MDA-MB231 Human Breast Cancer Research Articles

Novel quinazolines bearing 1,3,4-thiadiazole-aryl urea derivative as anticancer agents: design, synthesis, molecular docking, DFT and bioactivity evaluations

A novel series of 1-(5-((6-nitroquinazoline-4-yl)thio)-1,3,4-thiadiazol-2-yl)-3-phenylurea derivatives 8 were designed and synthesized to evaluate their cytotoxic potencies. The structures of these obtained compounds were thoroughly characterized by IR, 1H, and 13C NMR, MASS spectroscopy and elemental analysis methods. Additionally, their in vitro anticancer activities were investigated using the MTT assay against A549 (human lung cancer), MDA-MB231 (human triple-negative breast cancer), and MCF7 (human hormone-dependent breast cancer). Etoposide was used as a reference marketed drug for comparison. Among the compounds tested, compounds 8b and 8c demonstrated acceptable antiproliferative activity, particularly against MCF7 cells. Considering the potential VEGFR-2 inhibitor potency of these compounds, a molecular docking study was performed for the most potent compound, 8c, to determine its probable interactions. Furthermore, computational investigations, including molecular dynamics, frontier molecular orbital analysis, Fukui reactivity descriptor, electrostatic potential surface, and in silico ADME evaluation for all compounds were performed to illustrate the structure–activity relationship (SAR).

Mycosynthesis of Zinc Oxide Nanoparticles Coated with Silver using Ganoderma lucidum (Curtis) P. Karst and Its Evaluation of In Vitro Antidiabetic and Anticancer Potential

Nanotechnology is an evolving interdisciplinary field of research interspersing material science and nanobiotechnology. Nanoparticles are studied extensively for their specific catalytic, magnetic, electronic, optical, antimicrobial, theranostic, diagnosis, wound healing, and anti-inflammatory properties. ZnO nanoparticles (NPs) have many applications owing to their unique characteristics, which include low cost, nontoxicity, abundance in nature, and the ability to prepare compounds with varying morphologies having different properties. The main aim of the study is to biosynthesis of ZnO nanoparticles coated with silver from the aqueous extract of Ganoderma lucidum (Curtis) P. Karst and to evaluate its antidiabetic potential by performing alpha-glucosidase inhibition and alpha-amylase inhibition assays and to evaluate the anticancer potential by cytotoxicity (MTT) assay against human breast cancer MDA-MB 231 cell lines. The biosynthesis of ZnO nanoparticles coated with Ag was characterized by UV–vis spectroscopy, Fourier transform infrared spectroscopy, energy dispersive X-ray analysis, scanning electron microscope, and transmission electron microscopy. An increasing concentration in the biosynthesized ZnO nanoparticles coated with Ag produces strong antidiabetic activity through enzyme inhibition effect and anticancer activity through the reduction of cell viability. The present study recommended that the “Biological” method of biological nanoparticle production is a promising approach that allows synthesis in aqueous conditions, with low energy requirements and low costs. In the future, the mycosynthesized nanoparticles might be used in the medical arena to treat and prevent diseases.

Visualizing Activated Myofibroblasts Resulting from Differentiation of Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) are multipotent cells that exhibit two main characteristics which define stem cells: self-renewal and differentiation. MSCs can migrate to sites of injury, inflammation, and tumor. Moreover, MSCs undergo myofibroblast-like differentiation, including increased production of α-SMA in response to transforming growth factor-β (TGF-β), a growth factor commonly secreted by tumor cells to evade immune surveillance. Based on our previous findings, hMSCs become activated and resemble carcinoma-associated myofibroblasts upon prolonged exposure to a conditioned medium from MDAMB231 human breast cancer cells. In this section, we show using immunofluorescence that keratinocyte-conditioned medium (KCM) induces differentiation of MSCs to resemble dermal myofibroblast-like cells with punctate vinculin staining and F-actin filaments.

Zn(II)-dicarboxylato-terpyridyl coordination polymer - A ‘Turn on’ fluorogenic platform for Al3+ sensing in aqueous medium and life cell imaging

Recently, coordination polymers (CPs/MOFs) have emerged as a desirable hybrid material for sensing analytes- such as ions, amino acids, nitroexplosives due to their versatility, stability, reusability, economic benefits and sustainability. Herein, [Zn(bdc)(4-Cltpy)(H2O)]n (CP) [4-Cltpy = 4′-Chloro-2,2′:6′,2′′-terpyridine, H2bdc = Benzene-1,4-dicarboxylic acid], a coordination polymer, is structurally characterized. The structure reveals that the bdc2− bridges Zn(II) via dicarboxylato-O and propagates to form a 1D Coordination Polymer. The 1D CP further undergoes Cl⋯Cl interaction to form a 2D sheet and H-bonding and π⋅⋅⋅π interactions help to construct a 3D supramolecular architecture. Photoluminescence study exposes that the CP is weakly emissive while the fluorescence intensity is significantly enhanced upon interaction with Al3+ in aqueous medium even in presence of quenchable ions like Fe3+ and Cr3+. The detection limit (LOD) is 0.2 ± 0.005 µM (3σ/M method) which is much lower than the permissible limit in drinking water recommended by U.S. Environmental Protection Agency (0.2 mg/L or 7.4 µM). The toxicity of CP has been checked by MTT Assay and intracellular imaging of Al3+ is vivid in human breast cancer MDA-MB 231 cells. The reagent is used for real water sample analysis by fluorescence spectroscopic technique.

Cichorium intybus bio-callus synthesized silver nanoparticles: A promising antioxidant, antibacterial and anticancer compound

Cichorium intybus, commonly called chicory, has been widely used as a coffee substitute. It display a wide range of natural compounds and medicinally uses in treatment of gastrointestinal disorders. This study synthesized silver nanoparticles (Ci-AgNPs) using C. intybus leaf-derived callus extract to evaluate phytochemical content, antibacterial, antioxidant and anti-proliferative activities against human breast cancer cells (MDA-MB231). The optimal shape, size and stability of Ci-AgNPs was confirmed using UV–visible spectrophotometry, FESEM, EDX, XRD, DLS, Zeta potential, FTIR and sp-ICP-MS studies. The antibacterial activity of Ci-AgNPs was assessed using disk diffusion method against Staphylococcus aureus and Escherichia coli, and they displayed distinct zones of inhibition. Colorimetric phytochemical analysis of Ci-AgNPs revealed their higher total phenolic (TP) and total flavonoid (TF) content. Ci-AgNPs also indicated a high level of antioxidant activity using FRAP and DPPH assays. The Ci-AgNPs were investigated for their anticancer activities on the cancerous MDA-MB231 cells viability and apoptosis using MTT and flow cytometry, respectively. Ci-AgNPs showed dose dependent cytotoxicity against MDA-MB231 cells with IC50 value of 187.6 μg/mL at 48 h through induction of apoptosis. The biocompatibility test showed that Ci-AgNPs induced neglectable cytotoxicity (lower than 3 %) toward human erythrocytes. This is the first study that reports the bio-callus mediated synthesis of silver nanoparticle using C. intybus callus extract which provided a promising anticancer activity against human breast cancer MDA-MB231 cells and therefore could be used as an alternative and interesting benign strategy for biosynthesis of silver nanoparticles useful in cancer therapy.

The comparative study of growth and drug response of MCF-7 and MDA-MB231 human breast cancer cells in two- and three-dimensional culture

هدف: کشت سه بعدی سلولهای سرطانی، روشی است که در آن سلول‌ها فرصت رشد و ارتباط همه جانبه در یک فضای سه بعدی داشته و توده های سلولی با نام توموسفر ایجاد می‌کنند. در سالهای اخیر، توسعه مدل های توموری از سلول های سرطانی با به‌کارگیری روش های کشت سه بعدی به عنوان استراتژی دقیق و قابل اعتماد جهت مطالعه سلول های بنیادی سرطانی و شناسایی رویکردهای درمانی مبتنی بر سلول بنیادی سرطانی شناخته می شود. مدلهای سه­بعدی در مقایسه با روش مرسوم کشت تک لایه، شباهت بیشتری به شراط درون تنی دارند. زیرا در مدلهای توموری، ریزمحیط توموری، تعاملات سلول-سلول و سلول-ماتریکس خارج سلولی و شرایط هیپوکسی که لازمه بقا سلول های بنیادی سرطان است به خوبی بازتولید می شود. مدلهای توموری از طریق بکارگیری چندین گونه سلولی از جمله سلولهای سرطانی و استرومایی در ساخت، به خوبی قابلیت توسعه و بازتاب پیچیدگی بافتی را دارند که در چنین حالتی، حتی مدلی دقیقتر در بازتاب شرایط وقعی بدن محسوب می شوند. ازینرو در مطالعه حاضر، ساخت مدل سه بعدی سرطان پستان با هدف بررسی ارتباط رفتار سلولی با شرایط کشت (دوبعدی و سه بعدی)، مطالعه مقایسه‌ای رشد و پاسخ دارویی دو رده سلول سرطان پستان انسانی انجام شده است. مواد و روش­ها: دو رده سلولی MCF-7 و MDA-MB-231 به صورت دو بعدی و سه بعدی (به دو شیوه کشت در سطح و کشت غوطه ور) بر روی داربست ماتریژل کشت داده شدند. فنوتیپ مولکولی سلول‌ها بر حسب مارکرهای سطحی با استفاده از روش فلوسایتومتری بررسی شد. رشد ماموسفرها در 12 روز دنبال و کنتیک رشد آنها مشخص شد. برای بررسی پاسخ دارویی دو داروی ضدسرطان اکتینومایسین دی و پکلی تاکسل مورد استفاده قرار گرفت. ابتدا مقادیر IC50 دو دارو برای رده های سلولی مورد مطالعه تعیین شد، سپس ماموسفرهای تولید شده با دوز مشخص دارو تیمار و اثر آنها بر رشد ماموسفرها دنبال شد. نتایج: دو رده سلولی MCF-7 و MDA-MB-231 که بهصورت دو بعدی و سه بعدی کشت داده شدند تفاوت معنیداری در فنوتیپ مولکولی نشان می‌دهند. به گونه ای که بنظر میرسد پس از کشت سه بعدی بیان مارکر سطحی CD44 بطور قابل توجهی کاهش داشته است. از طرفی ویژگی‌های رشدی سلولهای مورد مطالعه در دو حالت مختلف کشت سه بعدی اختلاف قابل توجهی نشان می‌دهند. مطالعات پاسخ دارویی نیز به‌طور مشابه گویای اختلاف پاسخ دارویی در شرایط کشت دو بعدی و سه بعدی است به گونه ای که اثر مهارکنندگی داروی پکلی‌تاکسل در مقایسه با داروی اکتینومایسین دی، در شرایط کشت سه بعدی کاهش داشته است. علاوه بر آن نتایج نشان می‌دهند که دو رده MCF-7 و MDA-MB231 نیز پاسخ دارویی متفاوتی دارند که میتواند متاثر از فنوتیپ مولکولی متفاوت آنها باشد. نتیجه­گیری: در مجموع نتایج حاصل از پژوهش انجام شده, موید این نکته است که فنوتیپ مولکولی سلول‌های سرطانی، ویژگی‌های رشدی و پاسخ دارویی آنها بهشدت متاثر از نوع رده سلولی مورد مطالعه، شیوه کشت آنها و نوع داروی بهکار رفته است. بنابراین انجام هرچه دقیق‌تر مطالعات سرطانی مستلزم دستیابی به مدلی است که بیشترین شباهت را با تومور مربوطه در بدن داشته باشد.

Nutritional Value and Biological Activities of Sea Cucumber Holothuria scabra Cultured in the Open Pond System

ABSTRACT The aim of this study was to investigate the production of H. scabra in an open pond culture system and to evaluate the nutritional value and biological activities. H scabra in this study was successfully grown with an average size 15.3 cm and weight 132.7 g after an eight month period. The H. scabra cultured was rich in protein content (73.41%). The extracts obtained from the soxhletation method showed potential antioxidant and anticancer activity against MDA-MB-231 breast cell cancer lines, with the greatest antioxidant activity of 5.97 ± 0.95 TEAC (based on the ABTS method). The activity is related to the highest total flavonoid content (249.96 mg QE/100 g). The soxhlet and maceration extracts also showed potent cytotoxic activity against human breast cancer MDA-MB 231. These data indicated that by culturing H. scabra in an open pond system could provide a high quality of sea cucumber in terms of biomass yield and biological activity.

A novel 3D co-culture platform for integrating tissue interfaces for tumor growth, migration and therapeutic sensitivity: “PP-3D-S”

Metastatic cancers can be highly heterogeneous, show large patient variability and are typically hard to treat due to chemoresistance. Personalized therapies are therefore needed to suppress tumor growth and enhance patient's quality of life. Identifying appropriate patient-specific therapies remains a challenge though, due mainly to non-physiological in vitro culture systems. Therefore, more complex and physiological in vitro human cancer microenvironment tools could drastically aid in development of new therapies. We developed a plasma-modified, electro-spun 3D scaffold (PP-3D-S) that can mimic the human cancer microenvironment for customized-cancer therapeutic screening. The PP-3D-S was characterized for optimal plasma-modifying treatment and scaffolds morphology including fiber diameter and pore size. PP-3D-S was then seeded with human fibroblasts to mimic a stromal tissue layer; cell adhesion on plasma-modified poly (lactic acid), PLA, electrospun mats vastly exceeded that on untreated controls. The cell-seeded scaffolds were then overlaid with alginate/gelatin-based hydrogel embedded with MDA-MB231 human breast cancer cells, representing a tumor-tissue interface. Among three different plasma treatments, we found that NH3 plasma promoted the most tumor cell migration to the scaffold surfaces after 7 days of culture. For all treated and non-treated mats, we observed a significant difference in tumor cell migration between small-sized and either medium- or large-sized scaffolds. In addition, we found that the PP-3D-S was highly comparable to the standard Matrigel® migration assays in two different sets of doxorubicin screening experiments, where 75% reduction in migration was achieved with 0.5 μM doxorubicin for both systems. Taken together, our data indicate that PP-3D-S is an effective, low-cost, and easy-to-use alternate 3D tumor migration model which may be suitable as a physiological drug screening tool for personalized medicine against metastatic cancers.

Vitamin D3/phospholipid complex decorated caseinate nanomicelles for targeted delivery of synergistic combination therapy in breast cancer

Targeted delivery of cytotoxic drugs has shown great potential in cancer therapy. In this light, vitamin D3 (vit.D3)-coated micelles were fabricated to encapsulate the cytotoxic drug; etoposide (ETP). Sodium caseinate micelles were first utilized to encapsulate vit.D3 and ETP within their hydrophobic core, then drug-loaded micelles were further decorated with an envelope of vit.D3/ phospholipid complex to enhance the active targeting potency of fabricated micelles via exploiting vit.D3 receptors (VDRs) overexpressed on the outer surface of breast cancer cells. In vitro cytotoxicity studies showed that fabricated micelles exhibited improved anticancer effect on MDA MB-231 and MCF-7 human breast cancer cell lines in comparison to free vit.D3 + ETP without any significant toxicity on normal human lung fibroblast (Wi-38) cells. In vivo biodistribution and efficacy studies in Ehrlich ascites tumor animal model revealed that fabricated micelles manifested improved accumulation in tumor tissue due to active targeting potential of vit.D3 without any remarkable toxicity. More importantly, fabricated micelles resulted in enhanced tumor apoptosis, reduced angiogenesis, invasion and autophagy, besides a decline in the tumor expression levels of both miR-21 and miR-192. Therefore, vit.D3/ETP micelles could serve as a favorable actively targeted anticancer delivery system having a superior effect over the free combination.

Effects of curcumin-loaded poly(lactic-co-glycolic acid) nanoparticles in MDA-MB231 human breast cancer cells.

Aim: This study was aimed at evaluating the anticancer potential of curcumin-loaded poly(lactic-co-glycolic acid) (PLGA) based nanoparticles (NPs) in MDA-MB231 human breast cancer cells. Methods: Curcumin-loaded PLGA NPs were developed using a modifiedsolvent evaporation technique. Physical characterization was performed on the formulated NPs. Furthermore, in vitro experiments were conducted to study the biological activity of the curcumin-loaded NPs. Results: Curcumin-loaded PLGA NPs demonstrated high encapsulation efficiency and sustained payload release. Moreover, the NPs exhibited a significant reduction in cell viability, cell migration and cell invasion in the MDA-MB231 cells. Conclusion: The study revealed that the formulated curcumin-loaded PLGA NPs possessed significant anti-metastatic properties. The findings showcased the possible potential of curcumin-loaded NPs in the management of debilitating conditions such as cancer. In addition, this study could form the basis for further research and advancements in this area.

Distinct rhodamine B derivatives exhibiting dual effect of anticancer activity and fluorescence property

Design and application of novel Rhodamine B amide derivatives achieved especially with simple secondary amines, and furthermore exhibiting fluorescence property and anticancer activity is not reported elsewhere. Further functionalization of rhodamine B at the carboxylic acid group with selected secondary amines generated amides, avoiding cyclization and simultaneously sustaining fluorescence. Currently, we have designed and developed three well defined novel rhodamine B amide derivatives by reacting rhodamine B (RHB) with thiomorpholine, bis-(2-chloroethyl) amine and morpholine (the side chains of several anticancer drugs) via rhodamine B acid chloride which resulted in fluorophores namely rhodamine B thiomorpholine amide (1), rhodamine B bis(2-chloroethyl)amine amide (2) and rhodamine B morpholine amide (3). All the three RHB amides were thoroughly characterized using analytical techniques like FT-IR, Mass, 1H NMR, 13C NMR spectroscopy and HPLC. Obtained compounds displayed molecular material attributes as well as anticancer activity. The wavelength of maximum absorption and emission of solutions occurred at ~560 nm and ~583 nm. Quantum yields (Φf = 0.40) and average fluorescence decay (~1.60 ns) of amides was comparable to RHB (1.72 ns). Optical bandgap of solids revealed semiconducting property (~ 2.9 eV). Acquired rhodamine B amides were found to be insensitive over a wide range of pH i.e. from 2 to 10 suggesting their plausible utility in biological labeling, moreover, showed potential anticancer activity against B16F10 (murine melanoma cells), MDA-MB231 (human breast cancer cells), A549 (human lung cancer cells) while they displayed less toxicity to normal HEK 293 (human embryonic kidney) cells. Interestingly, the cellular uptake study manifested that more quantity of the compound were taken up by the cancer cells compared to normal cells which indicate that these amides might become potential candidates to be developed as theranostic agents.

Phytochemical, elemental, physico-chemical, HPTLC and anticancer investigations of Ceropegia spiralis Wight. Tuber extracts

Phytochemical constituents are responsible for medicinal activity of plant species. Hence in the present study Qualitative and quantitative phytochemical screening, Physicochemical, elemental analysis and anticancer activity of Ceropegia spiralis tuber extracts were carried out. Qualitative and quantitative phytochemical analysis of tuber aqueous extract confirm the presence of various secondary metabolites like saponins, triterpenoids, steroids, tannins, alkaloids, flavonoids and phenols. The results suggest that the phytochemical properties for curing various ailments and possess potential anticancer, antimicrobial and antioxidant activities leads to the isolation of new and novel compounds. Physicochemical studies reveals that the dry matter 96.23%; followed by Water soluble extractive 14.28 %. Elemental analysis reveals Nitrogen 3.4 % followed by Zinc 218.9%. Along with this, macro and micro elements which are essential for maintaining the animal body were also determined quantitatively. Anticancer activity of C. spiralis exhibited potential towards MDAMB-231 (human breast cancer) cell lines, shows 78.30% cell death with cell viability 21.70% at 100 µg/ml. The presence of various bioactive compounds confirms the application of C. spiralis against many ailments by the traditional practitioners.

Synthesis and anticancer activities of some new coumarin derivatives including the triazole ring and their in silico molecular docking studies.

The synthesis, docking study, and investigation of the anticancer activities of some coumarin derivatives containing the triazole ring are reported in this study. The newly synthesized compounds were screened for their in vitro anticancer activity against the cell lines CRL5807 (human bronchioalveolar carcinoma), CRL5826 (human squamous cell carcinoma), MDA-MB231 (human breast cancer cells), HTB177 (human lung cancer), PC-3 (human prostate adenocarcinoma), PANC-1 (human pancreatic cancer cells), used as cancer cells, and CCD34Lu (normal human lung fibroblasts), used as a healthy cell line. Cytotoxicity effects of the samples were determined by the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay. In silico studies were also performed to explore the binding interactions of the molecules.

Assessment of replication of bovine herpesvirus type 4 in human glioblastoma and breast cancer cells as a potential oncolytic virus.

Oncolytic viruses have been extensively used in cancer treatment due to their tropism, selective replication only in tumor cells, and possible synergic interaction with other therapeutics. Different researchers have demonstrated that bovine herpesvirus 4 (BoHV-4), a member of the gammaherpesviridae family, has oncolytic potential in some human-origin cancer cell lines like glioma through the selective replication strategy. Using four apoptosis detection methods, namely MTT, LDH, TUNEL, and Annexin V assays, we evaluated the apoptotic effect of BoHV-4 Movar33/63 reference strain along with a recombinant BoHV-4 expressing EGFP in U87 MG cells (human glioblastoma cell line), MDA MB-231 (human breast cancer cell line), and MCF10a (non-tumorigenic human mammary epithelial cell line). Our findings indicate that this virus can replicate and induce apoptosis in these cell lines and hinder in vitro proliferation in a dose-dependent manner. In conclusion, BoHV-4 has in vitro potential as a novel oncolytic virus in human cancer therapy. However, its replication potential in the MCF10a cells as a non-tumorigenic human mammary epithelial cell line is a concern in using this virus in cancer therapy, at least against human mammary tumors. Further studies must therefore be conducted to examine the specific apoptotic pathways induced by this virus to move on to further experiments.

Ni-Cu Nanoparticles and Their Feasibility for Magnetic Hyperthermia.

Ni-Cu nanoparticles have been synthesized by reducing Ni and Cu from metal precursors using a sol–gel route followed by annealing at 300 °C for 1, 2, 3, 6, 8, and 10 h for controlled self-regulating magnetic hyperthermia applications. Particle morphology and crystal structure revealed spherical nanoparticles with a cubic structure and an average size of 50, 60, 53, 87, and 87 nm for as-made and annealed samples at 300 °C for 1, 3, 6, and 10 h, respectively. Moreover, hysteresis loops indicated ferromagnetic behavior with saturation magnetization (Ms) ranging from 13–20 emu/g at 300 K. Additionally, Zero-filed cooled and field cooled (ZFC-FC) curves revealed that each sample contains superparamagnetic nanoparticles with a blocking temperature (TB) of 196–260 K. Their potential use for magnetic hyperthermia was tested under the therapeutic limits of an alternating magnetic field. The samples exhibited a heating rate ranging from 0.1 to 1.7 °C/min and a significant dissipated heating power measured as a specific absorption rate (SAR) of 6–80 W/g. The heating curves saturated after reaching the Curie temperature (Tc), ranging from 30–61 °C within the therapeutic temperature limit. An in vitro cytotoxicity test of these Ni-Cu samples in biological tissues was performed via exposing human breast cancer MDA-MB231 cells to a gradient of concentrations of the sample with 53 nm particles (annealed at 300 °C for 3 h) and reviewing their cytotoxic effects. For low concentrations, this sample showed no toxic effects to the cells, revealing its biocompatibility to be used in the future for in vitro/in vivo magnetic hyperthermia treatment of cancer.

Design, Synthesis, and Anticancer Activity of Substituted Styryl Incorporated Quinazoline Derivatives

A novel series of substituted aryl ethynyl incorporated quinazolines has been synthesized, and their molecular structures have been characterized by1H and 13C NMR, and mass spectra. The products have been tested for their preliminary anticancer activity against human cancer cell lines like MCF-7 (human breast cancer), A549 (human lung cancer), DU-145 (human prostate cancer), and MDA MB-231 (human breast cancer). Some compounds are characterized by potent activity.

Preparation of Lipid Nano-Bubbles as Contrast Agent Material for Tumor Ultrasound Diagnosis of Breast Cancer

Ultrasound diagnostic technology has higher application values in tumor diagnosis due to its higher spatial resolution and no radiation. Ultrasound lipid nanobubble contrast material can further improve the accuracy of tumor diagnosis. Therefore, the liposomes were used as shells to encapsulate bio-inert gases to prepare nano-scale microbubbles NBs. Meanwhile, the Annexin V molecules were connected through the conjugation of biotin-avidin to prepare targeted nano-scale ultrasound contrast agents (UCAs) Annexin V-Nanobubbles (AVNBs). The tumor-bearing mice apoptosis models were constructed by injecting human breast cancer MDA-MB231 cells, and the nano-scale UCA AV-NBs was used for ultrasound diagnosis, data collection, and statistical analysis. The results showed that the prepared AV-NBs were nano-sized hollow spheres with relatively stable particle size, zeta potential, and excellent stability. By verifying the constructed mice apoptosis models, it was found that mice heterotopic transplantation tumor apoptosis models were successfully constructed. When the mice models were observed by ultrasound, the apoptosis index of the cell was found to be positively correlated with the enhancement degree of the image. Therefore, the enhancement effect of the targeted UCA AV-NBs was obvious. The AV-NBs could be specifically targeted to the apoptotic region of tumor tissue in vivo, which was also slightly enriched in the liver and kidney. Therefore, the experiment found that the targeted nano-scale UCA AV-NBs combined with ultrasound detection could significantly enhance the diagnostic accuracy of breast cancer tumors, which provided the experimental evidence for early tumor diagnosis and evaluation.

Quantitative label-free imaging of iron-bound transferrin in breast cancer cells and tumors

Transferrin (Tf) is an essential serum protein which delivers iron throughout the body via transferrin-receptor (TfR)-mediated uptake and iron release in early endosomes. Currently, there is no robust method to assay the population of iron-bound Tf in intact cells and tissues. Raman hyperspectral imaging detected spectral peaks that correlated with iron-bound Tf in intact cells and tumor xenografts sections (~1270-1300 cm−1). Iron-bound (holo) and iron-free (apo) human Tf forms were endocytosed by MDAMB231 and T47D human breast cancer cells. The Raman iron-bound Tf peak was identified in cells treated with holo-Tf, but not in cells incubated with apo-Tf. A reduction in the Raman peak intensity between 5 and 30 min of Tf internalization was observed in T47D, but not in MDAMB231, suggesting that T47D can release iron from Tf more efficiently than MDAMB231. MDAMB231 may display a disrupted iron homeostasis due to iron release delays caused by alterations in the pH or ionic milieu of the early endosomes. In summary, we have demonstrated that Raman hyperspectral imaging can be used to identify iron-bound Tf in cell cultures and tumor xenografts and detect iron release behavior of Tf in breast cancer cells.

Design and Synthesis of Arylnaphthalene Lignan Lactone Derivatives as Potent Topoisomerase Inhibitors.

Arylnaphthalene lignan lactones are a class of natural products containing the phenyl-naphthyl skeleton. Some arylnaphthalene lignan lactones have been used in clinical practice as antitumor agents, due to their cytotoxicity and inhibitory activities against DNA topoisomerase I (Topo I) and topoisomerase II (Topo II). This study presents the design and synthesis of arylnaphthalene lignan lactones derivatives. The inhibitory activities against Topo I and Topo IIα and antitumor activities of these compounds were assayed. A series of arylnaphthalene lignan lactones derivatives have been designed and synthesized, using the Diels-Alder reaction and Suzuki reaction as the key steps. Their antiproliferation activities were evaluated by sulforhodamine B assay on human breast cancer MDAMB-231, MDA-MB-435 and human cervical cancer HeLa cells. DNA relaxation assays were employed to examine the inhibitory activity of compounds 1-22 on Topo I and Topo IIα in vitro. Flow cytometry analysis was performed to study the drug effects on cell cycle progressions. Seven compounds exhibited the modest anti-proliferation activity with IC50 values between 1.36 and 20 μM. Compounds 3, 19 and 22 showed potent inhibitory activities with IC50 values less than 1 μM. DNA relaxation assay revealed that compound 22 showed potent inhibitory activity against Topo IIα in vitro. Compound 22 also induced DNA breaks in MDA-MB-435 cells evidenced by comet tails and the accumulation of γ-H2AX foci. The ability of 22 in inducing DNA breaks mediated by Topo IIα resulted in G2/M phase arrest and apoptosis. This work indicates that arylnaphthalene lignan lactones derivatives represent a novel type of Topo IIα inhibitory scaffold for developing new antitumor chemotherapeutic agents.

Oligo-Fucoidan Prevents M2 Macrophage Differentiation and HCT116 Tumor Progression

Reactive oxygen species (ROS) produced during intracellular metabolism or triggered by extrinsic factors can promote neoplastic transformation and malignant microenvironment that mediate tumor development. Oligo-Fucoidan is a sulfated polysaccharide isolated from the brown seaweed. Using human THP-1 monocytes and murine Raw264.7 macrophages as well as human HCT116 colorectal cancer cells, primary C6P2-L1 colorectal cancer cells and human MDA-MB231 breast cancer cells, we investigated the effect of Oligo-Fucoidan on inhibiting M2 macrophage differentiation and its therapeutic potential as a supplement in chemotherapy and tumor prevention. We now demonstrate that Oligo-Fucoidan is an antioxidant that suppresses intracellular ROS and mitochondrial superoxide levels in monocytes/macrophages and in aggressive cancer cells. Comparable to ROS inhibitors (DPI and NAC), Oligo-Fucoidan directly induced monocyte polarization toward M1-like macrophages and repolarized M2 macrophages into M1 phenotypes. DPI and Oligo-Fucoidan also cooperatively prevented M2 macrophage invasiveness. Indirectly, M1 polarity was advanced particularly when DPI suppressed ROS generation and supplemented with Oligo-Fucoidan in the cancer cells. Moreover, cisplatin chemoagent polarized monocytes and M0 macrophages toward M2-like phenotypes and Oligo-Fucoidan supplementation reduced these side effects. Furthermore, Oligo-Fucoidan promoted cytotoxicity of cisplatin and antagonized cisplatin effect on cancer cells to prevent M2 macrophage differentiation. More importantly, Oligo-Fucoidan inhibited tumor progression and M2 macrophage infiltration in tumor microenvironment, thus increasing of anti-tumor immunity.