Breast Cancer Cell Line MCF-7 Research Articles

Synthesis and characterization of biocompatible quaternized chitosan-coated magnetite-maghemite nanoparticles

In this work, we present the process of synthesis, characterization and evaluation of biocompatibility of aqueous suspensions of magnetite-maghemite nanoparticles stabilized with quaternized chitosan. The nanocomposites were obtained by the coprecipitation method of Fe2+ and Fe3+ species in a quaternized chitosan solution. Chemical, structural, morphological and magnetic analyses confirmed that the nanocomposites synthesized are composed of magnetite-maghemite nanoparticles coated by quaternized chitosan chains with positive surface charge, giving them a good colloidal stability. The potential cytotoxic effect of the nanocomposite’s suspension was determined using both MTT and alamarBlue viability assays in cultures of the murine macrophage cell line J774 and the breast cancer cell line MCF-7. The results show that, after 24 h of incubation, J774 cells treated with nanocomposites with iron contents up to 100 ppm and MCF-7 cells treated with nanocomposites with iron contents up to 30 ppm presented both a viability above 70 %. Our results support the hypothesis that the synthesized aqueous suspensions of magnetic nanocomposites are biocompatible, which opens a door to their use in future biomedical applications.

DFT and molecular docking research on the effects of lichen metabolites

Breast cancer remains a significant public health problem worldwide and requires the investigation of new treatment methods. Lichens, symbiotic organisms rich in bioactive compounds, have emerged as promising sources of natural anticancer agents. This study investigates the anticancer effects of lichen metabolites derived from Xanthoparmelia wyomingica on breast cancer cell lines MCF-7 and MDA-MB231. High-performance liquid chromatography (HPLC) was used to measure specific lichen acids in the extract; this revealed the presence of Gyrophoric acid (GA), Norstictic acid (NA), Protocetraric acid (PA), Stictic acid (SA), and Usnic acid (UA). Cytotoxicity analysis showed significant reductions in cell viability, particularly in the MDA-MB231 cell line, with IC50 values ranging from 21.67 to 36.71 µg/mL. Molecular docking studies elucidated the interaction mechanisms between these metabolites and target proteins, highlighting NA as the most promising compound with the lowest binding energy (−9.5 kcal/mol) and inhibition constant (0.108755 μM). ADMET analysis of the molecules was then performed. Molecular electrostatic potential (MEP) and HOMO-LUMO analysis provided further information about the reactivity and electron distribution of the compounds. This study has the potential to provide novel therapeutic agents for breast cancer to tackle the increasing resistance to conventional therapies. Lichen metabolites enable the development of effective therapies in targeting aggressive subtypes such as triple-negative breast cancer with limited treatment options. This research highlights the anticancer properties of lichen metabolites and their potential in the development of innovative strategies for breast cancer treatment. The findings offer a promising avenue to address the urgent need for effective therapies in oncology.

Synergistic anticancer efficacy of polydatin and sorafenib against the MCF-7 breast cancer cell line via inhibiting of PI3K/AKT/mTOR pathway and reducing resistance to treatment

Polydatin (PD), a glucoside derivative of resveratrol, has been investigated for its potential to mitigate sorafenib (SOF) side effects and combat multidrug resistance in cancer treatment. The study evaluated its mechanism of action for inhibiting the protein kinase B/mTOR pathway in promoting breast cancer proliferation. The combined PD and SOF have synergistic effects with a combination index (CI) < 1 in the liver (HepG2) and breast (MCF-7) cancer cell lines. Molecular docking studies were conducted to analyze interactions of PD& SOF with protein kinases as well as apoptotic and multidrug resistance proteins, including AKT1, PI3K, mTOR, Apaf-1, and ABCB1 in MCF-7 cells. Experimental validation through real-time PCR confirmed. PD has a strong binding affinity, particularly with AKT1 (-56 kcal/mol) and ABCB1 (-27.16 kcal/mol), a gene associated with multidrug resistance. These interactions were linked to anti-proliferative anti-angiogenic effects and reduced resistance to treatment, demonstrating PD has potential therapeutic benefits. Furthermore, PD combined with SOF induced apoptosis, inhibited cell growth, and arrested MCF-7 cells in the sub-G1 phase with increased intracellular ROS. This was accompanied by reduced expression of AKT1 and ABCB1 genes, reinforcing the anticancer efficacy of PD/SOF combination therapy. In conclusion, the findings suggest that PD/SOF could serve as a promising anticancer treatment strategy, warranting further investigation for potential clinical applications and mechanistic studies in vivo.

Characterization of a drug resistant MCF-7 breast cancer cell line developed by repeated cycles of 5-Fluorouracil (5-FU) therapy

Breast cancer accounts for 14% of cancer fatalities and 23% of all cancer diagnoses, making it the most common cause of cancer death among women and one of the most frequently diagnosed cancers. This disease is a life-threatening public health concern because of its significant influence on the general population. Therefore, further molecular research is required to determine its prognosis and create tailored treatments. Since it closely resembles mammary epithelium, the human breast cancer cell line MCF-7, which expresses genes for oestrogen, progesterone, and glucocorticoid receptors, is the most appropriate in vitro model for cancer research. Resistant cell lines were created by repeatedly cultivating MCF-7 wild-type cells in media containing 5-fluorouracil, a first-line treatment for breast cancer. The resistant cell lines were found to be cross-resistance to other anticancer medications in addition to being resistant to 5-fluorouracil, according to the in vitro MTT cytotoxicity assay.

Green synthesis and anticancer activity of titanium dioxide nanoparticles using the endophytic fungus Aspergillus sp.

Titanium dioxide nanoparticles (TiO2 NPs) have attracted significant attention for their unique physicochemical features and various applications. This study demonstrated the biosynthesis of TiO2 NPs using Aspergillus fungal extract that served as a green and eco-friendly reducing and stabilizing agent. The biosynthesized nanoparticles were analyzed using SEM and TEM to determine their morphology, size, and distribution, FTIR to determine functional groups, and Zeta potential to assess their surface charge and stability. An extensive review of the Protein Data Bank (PDB) and literature indicated that TiO2 could target various cancer-relevant matrix metalloproteinases. In vitro screening indicated promising anticancer effects against the MCF7 breast cancer cell line. To investigate the possible mode of action of TiO2 NPs as an anticancer agent, human matrix metalloproteinase-3 was highlighted as a protein inhibited by metallic ions like PtCl2. Therefore, we investigated whether TiO2 could similarly interact with the active site of MMP-3. We hypothesized that TiO2 could interact with the MMP-3 active site and replace PtCl2 with modelled TiO2 in its co-crystallized binding site. A 100 ns-long MDS, binding free energy (ΔGBinding) of PtCl2 and TiO2 within MMP-3 binding site indicated that TiO2's enhanced binding affinity and stability, as evidenced by a ΔGBinding of −7.23 kcal/mol and average RMSD of 0.89 Å, compared to PtCl2's lower affinity. In conclusion, endophytic fungi can be used efficiently in the biosynthesis of nanoparticles. Our study indicated TiO2 NPs have a potential anticancer effect, suggesting TiO2 binds to MMP3, potentially offering comparable inhibitory effects on the enzyme's activity.

New Carrageenan/2-Dimethyl Aminoethyl Methacrylate/Gelatin/ZnO Nanocomposite as a Localized Drug Delivery System with Synergistic Biomedical Applications

In recent years, the development of multifunctional hydrogels has gained significant attention due to their potential in various biomedical applications, including antimicrobial, antioxidant, and anticancer therapies. By integrating biocompatible polymers and nanoparticles, these hydrogels can achieve enhanced activity and targeted therapeutic effects. In this study, carrageenan/2-dimethyl aminoethyl methacrylate/gelatin (CAR/DEMA/Gelt) composite hydrogel was synthesized using microwave radiation specifically for its efficiency in enhancing cross-linking and promoting uniform nanoparticle dispersion within the matrix. Zinc oxide (ZnO) nanoparticles were incorporated into the hydrogel to form the (CAR/DEMA/Gelt/ZnO) nanocomposite. The hydrogels were characterized using FT-IR, FE-SEM, XRD, TGA, and EDX, confirming successful cross-linking and structural integrity. The nanocomposite hydrogel exhibited more enhanced antimicrobial activity than the composite hydrogel against Gram-positive Staphylococcus aureus (S. aureus) and Bacillus subtilis (B. subtilis), with inhibition zones of 15 mm and 16 mm, respectively, while in case of the Gram-negative bacteria, Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli), the inhibition zones were 29 mm and 19 mm, respectively. In addition to the unicellular fungi, Candida albicans (C. albicans), the inhibition zone was 19 mm. Moreover, the nanocomposite showed anti-inflammatory activity comparable to those of Indomethacin and antioxidant activity, with an impressive IC50 value of 33.3 ± 0.05 µg/mL. In vitro cytotoxicity assays revealed significant anticancer activity. Against the MCF-7 breast cancer cell line, the CAR/DEMA/Gelt/ZnO nanocomposite showed 72.5 ± 0.02% cell viability, which decreased to 30.8 ± 0.01% after loading doxorubicin (DOX). Similarly, against the HepG2 liver cancer cell line, the free nanocomposite displayed 59.9 ± 0.006% cell viability, which depleted to 29.9 ± 0.005% when DOX was uploaded. This CAR/DEMA/Gelt/ZnO nanocomposite hydrogel demonstrates strong potential as a multifunctional platform for targeted biomedical applications, particularly in cancer therapy.

New metal complexes of 1H-benzimidazole-2-yl hydrazones: Cytostatic, proapoptotic and modulatory activity on kinase signaling pathways

The copper complexes of two 1H-benzimidazole-2-yl hydrazones were obtained by complexation with copper chloride. The molecular structure of the complexes was studied by microchemical analysis, SEM-EDX, IR and micro-Raman spectroscopy and DFT calculations. It was found that both ligands form 1:1 complexes with the copper, where the Cu ions are coordinated by N-atom from the benzimidazole ring, N-atom of the azomethine bond, O-atom from the ortho-OH group of the aromatic ring and one chlorine atom. The coordination process significantly affected their cytotoxicity profile. The conversion of 2-(2-hydroxybenzylidene)-1-(1H-benzimidazol-2-yl)hydrazine 1.1. into a Cu complex 2.1. led to a 2.4-fold increase in its antileukemic activity against AR-230 cells and an 8-fold increase in the cytostatic activity against MCF-7 breast cancer cell line. The growth-inhibitory effect of the Cu complex of 2-(2-hydroxy-4-methoxybenzylidene)-1-(1H-benzimidazol-2-yl)hydrazine 2.2. on the MCF-7 cells was comparable to that of the respective ligand, however lacked towards the leukemic AR-230 cell population. Regarding their cytotoxic potential towards CCL-1 cells, both Cu complexes exhibited a weaker selectivity pattern as compared to their ligands. The proapoptotic and modulatory activity of 1.1 and 2.1. on key kinase signaling pathways was further studied in the ER + breast cancer (MCF-7) and bcr-abl + leukemic (AR-230) in vitro tumor models in a comparative manner to the reference drugs tamoxifen and imatinib, respectively. Inhibition of the JAK/STAT signaling pathway was outlined as a prominent mechanism in the antileukemic activity against the Ph + AR-230 in vitro model, whereas recruitment and activation of the extrinsic apoptotic pathway was established in the MCF-7 cells.

Investigation of anticancer potential of a novel bioactive molecule from Trichosporon asahii VITSTB1 in breast cancer cell lines: an in vitro study.

The current study investigates the anticancer activity of protein derived from yeast against breast cancer. Yeast-derived proteins illustrate potential as an anticancer agent through mechanisms, such as immune system stimulation via beta-glucans, cytotoxic effects, and modulation of gut microbiota by probiotic strains. The antioxidant activity of yeast-derived proteins can aid in anticancer activity by neutralizing free radicals, thereby reducing oxidative stress and preventing damage to cellular DNA. Employing a comprehensive methodology encompassing yeast isolation, antioxidant screening, molecular characterization, bioactive protein purification, and MTT assay, the research provides crucial insights into the anticancer attributes of the protein extracted from the yeast. The findings reveal significant antioxidant activity that reduces reactive oxygen species (ROS) levels, which are implicated in cancer development. The MTT assay on MCF-7 breast cancer cell lines, characterized by estrogen receptor and progesterone receptor positivity and HER-2 negativity, determined an IC50 value of 54.89µg/ml, indicating a dose-dependent decrease in cytotoxic effects. These results suggest that the protein derived from Trichosporon asahii VITSTB1 exhibits promising anti-breast cancer properties. Further research is necessary to elucidate the underlying mechanisms, assess efficacy and safety profiles, explore synergies with existing therapies, and conduct animal model studies. Advancing this line of inquiry will significantly contribute to biomedical research and industrial innovation.

Synthesis, characterization, cytotoxic activity, and molecular docking of 3,4-diaminobenzophenone-CuhNFs and its major components-based nanoflowers

In this study, organic–inorganic hybrid nanoflower (hNFs) synthesis was realized using 3,4-diaminobenzophenone and Cu(II) metal ions as organic and inorganic ingredients, respectively. The characterization of the synthesized hNFs was carried out using SEM, EDX, FT-IR, XRD, and elemental mapping. The cytotoxic effect of hNFs was investigated against A549 (lung) and MCF-7 (breast) cancer cell lines. Interactions of 3,4-diaminobenzophenone were also investigated via molecular docking studies at the binding site of the human estrogen receptor (PDB ID:3ERT) and epidermal growth factor receptor tyrosine kinase (PDB ID: 1M17). Physicochemical and pharmacokinetic parameters for ligands that could be potential anticancer drug candidates were determined by ADME prediction calculations from in silico approaches. In vitro results showed an increase in cell death when the synthesized hybrid nanoflowers were applied against both cell lines, depending on the concentrations tested. Additionally, it was determined that the synthesized nanoflower was more effective on the MCF-7 cell line.

Synthesis, mechanistic insights, and anticancer evaluation of novel 2-aroylbenzo[b]thiophen-3-ols: A DFT and Hirshfeld surface analysis

A simple one-pot reaction was employed for the synthesis of 2-aroylbenzo[b]thiophene derivatives by reacting 2-mercaptobenzoic acid with substituted bromomethyl aryl ketones in the presence of triethylamine and DMF in significant yield and purity. The structure of the product was elucidated through spectroscopic data and confirmed through single crystal X-ray diffraction data. The benzo[b]thiophene ring was found to be nearly coplanar with the adjacent carbonyl group and conformationally stabilized by intramolecular hydrogen bonding. The key intramolecular cyclization takes place via an in-situ generated enol, which is most likely formed and reacts at the carboxylic group mediated by the conjugate acid, triethylammonium bromide. Density functional theory (DFT) was employed to investigate the energy profile of the reaction at the B3LYP/6–31G(d,p) level. Finally, all the synthesized 2-aroylbenzo[b]thiophene-3-ols were screened in vitro against HCT116 (colorectal) and MCF-7 (breast) cancer cell lines at 25 μM and 50 μM treatments, indicating the antiproliferative potential of several derivatives.

Bromelain augments ionizing radiation sensitivity in breast cancer cells: A synergistic approach

BackgroundRadiation-sensitizing agents, such as Bromelain (pineapple extract) have been shown to significantly impact cancer cell cycle arrest. This study investigates the anticancer properties of Bromelain on MCF-7 breast cancer cell line under both two-dimensional (2D) and three-dimensional (3D) culture conditions. MethodsBromelain enzyme was initially applied at concentrations of 75, 96, and 115 μg/ml to sensitize the MCF-7 cells under both 2D and 3D culture conditions. Following treatment, the cells were irradiated with doses of 2, 4, and 6 Gy. The synergistic effects of bromelain enzyme treatment and gamma irradiation on MCF-7 cells were assessed using the MTT assay, neutral red uptake assay, alkaline comet assay, nitric oxide (NO) release measurement, catalase activity assay, reduced glutathione quantification, and caspase 3 assay. Data were analyzed and presented as Mean ± SD using GraphPad InStat software V. 8. ResultsThe MTT assay indicated that the combination of bromelain and ionizing radiation have synergistic effects compared to cells treated with 2 Gy of X-ray alone. The results from of the MTT assay indicated showed that 75 μg/ml of bromelain did not induce exhibit significant cytotoxicity. Consistent with the MTT assay results, the Neutral red uptake assay demonstrated increased mortality in MCF-7 cells following treatment with both bromelain and ionizing radiation. Additionally, treatment with bromelain and ionizing radiation resulted in elevated levels of released NO, GSH content, and catalase enzyme activity compared to cells treated with bromelain alone. Furthermore, the Combination of ionizing radiation and bromelain synergistically enhanced caspase-3 enzyme activity and increased the number of necrotic and apoptotic cells compared to treatment with bromelain alone. ConclusionBromelain's capacity to induce apoptosis and enhance radio-sensitization offers promising potentialfor improving cancer treatment outcomes. By promoting programmed cell death and increasing the sensitivity of cancer cells to radiation, bromelain could contribute to more effective treatment regimens while potentially reducing the adverse effects associated with more aggressive therapies.

Cytotoxic activity of water and ethanol extract of Curcuma caesia (black turmeric) on breast cancer cell line

Breast cancer is one of the cancers with the highest incidence and mortality rate in the world. Curcuma caesia (Black turmeric) is known to have neuroprotective, anthelmintic, sunscreen activity, anti-diabetic and also anti-cancer activity. This study aimed to determine the phytochemical content and possible cytotoxic activity of C. caesia water extract (EWCC) and C. caesia ethanol extract (EECC) on breast cancer cell lines. Samples were extracted using two extraction methods, maceration technique using 96% ethanol as solvent and double boiling using water as a solvent. The phytochemical content, total phenolic content (TPC), and total flavonoid content (TFC) of each extract were determined using spectrophotometer method. Cytotoxic activity was measured using MTT assay on MCF-7 and 4T1 breast cancer cell lines (24 hrs and 48 hrs). Results showed that EWCC and EECC contained flavonoids, alkaloids, and polyphenols. The values of TPC and TFC were 106.08 mg GAE/100 g and 4.32 mg QUE/g for EECC, respectively, and 73.29 mg GAE/100 g and 3.40 mg QUE/g for EECC, respectively. Meanwhile, the cytotoxic activity test found that EWCC did not provide cytotoxic activity on MCF-7 and 4T1 cells. In the MCF-7 cell line, EECC exhibited IC50 values of 212.90 µg/mL at 24 hrs and 311.91 µg/mL at 48 hrs. Similarly, in the 4T1 cell line, EECC exhibited IC50 values of 161.06 µg/mL at 24 hrs and 150.89 µg/mL at 48 hrs. From these results, it can be concluded that EECC has cytotoxic activity in MCF-7 and 4T1 breast cancer cell models, so this extract can be studied more deeply to determine its pathway of action.

Insight on novel sulfamoylphenyl pyrazole derivatives as anticancer carbonic anhydrase inhibitors.

As another part continue for our previous study, variable substituted pyrazoles bearing sulfamoylphenyl moiety were synthesized and screened against two cancer related human carbonic anhydrase (hCA) isoforms and acetazolamide (AAZ) used as a reference standard. Some compounds as 4e and 6c manifested a promising inhibitory activity against both isoforms (KI = 0.072, 0.081 and 0.073, 0.095 µM), respectively. While others as 4a and 5e showed inhibitory activity against hCA IX only (KI = 0.062, 0.04 µM) or against hCA XII only as compound 5b (KI = 0.106 µM) compared to AAZ (KI = 0.065, 0.046 µM), respectively. Also, the anticancer efficacy against 60 cancer cell lines for the target compounds was assessed, and the most promising ones were 4d and 5a-d. Further investigation of the anticancer activity of 5b on MCF-7 cell line explored (IC50 = 5.21 µM) compared to doxorubicin (IC50 = 11.58 µM). Moreover, compound 5b was exposed to cell cycle analysis and apoptotic assay on MCF-7 breast cancer cell line under both normal and hypoxic conditions at its IC50 concentration with elevation of total apoptotic cells % in MCF-7 relative to the control cells; respectively. Finally, molecular modelling simulations rationalized the in vitro testing results.

The impact of hsa-miR-1972 on the expression of von Willebrand factor in breast cancer progression regulation.

Breast cancer (BC) is one of most frequent female malignancies that poses multiple challenges in treatment and prevention. This study aimed to explore the role of miRNAs and their target genes during the BC progression. Based on the BC data (113 normal and 1,118 tumor samples) from the TCGA-BRCA dataset, a single-sample gene set enrichment analysis (ssGSEA) was applied to calculate the cancer migration scores, and weighted gene co-expression network analysis (WGCNA) were performed using the WGCNA R package, with a focus on the set of genes associated with cancer migration. Key modules and hub genes related to cell migration and signaling pathways were identified. Survival analysis of hub genes was conducted using the survminer R package, and prediction of regulatory miRNAs were performed to analyze their impact on BC prognosis. In addition, the BC cell lines MCF-7 and MDA-MB-231 were used to further explore the effect of hsa-miR-1972 mimics on the gene expression and angiogenic factor regulation. The study classified important modules (MEblue, MEmagenta, MEpink, and MEfloralwhite) associated with cell migration and identified three hub genes, namely, MRPL20, COL4A1 and VWF. Survival analysis showed that certain hub genes with a low expression were related to a poor prognosis, whereas low-expressed COL4A1 and VWF were related to better survival outcomes. We also found that hsa-miR-1972 mimics significantly downregulated critical genes involved in BC metastasis and angiogenesis and effectively inhibited the proliferation of BC cell lines, showing a strong therapeutic potential. Manipulation of VWF expression in cells overexpressing hsa-miR-1972 had significant effects on the malignant markers and angiogenic factors, suggesting a novel therapeutic direction for BC treatment. Our study highlighted the complex interplay of genetic factors in BC progression as well as the therapeutic potential of targeting specific miRNAs and their related hub genes. These findings provided novel insights into the pathogenesis of BC and suggested new direction for the therapeutic development for the cancer.

ERα status of invasive ductal breast carcinoma as a result of regulatory interactions between lysine deacetylases KAT6A and KAT6B

Breast cancer (BC) is the leading cause of death among cancer patients worldwide. In 2020, almost 12% of all cancers were diagnosed with BC. Therefore, it is important to search for new potential markers of cancer progression that could be helpful in cancer diagnostics and successful anti-cancer therapies. In this study, we investigated the potential role of the lysine acetyltransferases KAT6A and KAT6B in the outcome of patients with invasive breast carcinoma. The expression profiles of KAT6A/B in 495 cases of IDC and 38 cases of mastopathy (FBD) were examined by immunohistochemistry. KAT6A/B expression was also determined in the breast cancer cell lines MCF-7, BT-474, SK-BR-3, T47D, MDA-MB-231, and MDA-MB-231/BO2, as well as in the human epithelial mammary gland cell line hTERT-HME1 – ME16C, both at the mRNA and protein level. Statistical analysis of the results showed that the nuclear expression of KAT6A/B correlates with the estrogen receptor status: KAT6ANUC vs. ER r = 0.2373 and KAT6BNUC vs. ER r = 0.1496. Statistical analysis clearly showed that KAT6A cytoplasmic and nuclear expression levels were significantly higher in IDC samples than in FBD samples (IRS 5.297 ± 2.884 vs. 2.004 ± 1.072, p < 0.0001; IRS 5.133 ± 4.221 vs. 0.1665 ± 0.4024, p < 0.0001, respectively). Moreover, we noticed strong correlations between ER and PR status and the nuclear expression of KAT6A and KAT6B (nucKAT6A vs. ER, p = 0.0048; nucKAT6A vs. PR p = 0.0416; nucKAT6B vs. ER p = 0.0306; nucKAT6B vs. PR p = 0.0213). Significantly higher KAT6A and KAT6B expression was found in the ER-positive cell lines T-47D and BT-474, whereas significantly lower expression was observed in the triple-negative cell lines MDA-MB-231 and MDA-MB-231/BO2. The outcomes of small interfering RNA (siRNA)-mediated suppression of KAT6A/B genes revealed that within estrogen receptor (ER) positive and negative cell lines, MCF-7 and MDA-MB-231, attenuation of KAT6A led to concurrent attenuation of KAT6A, whereas suppression of KAT6B resulted in simultaneous attenuation of KAT6A. Furthermore, inhibition of KAT6A/B genes resulted in a reduction in estrogen receptor (ER) mRNA and protein expression levels in MCF-7 and MDA-MMB-231 cell lines. Based on our findings, the lysine acetyltransferases KAT6A and KAT6B may be involved in the progression of invasive ductal breast cancer. Further research on other types of cancer may show that KAT6A and KAT6B could serve as diagnostic and prognostic markers for these types of malignancies.

Complementary Treatment of Breast Cancer Cells with Different Metastatic Potential with Iscador Qu in the Presence of Clinically Approved Anticancer Drugs.

European mistletoe extract (Iscador Qu) has been studied for decades, but it has not ceased to arouse scientific interest. The purpose was to investigate the impact of Iscador Qu on the antiproliferative potential of 11 standard chemotherapeutic agents on two breast cancer cell lines: MCF-7 low-metastatic and MDA-MB-231 high-metastatic and control cell lines (MCF-10A). MTT-dye reduction assay, FACS analysis, and PI staining were utilized. The most promising combinations acting against the MDA-MB-231 cell line were observed upon the simultaneous application of Iscador Qu (80 µg/mL) and Docetaxel, with 4-fold reduction in IC50. An antagonistic effect was found under treatment with Cisplatin and Iscador Qu (1.5-fold increase in IC50). The response of the low-metastatic breast cancer cell line MCF-7 to the tested combinations was different compared to the high-metastatic one. The most pronounced cytotoxic effect was found for the combination of Oxaliplatin and Iscador Qu (20 µg/mL) (5.2-fold IC50 reduction). An antagonistic effect for MCF-7 line was also observed when combinations with Olaparib and Tamoxifen were applied. This in vitro study offers new combinations between Iscador Qu and standard chemotherapeutic agents that hold great promise in establishing breast cancer therapeutic protocols compared to traditional monotherapies.

Solvents and their influence on electronic properties in IEFPCM solvation model, anticancer activity, and docking studies on (E)-2-((4-chlorobenzylidene) amino)phenol

The Schiff base (E)-2-((4-chlorobenzylidene)amino)phenol (4CL2AM) has been synthesized from 4-chlorobenzaldehyde and 2-aminophenol. Spectroscopic techniques like FTIR, Raman, UV, fluorescence, and NMR were used to characterize the synthesized compound. The experimental data well matched with the DFT method (B3LYP/cc-pVDZ basis set). The frontier molecular orbital (FMO), molecular electrostatic potential (MEP), and electronic spectra (UV–visible) analysis were conducted on three different solvents such as gas, DMSO, and water. The frontier molecular orbital (FMO) analysis calculated the HOMO-LUMO energy gap as 4.0109 eV, 4.0406 eV, and 4.0411 eV for the gas phase, DMSO, and water respectively. Molecular electrostatic potential (MEP), localized orbital locator (LOL), and electron localize function (ELF) analysis revealed positions of localized and delocalized orbitals as well as electrophilic and nucleophilic attack sites. The natural bond orbital analysis (NBO) predicted highest stabilization energy was 33.37 kcal/mol. The locations of the covalent and non-covalent interactions were investigated by density overlaps region indicator (DORI), interaction region indicator (IRI), and noncovalent interaction (NCI) analysis. Drug likeness and ADME analysis were investigated. In vitro, anticancer activity studies revealed against MCF-7 breast cancer cell lines. In the molecular docking study, the predicted lowest binding energy is −5.77 kcal/mol for the 6NLV-4CL2AM system.

Arene Ruthenium Complexes Specifically Inducing Apoptosis in Breast Cancer Cells

Monocationic arene ruthenium complexes (RuL1–RuL4) incorporating phenothiazinyl-hydrazinyl-thiazole ligands (L1–L4) have been synthesized, characterized and evaluated as anticancer agents. Their cytotoxicity, antiproliferative activity and alteration of apoptotic gene expression were studied on three cancer cell lines, a double positive breast cancer cell line MCF-7 and two triple negative breast cancer cell lines Hs578T and MDA-MB-231. All arene ruthenium complexes were able to reduce the viability of the breast cancer cell lines, with the highest cytotoxicities being recorded for the [(p-cymene)RuL3Cl]+ (RuL3) complex on the MCF-7 (IC50 = 0.019 µM) and Hs578T cell lines (IC50 = 0.095 µM). In the double positive MCF-7 breast cancer cells, the complexes [(p-cymene)RuL1Cl]+ (RuL1) and [(p-cymene)RuL2Cl]+ (RuL2) significantly upregulated pro-apoptotic genes including BAK, FAS, NAIP, CASP8, TNF, XIAP and BAD, while downregulating TNFSF10. In the triple negative breast cancer cell line Hs578T, RuL1 reduced TNFSF-10 and significantly upregulated BAK, CASP8, XIAP, FADD and BAD, while complex RuL2 also increased BAK and CASP8 expression, but had limited effects on other genes. The triple negative MDA-MB-231 cancer cells treated with RuL1 upregulated NOD1 and downregulated p53, while RuL2 significantly downregulated p53, XIAP and TNFSF10, with minor changes in other genes. The significant alterations in the expression of key apoptotic genes suggest that such complexes have the potential to target cancer cells.

Synthesis of S-alkylated oxadiazole bearing imidazo[2,1-b]thiazole derivatives targeting breast cancer: In vitro cytotoxic evaluation and in vivo radioactive tracing studies

Breast cancer is the most common invasive cancer diagnosed in women, accounting for most cancer-related fatalities globally. Numerous investigations have revealed that breast cancer is characterized by abnormal expression and maintenance of EGFR levels. In terms of structural study and optimization of several EGFR inhibitors, two series of oxadiazole bearing imidazo[2,1-b]thiazole derivatives were designed and synthesized as potential EGFR inhibitors and assessed for their antitumor activity at NCI-USA. Four derivatives 3b, 3c, 3d and 3e elicited remarkable GI% against MDA-MB-468, T-47D and MCF-7 breast cancer cell lines. Thereafter, MTT assay was performed to reveal that compounds 3b (IC50 = 2.27 µM) and 3d (IC50 = 1.46 µM) showed promising cytotoxic activity against MCF-7 and MDA-MB-468 cell lines, respectively, compared to their reference drugs. Compounds 3b, 3d and 3e revealed good selectivity toward tumor cells with reasonable safety profile when tested against the normal cell line MCF-10a. In vitro EGFR inhibitory assay demonstrated that compounds 3b (IC50 = 0.099 µM) and 3d (IC50 = 0.086 µM) exhibited comparable inhibitory activity to the standard drug erlotinib (IC50 = 0.046 µM). A flow cytometric analysis demonstrated that derivatives 3b and 3d arrested the cell cycle at the S phase in MCF-7 and MDB-MB-468, respectively. Furthermore, the most active derivative 3d was subjected to in vivo radioactive studies. In-vivo biodistribution of 99mTc-3d complex showed a notable elevated accumulation in the targeted sarcoma muscle, indicating the targeting capacity of compound 3d in the tumor of sarcoma mice model. The binding mode of compounds 3b and 3d with EGFR was studied by molecular docking and was further inspected by molecular dynamic simulations. Both compounds were shown to be stable during the course of simulation and demonstrated a plausible interaction pattern with the EGFR binding pocket.

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.