Search

Aim: Breast cancer is the most common malignancy in women. This disease is a critical public health problem and further research at the molecular level would define its prognosis and specific treatment. Phenformin is an antidiabetic agent. Recent studies showed that it should be considered as a potential agent for the prevention and treatment of cancer cell lines. This study aimed to investigate the antiproliferative effect of phenformin on MDA-MB-231 and MCF-7 breast cancer cell lines. Materials and Methods: MDA-MB-231 and MCF-7 breast cancer cell lines were used in the study. Experimental groups; control group, 1 μM, 2.5 μM, and 5 μM phenformin administered groups were planned. WST-1 analysis was performed to evaluate the viability of cells 24 h after the treatments. Statistical analysis was carried out using the SPSS 17.0 statistical program. p<0.05 was considered to indicate a statistically significant difference. Results: In the MDA-MB-231 breast cancer cell line, there were statistically significant differences among all groups (p<0.05, for all), except between the 1 μM phenformin-treated and control groups (p>0.05). In the MCF-7 breast cancer cell line; there were statistically significant differences between the control group and 5 μM phenformin-treated, and between 1 μM phenformin-treated and 5 μM phenformin-treated (p<0.05, for all) groups. Conclusion: Phenformin seems to exert antiproliferative effects on MDA-MB-231 and MCF-7 breast cancer cell lines. It was observed that the antiproliferative effect was stronger in the MDA-MB-231 cell line. It showed a stronger antiproliferative effect in the MDAMB-231 cell line of antiproliferative effect. [ABSTRACT FROM AUTHOR]

Oestrogen related receptor α participated in the regulation of oxidative metabolism and mitochondrial biogenesis, and was overexpressed in many cancers including triple-negative breast cancer. A set of new ERRα inverse agonists based on p-nitrobenzenesulfonamide template were discovered and compound 11 with high potent activity (IC50 = 0.80 &#191'M) could significantly inhibit the transcription of ERRα-regulated target genes. By regulating the downstream signalling pathway, compound 11 could suppress the migration and invasion of the ER-negative MDA-MB-231 cell line. Furthermore, compound 11 demonstrated a significant growth suppression of breast cancer xenograft tumours in vivo (inhibition rate 23.58%). The docking results showed that compound 11 could form hydrogen bonds with Glu331 and Arg372 in addition to its hydrophobic interaction with ligand-binding domain. Our data implied that compound 11 represented a novel and effective ERRα inverse agonist, which had broad application prospects in the treatment of triple-negative breast cancer. [ABSTRACT FROM AUTHOR]

Background: Sex-determining region Y-box 3 (SOX3) protein, a SOX transcriptions factors group, has been identified as a key regulator in several diseases, including cancer. Downregulation of transcriptions factors in invasive ductal carcinoma (IDC) can interfere in neoplasia development, increasing its aggressiveness. We investigated SOX3 protein expression and its correlation with apoptosis in the MDA-MB-231 cell line, as SOX3 and Pro-Caspase-3 immunoexpression in paraffin-embedded invasive ductal carcinoma tissue samples from patients (n = 27). Breast cancer cell line MDA-MD-231 transfected with pEF1-SOX3 + and pEF1-Empty vector followed by cytotoxicity assay (MTT), Annexin-V FITC PI for apoptosis percentage assessment by flow cytometry, qPCR for apoptotic-related gene expression, immunofluorescence, and immunohistochemistry to SOX3 immunolocalization in culture cells, and paraffin-embedded invasive ductal carcinoma tissue samples.Results: Apoptotic rate was higher in cells transfected with pEF1-SOX3 + (56%) than controls (10%). MDA-MB-231 transfected with pEF1-SOX3 + presented upregulation of pro-apoptotic mRNA from CASP3, CASP8, CASP9, and BAX genes, contrasting with downregulation antiapoptotic mRNA from BCL2, compared to non-transfected cells and cells transfected with pEF1-empty vector (p < 0.005). SOX3 protein nuclear expression was detected in 14% (4/27 cases) of ductal carcinoma cases, and pro-Caspase-3 expression was positive in 50% of the cases.Conclusion: Data suggest that SOX3 transcription factor upregulates apoptosis in breast cancer cell line MDA-MB-231, and has a down nuclear expression in ductal carcinoma cases, and need to be investigated as a tumor suppressor protein, and its loss of expression and non-nuclear action turn the cells resistant to apoptosis. Further studies are necessary to understand how SOX3 protein regulates the promoter regions of genes involved in apoptosis. [ABSTRACT FROM AUTHOR]

Lunasin is a soybean peptide with promising therapeutic applications in cancer and other diseases. It is described as an intrinsically disordered peptide, monomeric, and that can form an intramolecular disulfide bond between Cys10 and Cys22. In this study, we tested a new approach to obtain recombinant lunasin by Escherichia coli expression and performed its structural characterization. We expressed a lunasin sequence with an N-terminal 6× His-tag, B1 domain of Streptococcal protein G (GB1), and Tobacco etch virus (TEV) cleavage site (His6-GB1-lunasin), using pET-25b(+) vector. His6-GB1-lunasin purification using immobilized metal affinity chromatography achieved high recovery. We obtained a final yield of 12.0 (± 0.39) mg/L of recombinant lunasin with high purity. The molecular mass and conformation were as expected, as verified by liquid chromatography–mass spectrometry (LC–MS), electrospray ionization–ion mobility spectrometry–mass spectrometry (ESI–IMS–MS), electrospray ionization–mass spectrometry (ESI–MS), size-exclusion chromatography, circular dichroism, fluorescence spectroscopy, and one-dimensional 1H nuclear magnetic resonance. Additionally, the identity of lunasin and its complete amino acid sequence was confirmed by LC–MS/MS. Recombinant lunasin also showed antioxidant activity (2.92 ± 0.16 µmol of trolox equivalents/µmol lunasin) by oxygen radical absorbance capacity and inhibited cell migration of MDA-MB-231 cell line. On the other hand, for the first time, LC–MS, ESI–IMS–MS and ESI–MS analyses revealed, in addition to the reduced and oxidized monomeric forms, the presence of small populations of disulfide cross-linked dimeric species of lunasin. Overall, our data demonstrate the effectiveness of the GB1-tagging system to obtain lunasin, that lunasin can form disulfide cross-linked dimers, and that LC–MS, ESI–IMS–MS and ESI–MS are efficient analytical chemistry techniques to assess reduced and oxidized (monomer and dimer) species. [ABSTRACT FROM AUTHOR]

To understand whether previously synthesized novel hydrazone and oxadiazole derivatives have promising anticancer effects, docking studies and in vitro toxicity assays were performed on A-549, MDA-MB-231, and PC-3 cell lines. The antiproliferative properties of the compounds were investigated using molecular docking experiments. Each compound's best-docked poses, binding affinity, and receptor-ligand interaction were evaluated. Compounds' molecular weights, logPs, TPSAs, abilities to pass the blood-brain barrier, GI absorption qualities, and CYPP450 inhibition have been given. When the activities of these molecules were examined in vitro, for the A-549 cell line, hydrazone 1e had the minimum IC50 value of 13.39 μM. For the MDA-MB-231 cell line, oxadiazole 2l demonstrated the lowest IC50 value, with 22.73 μM. For PC-3, hydrazone 1d showed the lowest C50 value of 9.38 μM. The three most promising compounds were determined as compounds 1e, 1d, and 2a based on their minimum IC50 values, and an additional scratch assay was performed for A-549 and MDA-MB-231 cells, which have high migration capacity, for the three most potent molecules; it was determined that these molecules did not show a significant antimetastatic effect. [ABSTRACT FROM AUTHOR]

A new series of 4-aryl-2-(naphthalen-1-yl)thiazole (7a-b), 4-aryl/pyridyl-2-(2-substituted quinolin-4-yl)thiazole (13a-o) and 4-(pyridin-4-yl)-2-(quinolin-4-yl)thiazole (15) have been synthesized. The newly synthesized compounds were evaluated for anticancer activity against breast cell lines MDA-MB-231 and MCF-7. Among the derivatives compounds 7a, 7 b and 13e showed good activity against the MCF-7 cell line, compounds 13 m, 13o and 15 showed good activity against MDA-MB-231 cell line. The new analogs were also screened to evaluate their in vitro antimicrobial potential against Escherichia coli (NCIM 2574), Proteus mirabilis (NCIM 2388), Bacillus subtilis (NCIM 2063), Staphylococcus albus (NCIM 2178), Aspergillus niger (ATCC 504), and Candida albicans (NCIM 3100). Amongst the naphthalenyl-thiazole and quinolinyl-thiazole derivatives, ten compounds 7a, 7 b, 13a, 13 b, 13c, 13d, 13e, 13f, 13 h and 15 showed good activity against P. mirabilis. The structure-activity relationship study revealed that naphthalene, quinoline, and 2-phenyl quinoline tethered thiazole showed good activity against P. mirabilis. These compounds could assist in the development of lead compounds for the treatment of cancer and microbial infections. [ABSTRACT FROM AUTHOR]

Aim: Breast cancer is the most common frequently diagnosed malignancy among women and leading cause of cancer death in women worldwide. The aim of this study is 1) to increase the biocompatibility of the titanium dioxide (TiO2) nanoparticles (NPs) by coating it with PolyEthylene Glycol (PEG) and to develop a new nanostructure system and 2) to determine anticancer activity of doxorubicin (DOX) loaded PEG-TiO2 on MDA-MB-231 cell lines. Material and Methods: TiO2 nanoparticles used in this study were synthesized, coated with PEG, and PEG-TiO2 nanostructure system was loaded by DOX. UV analysis was performed on the prepared solutions. The synthesized drugs were applied to the MDA-MB-231 breast cancer cell line and cytotoxic effect of these drugs were determined by using MTT method. The MDA-MB-231 cells were treated with different concentrations of TiO2 (5-100 µg/ml) for 24, 48 and 72 hours. Apoptosis and necrosis were determined by fluorescence microscopy using the Hoechst 33258 (HO)/propidium iodide (PI) double staining. Results: The effects of TiO2, PEG-TiO2, DOX, and TiO2-PEG-DOX on the MDA-MB-231 cell line were compared with the control group and IC50 values were determined for 24, 48 and 72 hours. Conclusion: In this study, it was shown that the effect of TiO2-PEG-DOX nanostructured system on MDA-MB-231 cell line was inhibition growth in cancer cells and induction of apoptosis when compared with control group and DOX. [ABSTRACT FROM AUTHOR]

Abstract A phytochemical study on the stem bark of Metasequoia glyptostroboides led to the isolation of sixty-one diterpenoids and sesquiterpenoids, including seventeen previously undescribed compounds, metaglyptins A-Q. Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HRESIMS, and 1H, 13C and 2D NMR). The absolute configurations of metaglyptins I, J, and O were determined by the ECD data and single-crystal X-ray diffraction analysis. The undescribed compounds were evaluated for their cytotoxicity against HeLa, AGS, and MDA-MB-231 cancer cell lines. The results revealed that metaglyptin A exhibited moderate cytotoxicity against MDA-MB-231 cell line with IC 50 value of 20.02 μ M. Graphical abstract Seventeen previously undescribed diterpenoids and sesquiterpenoids, as well as forty-four known compounds, were isolated and structurally characterized from the stem bark of Metasequoia glyptostroboides. The isolated undescribed compounds were evaluated for their cytotoxic activity. Image 1 Highlights • Seventeen undescribed terpenoids were isolated from Metasequoia glyptostroboides. • Forty-four known diterpenoids and sesquiterpenoids were isolated. • Metaglyptin A exhibited moderate cytotoxicity against MDA-MB-231 cell line. [ABSTRACT FROM AUTHOR]

Introduction: This work studied on screening for cytotoxic activity in human breast cancer MDA-MB-231 cell line of extracts from different parts of this medicinal plant. Methods: MDA-MB-231 cells were cultured in DMEM supplemented with 10% FCS, 2 mM L-glutamine, 100 IU/mL penicillin and 100 µg/mL streptomycin. Cells were treated with extracts of F. indica at different concentrations (4 - 100 µg/mL) for 72 hours. Anti-proliferative effect was evaluated by MTT test; necrosis measured by LDH test; apoptosis activation determined by acridine orange/ethidium bromide staining, electrophoresis of DNA fragment, assays of DNA fragment and caspase 3 activity. Results: All extracts from root, stem and leaf of F. indica showed cytotoxic activity in human breast cancer MDA-MB-231 cell line as decreases in cell viability after treatment for 72h in the order: chloroform extracts > ethyl acetate extracts > aqueous extracts. For chloroform and ethyl acetate extracts of different parts, stem extracts exhibited the highest cytotoxic activity, after that root extracts > leaf extracts. The mechanism of cytotoxic activity of chloroform, ethyl acetate extracts form F. indica root and stem were necrosis by releasing of lactate dehydrogenase into culture medium and apoptosis activation of MDA-MB-231 cells measured as membrane bleeding, chromosome condensation as well as increases in DNA fragmentation and caspase 3 activity. Conclusion: All extracts of F. indica showed cytotoxic activity in human breast cancer MDA-MB-231 cell line by mechanism of necrosis and apoptosis activation. [ABSTRACT FROM AUTHOR]

Two platinum complexes [Pt(HL3)Cl]·H2O (3) and [Pt(HL4)Cl]·H2O (4) containing α- and β-naphthyl groups, respectively, were investigated in more detail in vitro and in vivo for antineoplastic activity. The cytotoxicity activity induced by these platinum(II) compounds against breast cancer (MDA-MB-231 and MCF-7), lung (A549), prostate (PC3), pancreas (BXPC-3), and normal peripheral blood mononuclear (PBMC) cells were evaluated by MTT assay. The cell viability MTT assay showed that complex (4) was more cytotoxic to all cancer cell lines tested and less cytotoxic against human PBMC. Therefore, complex (4) was selected to further investigate the mechanism of cytotoxic effects involved against MDA-MB-231 cell line (human triple-negative breast cancer). Sub-G1 analysis of the cell cycle showed that this complex induces cell death by apoptosis due to the cell loss of DNA content detected in flow cytometry. The cytotoxic effect induced by complex (4) was associated with the capability of the complex to induce mitochondrial membrane depolarization, as well as increase ROS levels and caspase activation, as a result of the activation of both extrinsic and intrinsic apoptosis pathways. Ultrastructural alterations were observed using scanning and transmission electron microscopy (SEM and TEM), such as membrane blebbing, filopodia reduction, empty mitochondrial matrix, and DNA fragmentation. Furthermore, complex (4) was tested in an MDA-MB-231 tumor nodule xenograft murine model and demonstrated a remarkable reduction in tumor size in BALB/c nude mice, when compared to the control animals. [ABSTRACT FROM AUTHOR]

Breast cancer is a highly heterogeneous disease that has been clinically divided into three main subtypes: estrogen receptor (ER)- and progesterone receptor (PR)-positive, human epidermal growth factor receptor 2 (HER 2)-positive, and triple-negative breast cancer (TNBC). With its high metastatic potential and resistance to endocrine therapy, HER 2-targeted therapy, and chemotherapy, TNBC represents an enormous clinical challenge. The genus Taraxacum is used to treat breast cancer in traditional medicine. Here, we applied aqueous extracts from two Taraxacum species, T. mongolicum and T. formosanum, to compare their potential antitumor effects against three human breast cancer cell lines: MDA-MB-231 (ER−, PR−, and HER2−), ZR-75-1 (ER+, PR+/−, and HER2−), and MCF-7 (ER+, PR+, and HER2−). Our results show that T. mongolicum exerted cytotoxic effects against MDA-MB-231 cells, including the induction of apoptosis, the reduction of cell proliferation, the disruption of the mitochondrial membrane potential, and/or the downregulation of the oxygen consumption rate. Both T. mongolicum and T. formosanum decreased cell migration and colony formation in the three cell-lines and exerted suppressive effects on MCF-7 cell proliferation based on metabolic activity and BrdU incorporation, but an enhanced proliferation of ZR-75-1 cells based on BrdU incorporation. T. formosanum induced ribotoxic stress in MDA-MB-231and ZR-75-1 cells; T. mongolicum did not. In summary, these findings suggest that T. mongolicum showed greater cytotoxicity against all three tested breast cancer cell lines, especially the TNBC MDA-MB-231 cell line. [ABSTRACT FROM AUTHOR]

Due to the role of cancer stem cells (CSCs) in tumor resistance and glycosphingolipid (GSL) involvement in tumor pathogenesis, we investigated the effect of a newly synthesized compound (3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide 1 on the percentage of CSCs and the expression of six GSLs on CSCs and non-CSCs on breast cancer cell lines (MDA-MB-231 and MCF-7). We also investigated the effect of 1 on the metabolic profile of these cell lines. The MTT assay was used for cytotoxicity determination. Apoptosis and expression of GSLs were assessed by flow cytometry. A GC–MS-coupled system was used for the separation and identification of metabolites. Compound 1 was cytotoxic for both cell lines, and the majority of cells died by treatment-induced apoptosis. The percentage of CSCs was significantly lower in the MDA-MB-231 cell line. Treatment with 1 caused a decrease of CSC IV6Neu5Ac-nLc4Cer+ MDA-MB-231 cells. In the MCF-7 cell line, the percentage of GalNAc-GM1b+ CSCs was increased, while the expression of Gg3Cer was decreased in both CSC and non-CSC. Twenty-one metabolites were identified by metabolic profiling. The major impact of the treatment was in glycolysis/gluconeogenesis, pyruvate and inositol metabolism. Compound 1 exhibited higher potency in MBA-MB-231 cells, and it deserves further examination. [ABSTRACT FROM AUTHOR]

Background and purpose: Histone deacetylation is one of the essential cellular pathways in the growth and spread of cancer, so the design of histone deacetylase (HDAC) inhibitors as anticancer agents is of great importance in pharmaceutical chemistry. Here, a series of indole acylhydrazone derivatives of 4-pyridone have been introduced as potential histone deacetylase inhibitors. Experimental approach: Seven indole-acylhydrazone-pyridinone derivatives were synthesized via simple, straightforward chemical procedures. The molecular docking studies were accomplished on HDAC2 compared to panobinostat. The cytotoxicity of all derivatives was studied on MCF-7 and MDA-MB-231 breast cancer cell lines by MTT assay. Findings / Results: Molecular docking studies supported excellent fitting to the HADC2 active site with binding energies in the range of -10 Kcal/mol for all derivatives. All compounds were tested for their cytotoxicity against MCF-7 and MDA-MB-231 cell lines; derivatives A, B, F, and G were the best candidates. The half-maximal inhibitory concentration (IC50) values on MCF-7 were below 25 mg/mL and much lower than those obtained on the MDA-MB-231 cell line. Conclusion and implications: The derivatives showed selectivity toward the MCF-7 cell line, probably due to the higher HDAC expression in the MCF-7 cell line. In this regard, debenzylated derivatives F and G showed slightly better cytotoxicity, which should be more studied in the future. Derivatives A, B, F, and G were promising for future enzymatic studies. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer is one of the most commonly diagnosed types of cancer worldwide. This cancer is treated with various methods like mastectomy, chemotherapy, hormone therapy, and radiotherapy. Among them, targeted therapy, like microRNA (miRNA) replacement therapy, is considered a new approach to treating breast cancer. Methods: Data analysis from TCGA datasets were used to investigate the expression of hsamiR- 146a-5p in breast cancer. MTT assay was used to evaluate the viability of MDA-MB-231 cells after hsa-miR-146a-5p ectopic expression. A wound-healing assay was used to observe migration in the MDA-MB-231 cell line and the effect of the hsa-miR-146a-5p ectopic expression on migration. Finally, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used as a method to determine the effect of the hsa-miR-146a-5p ectopic expression on the expression of CXCR4, β-catenin, MMP2, MMP9, and Vimentin genes known to be involved in invasion and migration of MDA-MB-231 cells. Results: Our results indicated that hsa-miR-146a-5p is not involved in apoptosis in the MDAMB- 231 cells, while it is highly effective in migration inhibition. MMP9, MMP2, CXCR4, and Vimentin expressions were suppressed by hsa-miR-146a-5p induction; however, it induced the expression of β-catenin. Conclusion: Some non-coding RNAs, such as hsa-miR-146a-5p, are effective in breast cancer targeted therapy. As cancer is a complicated disorder, therefore the combination of therapies might lead to novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Arctium minus (Hill) Bernh. (Asteraceae), which has a wide distribution area in Turkey, is a medicinally important plant. Eighty percent methanol extracts of the leaf, flower head, and root parts of A. minus were prepared and their sub-fractions were obtained. Spectrophotometric and chromatographic (high-performance liquid chromatography) techniques were used to assess the phytochemical composition. The extracts were evaluated for antioxidant activity by diphenyl-2-picrylhydrazil radical (DPPH●), 2,2′-Azino-bis 3-ethylbenzothiazoline-6-sulfonic acid (ABTS●+) radical scavenging, and β-carotene linoleic acid bleaching assays. Furthermore, the extracts were subjected to α-amylase, α-glucosidase, lipoxygenase, and tyrosinase enzyme inhibition tests. The cytotoxic effects of extracts were investigated on MCF-7 and MDA-MB-231 breast cancer cell lines. The richest extract in terms of phenolic compounds was identified as the ethyl acetate sub-fraction of the root extract (364.37 ± 7.18 mgGAE/gextact). Furthermore, chlorogenic acid (8.855 ± 0.175%) and rutin (8.359 ± 0.125%) were identified as the primary components in the leaves' ethyl acetate sub-fraction. According to all methods, it was observed that the extracts with the highest antioxidant activity were the flower and leaf ethyl acetate fractions. Additionally, ABTS radical scavenging activity of roots' ethyl acetate sub-fraction (2.51 ± 0.09 mmol/L Trolox) was observed to be as effective as that of flower and leaf ethyl acetate fractions at 0.5 mg/mL. In the β-carotene linoleic acid bleaching assay, leaves' methanol extract showed the highest antioxidant capacity (1422.47 ± 76.85) at 30 min. The enzyme activity data showed that α-glucosidase enzyme inhibition of leaf dichloromethane extract was moderately high, with an 87.12 ± 8.06% inhibition value. Lipoxygenase enzyme inhibition was weakly detected in all sub-fractions. Leaf methanol extract, leaf butanol, and root ethyl acetate sub-fractions showed 99% tyrosinase enzyme inhibition. Finally, it was discovered that dichloromethane extracts of leaves, roots, and flowers had high cytotoxic effects on the MDA-MB-231 cell line, with IC50 values of 21.39 ± 2.43, 13.41 ± 2.37, and 10.80 ± 1.26 µg/mL, respectively. The evaluation of the plant extracts in terms of several bioactivity tests revealed extremely positive outcomes. The data of this study, in which all parts of the plant were investigated in detail for the first time, offer promising results for future research. [ABSTRACT FROM AUTHOR]

[Display omitted] • The overexpression of sugar receptors in cancer cells can be used as a target for nanomedicines ; • Sucrose esters can be used to insert sugar moieties on the surface of nanovesicles without surface chemistry reactions; • 3D printed microfluidics has been used to efficiently manufacture sucrose decorated liposomes loaded with berberine; • Sucrose decorated liposomes showed increased uptake and antiproliferative effect on breast cancer cells compared to normal liposomes. Developing targeted drug delivery systems is an urgent need to decrease the side effects and increase the drug's efficiency. Most cancer cells show an increased sugar consumption compared to healthy cells due to the deregulation of sugar transporters. Consequently, liposomes, as a biocompatible nanocarrier, could be surface decorated by sugars to enhance drug targeting into cancer cells. Our work outlines a new strategy to easily manufacture sucrose decorated liposomes using sucrose stearate, a biocompatible and biodegradable non-ionic surfactant, with a scalable microfluidic approach. Sucrose decorated liposomes were loaded with berberine hydrochloride, a well-known phytochemical compound to investigate its effects on triple-negative breast cancer cells (MDA-MB-231). Using the microfluidic manufacturing system, we prepared berberine-loaded liposomes using a mixture of phosphatidylcholine and cholesterol with and without sucrose stearate with a size up to 140 nm and narrow polydispersity. Stability was confirmed for 90 days, and the in vitro release profile was evaluated. The formulations showed acceptable in vitro biocompatibility and significantly higher anti-proliferative effect on MDA-MB-231 cell line. These results have been confirmed by an increased uptake evaluated by flow cytometry and confocal microscopy. Taken together, our findings represent an innovative, easy, and scalable approach to obtain sugar decorated liposomal formulations without any surface-chemistry reactions. They can be potentially used as an anticancer targeted drug delivery system. [ABSTRACT FROM AUTHOR]

Breast cancer represents the most incident cancer in women. Surgery, chemotherapy, radiation therapy, and hormone therapy remain the main treatment for this type of cancer. However, increasing resistance to anti-cancer drugs through poor response for some types of breast cancer to treatments highlights the need to develop new therapeutic agents to fight the disease. In this study, we evaluated the anti-tumor potential of the Chartergellus-CP1 peptide isolated from the wasp venom of Chartergellus communis in human breast cancer cell lines MCF-7 (HR+) and MDA-MB-231 (triple-negative). Cells viability, morphology, cell cycle dynamics, reactive oxygen species (ROS) production, and apoptosis were assessed for both cell lines after exposure to Chartergellus-CP1 during 24 and 48 h. The results showed that Chartergellus-CP1 led to a significant increase of cells in the S phase in addition to a high generation of ROS (being more evident in the MCF-7 cell line) associated with apoptotic cell death. This work demonstrates, for the first time, the cytotoxic effects of Chatergellus-CP1 on human breast cancer cell lines including cell cycle profile, oxidative stress generation, and cell death mechanisms. [Display omitted] • Chartergellus-CP1 peptide from Chatergellus communis wasp venom was cytotoxic to MCF-7 and MDA-MB-231 breast cancer cells.. • Chartergellus-CP1 induced impairments on cell cycle dynamic, promotes ROS generation and causes apoptosis in both cell lines. • MCF-7 cell line was more sensitive to Chartergellus-CP1 peptide than the MDA-MB-231 cell line. [ABSTRACT FROM AUTHOR]

As a result of the serious issues connected to the bacterial infections, there is an imperious need to improve strong and ecofriendly antimicrobial polymers to overcome the limitations of conventional antimicrobial agents. In this trend, poloxamines (Tetronics) which are X‐shaped poly(ethylene oxide)–poly(propylene oxide) diblocks linked to a focal ethylenediamine group; were successfully modified to produce Tetronic Schiff base for enhancing the biological activities of Tetronic 1107. Modification of tetronic 1107 (T1107) was proceeded throughout chloroacetylation of T1107 followed by amination using p‐phenylenediamine then the latter was treated with different aldehydes to yield Tetronic Schiff bases. Characterization of Tetronic Schiff bases was carried out by 1H‐NMR, Fourier‐transform infrared spectroscopy, X‐ray diffraction, elemental analysis and thermogravimetric analysis (TGA) analyses. The antimicrobial activities of four tested compounds coded (EK1, EK2, EK3, and EK4) were quantified using Microtiter‐assay methods. The obtained data revealed potential antimicrobial activities for tested compounds against all tested microbes with priority against Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus. Sample coded EK4 exhibited the most effective treatment against P. aeruginosa, Candida albicans, S. aureus and E. Coli with minimal inhibitory concentration values of 6, 16, 12.5, and 1.5 μM, respectively. Furthermore, the safety results confirmed that EK4 and EK1 were the safest treatment with IC50 values of 76.01 and 62.67 μM, respectively. In addition, all tested compounds showed significant anticancer effects against MDA‐MB‐231cell line, while EK3 was effective treatment against A549 cell line with IC50 values of 39.63 μM. Meanwhile, both EK2 and EK4 showed the highest selectivity index (SI) values against MDA‐MB‐231 cell line with values 2.5 and 3.07, respectively. Interestingly, EK4 showed the maximum SI values on A549 and Hep‐G2 cell lines with values 1.62 and 1.52, respectively. [ABSTRACT FROM AUTHOR]

Poly ε-caprolactone (PCL) synthesized by ring-opening polymerization method, and then it blended with polylactic acid (PLA). The blend was loaded with Cucurbita moschata leaf extract. The prepared PCL/PLA blend loaded with C. moschata was characterized with ATR-IR, TGA, and DSC; also the surface morphology was examined with an optical microscope. The thermal analysis results showed that the plant extract reduces the thermal stability and melting temperatures of the pure polymer blends. Optical microscope images showed that the plant extract filled the spaces between the polymer molecules. The antimicrobial effects of the pure polymer blend, pure plant leaf extract, and plant-loaded polymer blend against Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Bacillus megaterium, and Candida albicans microorganisms were examined, and it was observed that the antimicrobial effects increase with increasing concentration. Finally, the cytotoxic activities of the samples on the human breast cancer (MDA-MB-231) cell line were performed by the MTT analysis method. While the C. moschata leaf extract and polymer blend showed cytotoxic effect, the cytotoxic effect of the polymer blend loaded with plant extract was quite low. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is becoming a tumor with the highest morbidity rate, and inflammation-induced cell death namely pyroptosis reportedly plays dual roles in cancers. However, the specific mechanism between pyroptosis and the clinical prognosis of breast cancer patients is indistinct. Hence, novel pyroptosis-related biomarkers and their contributing factors deserve further exploration to predict the prognosis in breast cancer. Methods: Pearson's correlation analysis, and univariate and multivariate Cox regression analysis were utilized to obtain six optimal pyroptosis-related gene prognostic signatures (Pyro-GPS). The risk score of each breast cancer patient was calculated. Next, a Pyro-GPS risk model was constructed and verified in TCGA cohort (n=1,089) and GSE20711 cohort (n=88). Then analyses of immune microenvironment, genomic variation, functional enrichment, drug response and clinicopathologic feature stratification associated with the risk score of Pyro-GPS were performed. Subsequently, a nomogram based on the risk score and several significant clinicopathologic features was established. Ultimately, we further investigated the role of CCL5 in the biological behavior of MDA-MB-231 cell line. Results: The low-risk breast cancer patients have better survival outcomes than the high-risk patients. The low-risk patients also show higher immune cell infiltration levels and immune-oncology target expression levels. There is no significant difference in genetic variation between the two risk groups, but the frequency of gene mutations varies. Functional enrichment analysis shows that the low-risk patients are prominently correlated with immune-related pathways, whereas the high-risk patients are enriched in cell cycle, ubiquitination, mismatch repair, homologous recombination and biosynthesis-related pathways. Pyro-GPS is positively correlated with the IC50 of anti-tumor drugs. Furthermore, comprehensive analyses based on risk score and clinicopathological features were performed to predict the prognosis of breast cancer patients. Additionally, in vitro experiments confirmed that breast cancer cells with high expression of CCL5 had weaker proliferation, invasion and metastasis abilities as well as stronger apoptosis and cell cycle arrest abilities. Conclusions: The risk score of Pyro-GPS can serve as a promising hallmark to predict the prognosis of BRCA patients. Risk score evaluation may assist to acquire relevant information of tumor immune microenvironment, genomic mutation status, functional pathways and drug sensitivity, and thus provide more effective personalized strategies. [ABSTRACT FROM AUTHOR]

Tumor cells exhibit altered cholesterol content. However, cholesterol structural subcellular distribution and implication in cancer cell invasion are poorly understood mainly due to difficulties to investigate cholesterol both quantitatively and qualitatively and to compare isogenic cell models. Here, using the MCF10A cell line series (non-tumorigenic MCF10A, pre-malignant MCF10AT and malignant MCF10CAIa cells) as a model of breast cancer progression and the highly invasive MDA-MB-231 cell line which exhibits the common TP53 mutation, we investigated if cholesterol contributes to cancer cell invasion, whether the effects are specific to cancer cells and the underlying mechanism. We found that partial membrane cholesterol depletion specifically and reversibly decreased invasion of the malignant cell lines. Those cells exhibited dorsal surface cholesterol-enriched submicrometric domains and narrow ER-plasma membrane and ER-intracellular organelles contact sites. Dorsal cholesterol-enriched domains can be endocytosed and reach the cell ventral face where they were involved in invadopodia formation and extracellular matrix degradation. In contrast, non-malignant cells showed low cell invasion, low surface cholesterol exposure and cholesterol-dependent focal adhesions. The differential cholesterol distribution and role in breast cancer cell invasion provide new clues for the understanding of the molecular events underlying cellular mechanisms in breast cancer. [ABSTRACT FROM AUTHOR]

Cancer is one of the most lethal diseases in the world, and the development and improvement of treatments used in cancer therapies are extremely important for a better quality of life for patients. In view of the current problems in drug administration such as low solubility and adverse effects, the activity of a solid lipid nanoparticle containing docetaxel (SLN-DTX), a drug already used in conventional therapies, was evaluated in a cell line (MDA-MB-231) of one of the most aggressive types of breast cancer with the worst prognosis, triple-negative breast cancer. Viability tests indicated that SLN-DTX has a greater dependence on the treatment dose when compared to the free drug, which indicates a more controlled release of the drug, and both reduced viability by around 50% at a concentration of 1 µg/mL after 72 h. Transmission electron microscopy (TEM) and confocal and light microscopy analyses indicated that after treatment the cells enter a mitotic catastrophe, characteristic of antimitotic drugs that usually make cells progress to death or senescence. Cells treated with both DTX and SLN-DTX showed significant inhibition of mobility, 73.6% and 66.5% when treated with SLN-DTX and DTX, respectively, compared to the 11.4% of the control after 72 h, characteristics that are very relevant in tumor development and progression. SLN-DTX demonstrated its great potential as a nanocarrier by maintaining and improving the drug's action in the MDA-MB-231 cell line. [ABSTRACT FROM AUTHOR]

• Four mononuclear and dinuclear carboxamide Pd complexes isolated. • Molecular structures confirmed using single crystal X-ray analyses. • Interactions of the Pd complexes with CT-DNA) investigated. • BSA interactions studies established static quenching mechanism. • Cytotoxic effects of the complexes examined in three cancer cell lines. Reactions of ligands [ N 2, N 3-bis(pyridin-2-yl)pyrazine-2,3-dicarboxamide] (L1), [ N 2, N 3-bis(6-methylpyridin-2-yl)pyrazine-2,3-dicarboxamide] (L2), [ N 2, N 3-bis(4-methylpyridin-2-yl)pyrazine-2,3-dicarboxamide] (L3) and [ N 2, N 3-bis(quinoline-8-yl)pyrazine-2,3-dicarboxamide] (L4) with [PdCl 2 (NCMe) 2 ] afforded the respective palladium(II) complexes: [Pd 2 (L1) 2 Cl 2 ] (Pd1) , [Pd 2 (L2) 2 Cl 2 ] (Pd2) , [Pd 2 (L3) 2 Cl 2 ] (Pd3) and [Pd(L4) Cl] (Pd4). Molecular structures of complexes Pd1 and Pd3 are dinuclear containing two bridging bidentate ligand units. The interactions of the palladium complexes (Pd1 - Pd4) with calf thymus DNA (CT-DNA) were monitored using UV–Vis and fluorescence spectroscopy and revealed intercalative binding modes, with intrinsic binding constants (K b) in the order of 106 M−1. Bovine serum albumin (BSA) interaction was evaluated using fluorescence techniques and displayed a static quenching mechanism. The cytotoxic effects of the complexes Pd1-Pd4 were examined against human breast cancer cell lines MCF-7 and MDA-MB-231, and human transformed lung cell line MRC5-SV2 (a model of lung cancer) and its parental normal lung fibroblast cell line MRC5. While the complexes Pd1 and Pd4 showed significant to moderate cytotoxicity against MCF-7 (IC 50 of 11.2 µM and 61.5 µM, respectively), complexes Pd2 and Pd3 were inactive. All the complexes were inactive against the MDA-MB-231 cell line, and Pd2-Pd4 were inactive against the MRC5-SV2 cell line. Compounds Pd1 exhibited lower cytotoxicity against the normal cell line MRC5. [Display omitted] [ABSTRACT FROM AUTHOR]

Phosphonate analogues of α-amino acids are increasingly valued for their significant potential in medicinal chemistry. Fluorine is a "magic" element that plays a huge role in modulating the properties of organic compounds. In this work, we combined the two pharmacophores in the synthesis of three series of new α-aminophosphonates. These compounds were obtained by diastereoselective hydrophosphonylation of imines prepared by an environmentally friendly mechanochemical approach. Results of computational SwissADME analysis suggested favorable drug-like properties of the α-aminophosphonates and indicated their potential for interaction with diverse biological targets including proteases, showing promising pharmacokinetic profiles compared to 5-fluoro-2′-deoxyuridine (FdU) used as a standard anticancer drug. Screening against ten cancer cell lines from seven types of cancer showed that five of the twenty compounds tested (1c , 2a , 2h , 3e , and 3f) exhibited superior activity against the HeLa cell line and lower cytotoxicity against normal MRC-5 cells than FdU. Compound 3e showed notable inhibitory effect on the MDA-MB-231 cell line, while 3a , 3h , and 3g demonstrated significant cytotoxic activity against U-87 MG and U-251 MG lines. Molecular docking highlighted the strong binding of compound 2a to the urokinase-type plasminogen activator (uPA) protein, with a binding affinity of −6.41 kcal/mol, suggesting the anti-metastatic potential of the compound. These findings enable to position the newly synthesized α-aminophosphonates as promising scaffolds for developing targeted anticancer therapies for metastatic cancers characterized by elevated uPA expression. [Display omitted] • New class of fluorinated α-aminophosphonates was synthesized diastereoselectively. • The cytotoxicity of these compounds was tested against seven types of cancer. • The mean values of IC 50 ranged from 8.71 μM for HeLa to 89.54 μM for MDA-MB-231. • Compound 2a strongly binds to the structure of urokinase-type plasminogen activator protein. • The synthesized compounds provide scaffold for development of new anticancer drugs. [ABSTRACT FROM AUTHOR]

• A new set of quinolin-4-ylcarbonylhydrazine derivatives having 2-arylamido-3-arylacryloyl moiety has been synthesized. • The newly synthesized derivatives were evaluated for their cytotoxic activity against MDA-MB-231 cancer cells. • Flow cytometric measurements were carried out for the most potent molecule. • Active compound was tested for β-tubulin assembly inhibition. • Mitochondrial membrane potential was assessed for the most active compound. A new set of quinolin-4-ylcarbonylhydrazine derivatives 7a-i and 9a,b bearing 3-arylacryloyl moiety has been synthesized and investigated for their potential anticancer activity. The synthetic protocol involves the following step: the target quinoline derivatives 7a-i and 9a,b appended to the acryloyl moiety were synthesized from quinolin-4-carbohydrazide intermediate with respective ethyl 2-arylamido-3-arylacrylate compounds. The cytotoxic activity study was evaluated using the functional MTT method. The most of target compounds displayed potent cytotoxic activity against MDA-MB-231 cell line. Among them, compounds 7d and 7 h were found to be promising antiproliferative agents with IC 50 values of 4.04 and 1.78 μM, respectively, relative to the effective anticancer drug, Dox (IC 50 = 5.33 μM). Compound 7 h exhibited cytotoxic activity by causing cell cycle to block at G2/M phase in addition to pro-apoptotic effect, as shown by flow cytometric measurement. In addition, the inhibitory action against β-tubulin polymerization was investigated. Finally, compound 7 h diminished the level of mitochondrial potential by almost 2.8-fold compared to control, indicating that the cellular death proceeds through the provoke of the intrinsic mitochondrial pathway of apoptosis. [ABSTRACT FROM AUTHOR]

• Synthesis, structural studies & application of Schiff base 1 and its Zn(II)-complex 2. • Complex 2 shows better effect in vitro cytotoxicity as compared to 1 Against MDA-MB-231 cell line. • Chromone-appended 1 acts as an exceptionally selective colorimetric receptor for Cu2+. • Complex 2 serves as ultrasensitive fluorescent probe for Ag+ and Fe3+ distinctly. • Interaction with Ag+ forms [2·Ag(NO3)]n and Fe3+ forms [2·{Fe(NO3)2H2O)}2] complex. • Comprehensive DFT studies have been carried out to validate the mechanism and binding. Present article delineates the design and synthesis of a chromone-appended Schiff base (1) and its complexes with Zn(II) (2) and Cu(II) (3), which have been characterized by various spectro-analytical techniques i.e., elemental analysis, FTIR, 1H & 13C NMR, ESI-MS, UV−vis and fluorescence. Structures of 1 and 3 have also been elucidated using single crystal X-ray diffraction analysis. Compounds 2 showed significant effect in vitro cytotoxicity as compared to 1 Against MDA−MB-231 cell line. Interestingly, 1 serves as a chromogenic sensor for Cu2+ with exceptional selectivity whereas, 2 serves as an ultrasensitive fluorescent probe for Ag+ and Fe3+ in mixed aqueous−ethanol. The presence of Ag+ causes ratiometric change in the fluorescence spectral feature of 2 whereas Fe3+ induces ' turn-off ' fluorescence in 2. Probe−analyte binding stoichiometry suggested by Job's plot analysis, ESI−MS and DFT studies, has been found to be 1:1 for 1 with Cu2+ and 2 with Ag+ whereas, 1:2 between 2 and Fe3+. Based on diverse analyses and binding constants, it is observed that 2 offers higher selectivity toward Ag+ over Fe3+. Limit of detection (LoD) of 1 for Cu2+ and 2 for Ag+ and Fe3+ have been found to be 2.33 nM, 22.4 µ M and 2.05 µ M, respectively. Complexes 2 +Ag+ and 2 +Fe3+ characterized by ESI−MS whereas DFT studies have been carried out to investigate the deeper bonding insights and provide support in our experimental investigations. Further, detection of Ag+ and Fe3+ has been practically accomplished in real water samples using probe 2. [Display omitted] Present research entails synthesis, characterization and structural validation along with anticancer activities, UV−vis and fluorescent detection studies of chromone−based probes 1 and 2 toward colorimetric recognition of Cu2+ and ultrafast fluorescent detection of Ag+ and Fe3+ with excellent reusability and LoDs. Both 1 and 2 exhibits anti-cancer properties Against MDA−MB-231 cell line. Detailed DFT studies to support the experimental results and practical application in real water samples have also been accomplished. [ABSTRACT FROM AUTHOR]

The complex structure of glycosphingolipids (GSLs) supports their important role in cell function as modulators of growth factor receptors and glutamine transporters in plasma membranes. The aberrant composition of clustered GSLs within signaling platforms, so-called lipid rafts, inevitably leads to tumorigenesis due to disturbed growth factor signal transduction and excessive uptake of glutamine and other molecules needed for increased energy and structural molecule cell supply. GSLs are also involved in plasma membrane processes such as cell adhesion, and their transition converts cells from epithelial to mesenchymal with features required for cell migration and metastasis. Glutamine activates the mechanistic target of rapamycin complex 1 (mTORC1), resulting in nucleotide synthesis and proliferation. In addition, glutamine contributes to the cancer stem cell GD2 ganglioside-positive phenotype in the triple-negative breast cancer cell line MDA-MB-231. Thieno[2,3-b]pyridine derivative possesses higher cytotoxicity against MDA-MB-231 than against MCF-7 cells and induces a shift to aerobic metabolism and a decrease in S(6)nLc4Cer GSL-positive cancer stem cells in the MDA-MB-231 cell line. In this review, we discuss findings in MDA-MB-231, MCF-7, and other breast cancer cell lines concerning their differences in growth factor receptors and recent knowledge of the main biochemical pathways delivering distinct glycosphingolipid patterns during tumorigenesis and therapy.

Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks an actionable target with limited treatment options beyond conventional chemotherapy. Therapeutic failure is often encountered due to inherent or acquired resistance to chemotherapy. Previous studies implicated PI3K/Akt/mTOR signaling pathway in cancer stem cells (CSCs) enrichment and hence chemoresistance. The present study aimed at investigating the potential effect of piperine (PIP), an amide alkaloid isolated from Piper nigrum, on enhancing the sensitivity of TNBC cells to doxorubicin (DOX) in vitro on MDA-MB-231 cell line and in vivo in an animal model of Ehrlich ascites carcinoma solid tumor. Results showed a synergistic interaction between DOX and PIP on MDA-MB-231 cells. In addition, the combination elicited enhanced suppression of PI3K/Akt/mTOR signaling that paralleled an upregulation in this pathway’s negative regulator, PTEN, along with a curtailment in the levels of the CSCs surrogate marker, aldehyde dehydrogenase-1 (ALDH-1). Meanwhile, in vivo investigations demonstrated the potential of the combination regimen to enhance necrosis while downregulating PTEN and curbing PI3K levels as well as p-Akt, mTOR, and ALDH-1 immunoreactivities. Notably, the combination failed to change cleaved poly-ADP ribose polymerase levels suggesting a pro-necrotic rather than pro-apoptotic mechanism. Overall, these findings suggest a potential role of PIP in decreasing the resistance to DOX in vitro and in vivo, likely by interfering with the PI3K/Akt/mTOR pathway and CSCs.

Annona muricata L., known as graviola, is an evergreen plant of the tropical regions and is a rich source of natural products. Graviola has various biological activities, and it is best known for its anticancer activity. This study aimed to investigate the effects of crude graviola extract in vitro on breast cancer cells; in particular, we aimed to identify an agent against triple negative breast cancer (TNBC). We used the TNBC MDA-MB-231 cell line as the experimental model and the ER(+) non-TNBC MCF-7 breast cancer cell line as the control. We identified annonaceous acetogenins, including annonacin isomers, characteristic to this plant by using liquid chromatography tandem mass spectrometry (LC/MS/MS). We observed a significant decrease in the cell viability in both cell lines within 48 h, whereas impaired cell motility and invasiveness were observed only in the MDA-MB-231 cell line. While the MCF-7 cells showed an ER-dependent mechanism of apoptosis, the apoptosis of MDA-MB-231 cells was governed by an intrinsic apoptotic pathway triggered by graviola leaf extract (GLE). [ABSTRACT FROM AUTHOR]

This study aimed to investigate metabolic changes following the acquisition of resistance to doxorubicin in the triple-negative breast cancer (TNBC) cell line MDA-MB-231. Two drug-resistant cell lines, DOX-RES-50 and DOX-RES-100, were generated by treating MDA-MB-231 cells with doxorubicin for 24 h and allowing them to recover for six weeks. Both drug-resistant cell lines demonstrated an increase in doxorubicin IC50 values, indicating acquired drug resistance. Metabolomics analysis showed clear separation between the parental MDA-MB-231 cell line and the drug-resistant cell lines. Pathway analysis revealed that arginine and proline metabolism, glutathione metabolism, and beta-alanine metabolism were significantly perturbed in the drug-resistant cell lines compared to the parental cell line. After matching signals to an in-house library of reference standards, significant decreases in short- and medium-chain acylcarnitines and significant increases in long-chain acylcarnitines, 5-oxoproline, and 7-ketodeoxycholic acid were observed in the resistant cell lines as compared to the parental MDA-MB-231 cell line. In addition to baseline metabolic differences, we also investigated differences in metabolic responses in resistant cell lines upon a second exposure at multiple concentrations. Results indicate that whereas the parental MDA-MB-231 cell line had many metabolites that responded to doxorubicin in a dose-dependent manner, the two resistant cell lines lost a dose-dependent response for the majority of these metabolites. The study’s findings provide insight into how metabolism is altered during the acquisition of resistance in TNBC cells and how the metabolic response to doxorubicin changes upon repeated treatment. This information can potentially identify novel targets to prevent or reverse multi-drug resistance in TNBC, and also demonstrate the usefulness of metabolomics technology in identifying new mechanisms of drug resistance in cancer and potential drug targets.

Chemical investigation of the Tinospora sinensis led to the isolation of a new cadinane sesquiterpene (1) and twelve known sesquiterpenes (2 − 13). The structures of these compounds were deduced using a suite of comprehensive spectroscopic techniques including NMR, MS etc. , and the absolute configuration of 1 was established through a combination of TDDFT calculations and chemical methods. Compound 1 demonstrated mild cytotoxicity against MDA-MB-231 cell line, with an inhibition rate of 46.8% and 54.2% at 50 μmol/L and 100 μmol/L, respectively. Compounds 1 , 5 − 13 were reported to exist in the Menispermaceae family for the first time. Furthermore, the chemotaxonomic significance of the isolates is also discussed. • Thirteen sesquiterpenes were isolated from the Tinospora sinensis. • A new cadinane sesquiterpene was isolated from the Tinospora sinensis. • Compounds 1 , 5–13 were isolated from Menispermaceae for the first time. • The chemotaxonomic significance of the isolates is discussed. [ABSTRACT FROM AUTHOR]

An important contributing factor to the growth of aggressive and treatment-resistant tumors is tumor hypoxia. In this investigation, we created a unique tracer, 64Cu-biacetyl-bis(4-methyl-3-semicarbazone) Complex (64Cu-[APSC] 2), for hypoxia imaging. Numerous spectral and electrochemical analyses were used to characterize the synthesized ligand and its metal complex. The coordination of the metal in the metal complex was also supported by DFT (B3LYP model) calculations. The radiochemical yields and purities of 64Cu-[APSC] 2 were found to be quantitative, as determined by TLC and HPLC analyses. Stability studies in human plasma demonstrated that 64Cu-[APSC] 2 remained steady for at least four hours while being incubated at 37 °C. MDA-MB-231 cell-line xenografts were placed in nude mice for biodistribution research. The results revealed significant accumulation of the tracer in tumors after 2 h post-injection, which correlated with the redox potential and reactive oxygen species. These findings suggest that 64Cu-[APSC] 2 shows promising evidence as a theranostic radiopharmaceutical for hypoxic tumors. [ABSTRACT FROM AUTHOR]

Metastatic cancer remains a formidable challenge in anticancer therapy. Despite efforts to develop effective antimetastasis drugs over the past half-century, currently approved treatments fall short of expectations. This report highlights the promising antiproliferative activity of a ruthenium-based therapeutic agent, namely dichlorido(p -cymene)[2-amino-4-(pyridin-3-yl)-4 H -benzo[ h ]-chromene-3-carbonitrile]ruthenium(II) (complex 1) against metastatic cell lines. Complex 1 shows significant efficacy in metastatic LoVo and Du-145 cell lines at nanomolar concentrations, being markedly more active than clinically used anticancer cisplatin. Studies on the MDA-MB-231 cell line, which displays invasive characteristics, demonstrated that 1 significantly reduces cell invasion. This efficacy was confirmed by its impact on matrix metalloproteinase production in MDA-MB-231 cells. Given that cell migration drives cancer invasion and metastasis, complex 1 's effect on MDA-MB-231 cell migration was evaluated via wound healing assay and vimentin network analysis. Results indicated a strong reduction in migration. A re-adhesion assay further demonstrated that 1 significantly lowers the re-adhesion ability of MDA-MB-231 cells compared to cisplatin. To better simulate the human body environment, a 3D spheroid invasion assay was used. This method showed that 1 effectively inhibits tumor spheroids from infiltrating the surrounding extracellular matrix. This study underscores the potential of (arene)ruthenium(II) complexes with naphthopyran ligands as potent antimetastatic agents for chemotherapy. • (Arene)Ru(II) complex with naphthopyran (1) exhibits antimetastatic efficacy. • 1 reduces invasion and migration activity of tumor cells displaying invasive traits. • 1 prevents metastatic 3D spheroids from infiltrating the adjacent extracellular matrix. • (Arene)Ru(II) complexes with naphthopyran represent promising antimetastatic agents for chemotherapy. [ABSTRACT FROM AUTHOR]

Chemotherapeutics such as platinum-based drugs are commonly used to treat several cancer types, but unfortunately, their use is limited by several side effects, such as high degradation of the drug before entering the cells, off-target organ toxicity and development of drug resistance. An interesting strategy to overcome such limitations is the development of nanocarriers that could enhance cellular accumulation in target cells in addition to decreasing associated drug toxicity in normal cells. Here, we aim to prepare and characterize a graphene-oxide-based 2D nanoplatform functionalised using highly branched, eight-arm polyethylene-glycol, which, owing to its high number of available functional groups, offers considerable loading capacity over its linear modalities and represents a highly potent nanodelivery platform as a versatile system in cancer therapy. The obtained results show that the GO@PEG carrier allows for the use of lower amounts of Pt drug compared to a Pt-free complex while achieving similar effects. The nanoplatform accomplishes very good cellular proliferation inhibition in osteosarcoma, which is strictly related to increased cellular uptake. This enhanced cellular internalization is also observed in glioblastoma, although it is less pronounced due to differences in metabolism compared to osteosarcoma. The proposed GO@PEG nanoplatform is also promising for the inhibition of migration, especially in highly invasive breast carcinoma (i.e., MDA-MB-231 cell line), neutralizing the metastatic process. The GO@PEG nanoplatform thus represents an interesting tool in cancer treatment that can be specifically tailored to target different cancers. [ABSTRACT FROM AUTHOR]

Breast cancers exhibit different response to drug treatment. In this work, we analyze and compare the effect of two anticancer drugs differing in their primary action, miltefosine and cisplatin (cis-Pt), on two different breast cancer (the low—(MCF-7) and high—(MDA-MB-231) metastatic) cell lines, and one normal epithelial (MCF-10A) breast cell lines. The effect of cip-Pt and miltefosine on the thermodynamic behavior of the cancer cell lines was analyzed by differential scanning calorimetry, the cell morphology and viability were determined by optical microscopy and MTT test. We revealed distinct effects of miltefosine and cis-Pt on the thermodynamic behavior and viability of the cancer and normal cells. Importantly, the normal MCF-10A cells were drastically affected by miltefosine, while not by cis-Pt. MDA-MB-231 cell line, on the other hand, is more susceptible to cis-Pt than MCF-7 cells, while both cancer cell lines are equally affected by miltefosine. The drug-associated alteration of the thermal unfolding of the cells constituents correlated with the changes in the cell viability. The altered thermodynamic behavior of the cancer cells upon the drug treatment strongly indicates altered conformations of the proteins in cancer cell membrane and cellular matrix, and the DNA-containing structures. [ABSTRACT FROM AUTHOR]

Background: The assembly and disassembly of the focal adhesions (FA) components occurs throughout life cycle of adhesion, with conservation of balance between removal and recruitment rate during temporal stages. Previous studies have demonstrated that phosphotidyilinositols play a role in regulating FA turnover. However, a little attention has been given to quantify the dynamics changes of Phosphatidylinositol 3,4,5- trisphosphate (PtdIns (3,4,5) P3) within and during fast and slow turnover rates of FA. Methods: MDA-MB-231 breast cancer cell line was used as a model in this study due to high metastatic and motile. These cells were co-transfected with GFP- paxillin/vinculin, as FA marker, and the GFP/mCherry-Btk-PH, as a biosensor to visualize PtdIns (3,4,5) P3. Confocal time-lapse images were used to monitor changes or differences in the local generation of PtdIns (3,4,5) P3 within and during assembly and disassembly of FA. Following transfection, immunostaining was used to examine the spatial colocalization between FA and PtdIns (3,4,5) P3. Results: Our data demonstrated that PtdIns (3,4,5) P3 co-localized with FAs and increase during assembly and decline during disassembly of FA which exhibits slow turnover rates and was in a constant level during assembly and disassembly of FA that displays fast turnover rates. Conclusions: Our result suggested that the dynamic changes of PtdIns (3,4,5) P3, it may depend on components undergo turnover, such that early, nascent FA displays fast turnover rates and mature FA exhibits slow turnover rates. Thus, the local enrichment of PtdIns (3,4,5) P3 enhances FA assembly and disassembly activation. [ABSTRACT FROM AUTHOR]

Nisin is an antibacterial peptide with anticancer properties, but the main drawback is its rapid enzymatic degradation and limited permeation across the cell membrane. This research aims to overcome these drawbacks by developing nisin-loaded nanoparticles (NPN) with improved cytotoxic effects. PLGA nanoparticles are one of the most effective biodegradable and biocompatible drug delivery carriers. In the present study, nisin-loaded nanoparticles showed enhanced anticancer effects. NPN was prepared by a double emulsion solvent evaporation method and characterized for different parameters. The cytotoxic investigation of NPN was carried out on various cell lines, including A549, SW-620, HT-29, PC-3, MDA-MB-231, MCF-7, MiaPaca-2, and fR2 by sulforhodamine B (SRB) assay. Mechanistic investigation of cellular cytotoxicity was performed by using bright-field microscopy, DAPI staining, intracellular reactive oxygen species (ROS), changes in mitochondrial membrane potential (ΔΨm), Western blotting and cellular uptake study. A comparative cytotoxicity study of nisin and NPN was performed on normal breast epithelial cells (fR2). NPN showed spherical shape, 289.09 ± 3.63 nm particle size, and 63.37 ± 3.12% entrapment efficiency. NPN was more cytotoxic to the MDA-MB-231 cell line, showing higher nuclear fragmentation, ROS generation, depletion of ΔΨm, and enhanced intracellular uptake with apoptosis signs compared with nisin and with no cytotoxicity on normal cells. The findings suggest that nisin delivery via PLGA nanoparticles can be used to treat cancer without significant effects on healthy cells. [ABSTRACT FROM AUTHOR]

Background: CCR5 is a motility chemokine receptor implicated in tumor progression, whose activation and subsequent endocytosis may identify highly aggressive breast cancer cell subtypes likely to spread into the circulatory system.Methods: The MDA-MB-231 cell line was used to model and visualize CCR5 activation by stimulation with RANTES, in an effort to quantify CCR5 endocytosis from the cell surface to the perinuclear space. CCR5 expression was then examined in tumor-associated cells (TACs), consisting of circulating tumor cells and circulating stromal cells, isolated from the peripheral blood of 54 metastatic breast cancer (mBC) patients to evaluate these CCR5 pooling patterns as they relate to progression and survival over 2 years.Results: In MB231 experiments, it was observed that CCR5 formed ~ 1 micron clusters identified as "CCR5 pools" on the surface of the cell, which in the presence of RANTES were endocytosed and translocated to the cell cytoplasm. When TACs from patients were analyzed, CCR5 pools were observed on the cell surface and translocating to the nuclear area, with CCR5 also having a positive statistical correlation between increased numbers of TACs and increased CCR5 pools on the cells. Further, it was determined that patients with very high numbers of CCR5 (> 10 CCR5 pools), specifically in the circulating stromal cells, were associated with worse progression-free survival (hazard ratio = 4.5, p = 0.002) and worse overall survival (hazard ratio = 3.7, p = 0.014).Conclusions: Using a liquid biopsy approach, we evaluated two populations of tumor-associated cells emanating from primary tumors, with data suggesting that upregulation of the motility chemokine CCR5 in TACs provides clinically relevant opportunities for treating and tracking drug targetable receptors in mBC. [ABSTRACT FROM AUTHOR]

Natural compounds are proper tools for inhibiting cancer cell proliferation. Hence, the search for these ligands of overexpressed receptors in breast cancer has been a competitive challenge recently and opens new avenues for drug discovery. In this research, we have investigated molecular interactions between natural products and overexpressed receptors in breast cancer using molecular docking and dynamic simulation approaches followed by extraction of the best ligand from Citrus limetta and developing for nanoscale encapsulation composed of soy lecithin using a sonicator machine. The encapsulation process was confirmed by DLS and TEM analyses. Anticancer activity was also examined using MTT method. Among the investigated natural compounds, hesperidin was found to bind to specific targets with stronger binding energy. The molecular dynamics results indicated that the hesperidin-MCL-1 complex is very stable at 310.15 K for 200 ns. The RP-HPLC analysis revealed that the purity of extracted hesperidin was 98.8% with a yield of 1.72%. The results of DLS and TEM showed a strong interaction between hesperidin and lecithin with an entrapped efficiency of 92.02 ± 1.08%. Finally, the cytotoxicity effect of hesperidin was increased against the MDA-MB-231 cell line with an IC50 value of 62.93 μg/mL after encapsulation, whereas no significant effect against the MCF10A cell line. We showed for the first time that hesperidin is a flexible and strong ligand for the MCL-1 receptor. Also, it has the in vitro ability to kill the MDA-MB-231 cell lines without having a significant effect on the MCF10A cell lines. Therefore, hesperidin could be used as a food ingredient to generate functional foods. [ABSTRACT FROM AUTHOR]

A new type of hybrid polymer particles capable of carrying the cytostatic drug doxorubicin and labeled with a gallium compound was prepared. These microparticles consist of a core and a hydrogel shell, which serves as the structural matrix. The shell can be employed to immobilize gallium oxide hydroxide (GaOOH) nanoparticles and the drug, resulting in hybrid beads with sizes of approximately 3.81 ± 0.09 μm. The microparticles exhibit the ability to incorporate a remarkably large amount of doxorubicin, approximately 0.96 mg per 1 mg of the polymeric carrier. Additionally, GaOOH nanoparticles can be deposited within the hydrogel layer at an amount of 0.64 mg per 1 mg of the carrier. These nanoparticles, resembling rice grains with an average size of 593 nm by 155 nm, are located on the surface of the polymer carrier. In vitro studies on breast and colon cancer cell lines revealed a pronounced cytotoxic effect of the hybrid polymer particles loaded with doxorubicin, indicating their potential for cancer therapies. Furthermore, investigations on doping the hybrid particles with the Ga-68 radioisotope demonstrated their potential application in positron emission tomography (PET) imaging. The proposed structures present a promising theranostic platform, where particles could be employed in anticancer therapies while monitoring their accumulation in the body using PET. [ABSTRACT FROM AUTHOR]