 0.0001) cell lines. The activity index of SCD1 was significantly higher in both MCF-7 and MDA-MB231 cell lines with fold changes of 2.6 and 2.5, respectively, compared to SK-BR3 cell line (p=0.004 for both). Conclusion Cell model assays demonstrated that the luminal A/B and triple-negative subtypes showed a higher capacity to convert saturated fatty acids to monounsaturated fatty acids through SCD1 enzyme activity, indicating a different lipid metabolism profile in the HER2-enriched subtype. These new findings reveal differences in SCD1 expression and activity among breast cancer subclasses. They highlight vulnerabilities in metabolism and identify potential therapeutic targets with clinical implications for managing breast cancer. Citation Format: Hamid-Reza Feizi, Amir Mehdizadeh, Zohreh Sanaat, Khadijeh Abbasi, Frank Gieseler, Masoud Darabi. Comparative analysis of stearoyl-CoA desaturase 1 expression and activity index in model cell lines of breast cancer subclasses [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-13-08.

Abstract PO1-18-05: Combination treatment with CDK2 inhibitor (BLU-222) and either palbociclib or ribociclib is synergistic in pre-clinical models of CDK4/6 inhibitor-resistant breast cancer

Abstract Background: Cyclin-dependent-kinase-4/6 inhibitors (CDK4/6 inhibitors) plus endocrine therapy (ET) is the standard of care first-line treatment for patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC). However, since most patients progress following long-term treatment, resistance to CDK4/6 inhibitors plus ET remains a clinical problem with limited therapeutic options. Here we show that a potent and selective CDK2 inhibitor, BLU-222, while effective as a single agent, exhibited enhanced, synergistic activity when combined with palbociclib or ribociclib in both in vitro and in vivo (patient-derived xenografts-PDX) models of HR+/HER2- breast cancer resistant to CDK4/6 inhibitors. Methods: MCF7 and T47D palbociclib-resistant (PR) breast cancer cell lines were generated by culturing cells in media supplemented with increasing concentrations of palbociclib, starting at 1.2 µM and reaching a final concentration of 4.8 µM in a stepwise manner over a 6-month period. The single agent activity of BLU-222 and the combination effect of BLU-222 plus palbociclib in vitro were evaluated using the highest single agent model by SynergyFinder. The efficacy of BLU-222 as a single agent or in combination with palbociclib or ribociclib was also assessed in two PDX models (PR 1 and 2) from patients with acquired resistance (i.e. progressed following >6 months of treatment) to palbociclib plus letrozole treatment, and another two PDX models (PR 3 and 4) from patients who were intrinsically resistant (i.e. progressed following < 3 months of treatment) to palbociclib plus fulvestrant or letrozole, respectively. Results: In palbociclib-resistant MCF7 and T47D cells, protein levels of cyclin E and CDK2 were significantly upregulated, but Rb and p21 levels were downregulated compared to the parental cells. While these PR cells were completely refractory to palbociclib, they were significantly more sensitive to BLU-222. Moreover, combining BLU-222 with palbociclib demonstrated a strong synergistic effect in PR cells accompanied by enhanced apoptosis and cell cycle accumulation in G1 or G2/M phases. Consistent with these in vitro findings, combination treatment with BLU-222 (60 mg/kg; b.i.d.) and palbociclib (50 mg/kg; q.d.) or ribociclib (50 mg/kg; q.d.) exhibited significant antitumor activity in all four PDX models, as compared to either treatment alone. The combination of BLU-222 plus the CDK4/6 inhibitor induced durable tumor regression and prolonged survival, which continued unabated following drug removal. Mechanistically, treatment of PR cells and palbociclib-resistant PDX models with BLU-222 as a single agent, resulted in the induction of p21, which can sensitize the cells to palbociclib. Conclusions: These results show robust activity of BLU-222 in combination with CDK4/6 inhibitors in breast cancer cell lines and PDX models resistant to CDK4/6 inhibitors, providing a strong rationale for advancing BLU-222 plus CDK4/6 inhibitor treatment to clinical development in HR-positive/HER2-negative breast cancer patients who have progressed on CDK4/6 inhibitors. Citation Format: Linjie Luo, Juliana Navarro-Yepes, Yan Wang, Tuyen Bui, Nicole Kettner, Debu Tripathy, Kelly Hunt, Kerrie Faia, Khandan Keyomarsi. Combination treatment with CDK2 inhibitor (BLU-222) and either palbociclib or ribociclib is synergistic in pre-clinical models of CDK4/6 inhibitor-resistant breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-18-05.

Evaluating The Cytotoxic Activity of Lactobacillus plantarum IIA-1A5 Against MCF-7 Human Breast Cancer Cells and Identifying Its Surface Layer Protein Gene

Breast cancer is a serious global health concern, with a high mortality rate worldwide. Using natural compounds as potential cancer therapies is a promising approach to address this issue. Previous research has shown that probiotic lactic acid bacteria (LAB) and their metabolites, such as surface layer protein (slp), have a positive impact on a variety of health disorders, including cancer. The purpose of this study was to evaluate the ability of Lactobacillus plantarum IIA-1A5 to suppress the growth of the MCF-7 breast cancer cell line and detect the presence of the slp gene. Intracellular and extracellular protein fractions were isolated from L. plantarum IIA-1A5 cultures. The protein concentrations and molecular weights of the extracts were measured. The anticancer activity of the extracts was assessed using the MTT cytotoxicity test, and IC50 values were calculated. The slp gene was identified through polymerase chain reaction (PCR) amplification and nucleotide sequencing. The results demonstrated that L. plantarum IIA-1A5 had a concentration-dependent inhibitory effect on MCF-7 breast cancer cells, with IC50 values of 6.831 and 12.35 μg/mL for intracellular extracts and extracellular extracts, respectively. Additionally, PCR amplification and nucleotide sequencing confirmed the presence of the slp gene, which may contribute to the strain’s anticancer abilities. These findings suggest the potential of L. plantarum IIA-1A5 as a natural anticancer agent against MCF-7 breast cancer cells. Further research is warranted to elucidate the underlying mechanisms of L. plantarum IIA-1A5 in breast cancer treatment.

Antibacterial activity, cytotoxicity and chemotaxonomic significance of chemical constituents from Alsophila manniana Hook R.M.Tryon (Cyatheaceae) rhizomes

Phytochemical investigation of Alsophila manniana rhizomes led to the isolation of twelve known compounds, including two triterpenes (1 and 2), four steroids (3–6), one glycerol (7), three phenols (8–10), and two flavonoids (11 and 12). Their structures were elucidated by analyses of the NMR and MS data and by comparisons with those in the literature. Their antibacterial and cytotoxic activities were evaluated against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Bacillus subtilis; and on human lung A549, cervical HeLa, and breast MCF-7 cancer cell lines, respectively. Fractions FD and FF had significant activities against E. coli (MIC = 75 μg/mL) and K. pneumoniae (MICs = 75 and 37.5 μg/mL). Compounds 3 and 7–12 had moderate antibacterial activities with MIC values ranging from 75 to 150 μg/mL against the bacteria. All samples were inactive against all tested human cancer cell lines, even at 100 μg/mL. This is the first investigation of the chemical constituents of A. manniana, as well as the first report of compounds 3, 7, and 10–12 from the genus Alsophila. The chemotaxonomic significance of these compounds is discussed.

Highly sensitive ratiometric fluorescent fiber matrices for oxygen sensing with micrometer spatial resolution

AbstractOxygen (O2)-sensing matrices are promising tools for the live monitoring of extracellular O2 consumption levels in long-term cell cultures. In this study, ratiometric O2-sensing membranes were prepared by electrospinning, an easy, low-cost, scalable, and robust method for fabricating nanofibers. Poly(ε-caprolactone) and poly(dimethyl)siloxane polymers were blended with tris(4,7-diphenyl-1,10-phenanthroline) ruthenium(II) dichloride, which was used as the O2-sensing probe, and rhodamine B isothiocyanate, which was used as the reference dye. The functionalized scaffolds were morphologically characterized by scanning electron microscopy, and their physicochemical profiles were obtained by Fourier transform infrared spectroscopy, thermogravimetric analysis, and water contact angle measurement. The sensing capabilities were investigated by confocal laser scanning microscopy, performing photobleaching, reversibility, and calibration curve studies toward different dissolved O2 (DO) concentrations. Electrospun sensing nanofibers showed a high response to changes in DO concentrations in the physiological-pathological range from 0.5 to 20% and good stability under ratiometric imaging. In addition, the sensing systems were highly biocompatible for cell growth promoting adhesiveness and growth of three cancer cell lines, namely metastatic melanoma cell line SK-MEL2, breast cancer cell line MCF-7, and pancreatic ductal adenocarcinoma cell line Panc-1, thus recreating a suitable biological environment in vitro. These O2-sensing biomaterials can potentially measure alterations in cell metabolism caused by changes in ambient O2 content during drug testing/validation and tissue regeneration processes. Graphic abstract

Effect of sitagliptin on down-regulation of KAT7 and SIRT1 gene expression in breast cancer cell line MCF7

Effect of sitagliptin on down-regulation of KAT7 and SIRT1 gene expression in breast cancer cell line MCF7

Differential Effect of 4H-Benzo[d] [1, 3]oxazines on the Proliferation of Breast Cancer Cell Lines.

A family of 4H-benzo[d][1,3]oxazines were obtained from a group of N-(2-alkynyl)aryl benzamides precursors via gold(I) catalysed chemoselective 6-exo-dig C-O cyclization. The precursors and oxazines obtained were studied in breast cancer cell lines MCF-7, CAMA-1, HCC1954 and SKBR-3 with differential biological activity showing various degrees of inhibition with a notable effect for those that had an aryl substituted at C-2 of the molecules. 4H-benzo[d][1,3]oxazines showed an IC50 rating from 0.30 to 157.4 µM in MCF-7, 0.16 to 139 in CAMA-1, 0.09 to 93.08 in SKBR-3, and 0.51 to 157.2 in HCC1954 cells. We observed that etoposide is similar to benzoxazines while taxol effect is more potent. Four cell lines responded to benzoxazines while SKBR-3 cell line responded to precursors and benzoxazines. Compounds 16, 24, 25 and 26 have the potent effect in cell proliferation inhibition in the 4 cell lines tested and correlated with oxidant activity suggesting a possible mechanism by ROS generation. These compounds represent possible drug candidates for the treatment of breast cancer. However, further trials are needed to elucidate its full effect on cellular and molecular features of cancer.

In vitro cytotoxicity assessment of biosynthesized nanoceria against MCF-7 breast cancer cell lines

Breast cancer poses a significant health concern due to its increasing prevalence and mortality rates. Hence, prompt action is needed to develop innovative therapeutic interventions, as conventional treatments exhibit severe adverse effects and have limited efficacy. This study aims to develop an innovative therapeutic intervention for breast cancer using biosynthesized nanoceria. Nanoceria has gained significant importance in the medicinal field due to its biocompatibility, dual capabilities as both antioxidant and prooxidant, and specific cytotoxicity towards cancer cells. Herein, nanoceria was biosynthesized using Echinochloa frumentaceae grain extract (EFNC) due to its eco-friendly and cost-efficient nature, and it was systematically investigated using standard characterization techniques. Furthermore, their anticancer efficacy against MCF-7 breast cancer cell lines was studied using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell viability assay, and the occurrence of apoptosis was determined using acridine orange/ethidium bromide (AO/EtBr) staining. Significantly, EFNC exhibited superior anticancer efficacy even at lower concentrations (10 µg/mL), and the IC50 value was found at 47.32 µg/mL. In addition, the observed bright green and orange-red fluorescence, along with fragmented/condensed chromatin features in AO/EtBr staining clearly indicated that the EFNC caused cell death through the apoptotic route. One potential factor contributing to the observed anticancer effectiveness of EFNC could be its prooxidant properties within cancer cells. These properties ultimately enhanced oxidative stress, induced the accumulation of reactive oxygen species (ROS), and led to apoptosis. Hence, the in vitro analysis substantiated the significant anticancer efficacy of EFNC, suggesting its potential utility as a promising therapeutic agent in anticancer treatment. These findings pave the way for further exploration and development of EFNC as a valuable candidate for addressing cancer-related challenges.

Structural, theoretical and biological studies on Cu2+ and Co2+ complexes of new thiosemicarbazone ligands

Two sets of Cu2+, and Co2+ complexes of two 4 – Pyridyl thiosemicarbazone derivatives ligands symbolized by (H3L1), and (H3L2), were synthesized and examined utilizing different analytical, and spectroscopic techniques such as (FT-IR, Elemental Analysis, Magnetic studies, PXRD, UV–Vis, and GCMS–). Thermal stability along with kinetic parameters of both Co2+ complexes were studied. 1H NMR technique was used to confirm the structures of both ligands. The proposed geometries of complexes were recognized by density function theory (DFT) calculations using Material software. Additionally, Quantum theory of atoms in molecules (QTAIM) topological analyses for both ligands were obtained using Multiwfn software. The cyclic voltammogram revealed that copper ions are electroactive and exhibited two reduction waves. Fluorescence studies for both ligands showed a direct increase in the intensity of emissions because of increasing Co2+ concentration in solution. Moreover, several biological evaluations were carried out for all six compounds to evaluate their potential use as biological agents, including antioxidant activity using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging approach, anti-microbial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans, DNA degradation activity, in addition to anticancer activity, along with molecular docking theoretical study against MCF-7 breast cancer cell line to determine the compounds ability to act as antitumor. It was found that the investigated compounds (especially the free ligands) have beneficial effects such as antimicrobial, antitumor, and DNA degradation agents. Furthermore, Co2+ complex (2) has the highest ABTS scavenging activity.

Noducyclamides A1-A4, B1, and B2 from the Cyanobacterium Nodularia sp. NIES-3585.

A chemical investigation of the hydrophilic fraction of a cultured Nodularia sp. (NIES-3585) afforded six new cyclic lipopeptides, noducyclamides A1-A4 (1-4) containing 10 amino acid residues and dodecapeptides noducyclamides B1 and B2 (5 and 6). The planar structures of these lipopeptides were elucidated based on the combination of HRMS and 1D and 2D NMR spectroscopic data analyses. These peptides are structurally analogous to laxaphycins and contain the nonproteinogenic amino acids 3-hydroxyvaline and 3-hydroxyleucine and a β-amino decanoic acid residue. The absolute configurations of the noducyclamides (1-6) were determined by acid hydrolysis, followed by advanced Marfey's analysis. Noducyclamide B1 (5) showed cytotoxic activities against MCF7 breast cancer cell lines with an IC50 value of 3.0 μg/mL (2.2 μM).

Alkylide derivatives of diphyllin: synthesis and preliminary anticancer evaluation.

Fourteen diphyllin 4-C-substituted alkylide derivatives were designed and synthesized using a Heck coupling and subsequent hydrogenation reaction. Olefins 3g and 3i exhibited the highest cytotoxicity on breast cancer cell lines MCF-7 with IC50 values of 0.08 and 0.07 µM, and they showed weaker V-ATPase inhibitory potency compared to diphyllin.

New enantioenriched β-indolyl ketones as aromatase inhibitors: Unraveling heme-ligand interactions by MD simulationand MMPBSA analysis.

A series of enantioenriched β-indolyl ketones as aromatase inhibitors (AI) is synthesized through the Michael-type Friedel-Crafts alkylation of indole. A highly efficient bifunctionalized amino catalyst is developed to access structurally diverse β-indolyl ketones in high yields (up to 91%) and excellent enantioselectivity (enantiomeric ratio up to 98:2). All the synthesized compounds demonstrated promising aromatase inhibitory potential, where ortho-substituted analogs (3c and 3e) were found most active with IC50 values of 0.68 and 0.90 µM, respectively. Both of these compounds exhibited significant cytotoxicity (IC50 = 0.34 and 0.37 µM) against the MCF-7 breast cancer cell line in the (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay. Molecular docking studies of the synthesized compounds demonstrate favorable binding interactions with the estrogens controlling CYP19A1 (3EQM) and metabolizing CYP3A4 (5VCC) enzymes. Molecular dynamic (MD) simulation analysis revealed the essentiality of heme-ligand interactions to build a stable protein-ligand complex. An average root mean square deviation of 0.35 nm observed during a 100-ns MD simulation and binding free energy in the range of -190 to -227 kJ/mol calculated by g_mmpbsa analysis authenticated the stability of the 3c-3EQM complex. ADMET and drug-likeness parameters supported the suitability of these indole derivatives as the drug lead to develop potent inhibitors for estrogen-dependent breast cancer.

Assessment of the cytotoxic effect of carboxymethyl chitosan-loaded amygdalin nanoparticles against human normal and cancer cell lines

In recent years, the development of antitumor drugs has been dedicated to natural products. Amygdalin is a natural herbal cyanoglycoside that has anticarcinogenic effect on many types of cancers once hydrogen cyanide (HCN) is released. The main objective of the present study is to synthesize and investigate the potential of carboxymethyl chitosan nanoparticles (CMC NPs) as drug delivery agents for amygdalin encapsulation and its delivery to cancer and normal cell lines. In this study, carboxymethyl chitosan nanoparticles encapsulated with amygdalin (CMC-Am NPs) were prepared and characterized through their particle size, surface charge, chemical structure and dielectric properties. Also, the invitro drug release of amygdalin from CMC NPs was studied. Additionally, the cytotoxcity of the amygdalin and CMC-loaded amygdalin NPs were evaluated through MTT assay. The results showed that the prepared CMC-loaded amygdalin NPs exhibited a small particle size of 129 nm, high zeta potential value of − 43 mV and confirmed the amygdalin stability and compatibility with CMC NPs. Furthermore, the CMC NPs demonstrated sustained release of amygdalin during 24 h. Moreover, compared to free amygdalin, amygdalin-loaded CMC NPs have significant anti-cancerous effect on human colon HCT-116 and breast MCF-7 cancer cell lines while being safe on normal cells BJ1. In conclusion, CMC NPs can be employed as an efficient drug delivery vehicle for controlled and sustained amygdalin release with enhanced cytotoxicity on malignant cells without harming normal cells.

Design, synthesis and molecular docking of novel 4-morpholino-1H-pyrrolo[2,3-b] pyridine-5-carboxamides and 4-methylpiperazin-1H-pyrrolo[2,3-b] pyridine-5-carboxamides for the evaluation anti-cancer activity

A novel series of 4-morpholino-1H-pyrrolo[2,3-b] pyridine-5-carboxamides (6 a-j) and 4-methylpiperazin-1H-pyrrolo[2,3-b] pyridine-5-carboxamides (9 a-i) have been designed and synthesized. All the synthesized compounds were well characterized and screened for their anti-cancer activity against MCF-7 breast cancer cell lines and A549 Lung cancer cell lines. The result of this study discloses that the synthesized compounds were shown good to moderate activity. The IC50 values of the tested compounds against MCF-7 cell lines are ranged from 16-111.9µg/mL. Whereas the IC50 values of the tested compounds against A-549 cancer cell line are ranged from 21-115.3 µg/mL. Among, the synthesized compounds, 6h exhibited significant cytotoxic activity against MCF-7 and A-549 with IC50 16µg/mL and 21µg/mL respectively. Based on the in vitro cytotoxic activity results, compound 6h and 9i showed good activity. Molecular docking experiments were conducted for 6h and 9i with EGFR (PDB ID-4HJO). Among these two, 6h has exhibited the highest binding energy (-11.22 kcal/mol) and 9i has exhibited remarkable binding energy (-8.06 kcal/mol).

Investigations of Ni(II)Cysteine-Tyrosine Dithiocarbamate Complex: Synthesis, Characterization, Molecular Docking, Molecular Dynamic, and Anticancer Activity on MCF-7 Breast Cancer Cell Line.

Breast cancer ranks second in terms of the highest number of cancer deaths for women worldwide and is one of the leading causes of death from cancer in women. The drug that is often used for chemotherapy is cisplatin. However, cisplatin drugs have a number of problems, including lack of selectivity, unwanted side effects, resistance, and toxicity in the body. In this work, we investigated Ni(II) cysteine-tyrosine dithiocarbamate complex against breast cancer. Research on the new complex compound Ni(II) cysteine-tyrosine dithiocarbamate have several stages including synthesis, characterization, in-silico and in-vitro testing of MCF-7 cells for anticancer drugs. The synthesis involved reacting cysteine, CS2, KOH and tyrosine with Mn metal. The new complex compound Ni(II) cysteine-tyrosine dithiocarbamate has been synthesized, characterized, and tested in vitro MCF-7 cells for anticancer drugs. Characterization tests such as melting point, conductivity, SEM-EDS, UV Vis, XRD, and FT-IR spectroscopy have been carried out. The synthesis yielded a 60,16%, conversion with a melting point of 216-218 oC and a conductivity value of 0.4 mS/cm. In vitro test results showed morphological changes (apoptosis) in MCF-7 cancer cells starting at a sample concentration of 250 µg/mL and an IC50 value of 618.40 µg/mL. Molecular docking study of Ni(II) cysteine-tyrosine dithiocarbamate complex identified with 4,4',4''-[(2R)-butane-1,1,2-triyl]triphenol - Estrogen α showing active site with acidic residue amino E323, M388, L387, G390 and I389. Hydrophobic and hydrophobic bonds are seen in Ni(II) cysteine-tyrosine dithiocarbamate - Estrogen α has a binding energy of -80.9429 kJ /mol. there were 5 residues responsible for maintaining the ligand binding stable. The compound had significant Hbond contact intensity, however, it was not strong enough to make a significant anticancer effect. Though the synthesized compound shows low bioactivity, this research is expected to give valuable insight into the effect of molecular structure on anticancer activity.