MCF-7 Human Breast Cancer Research Articles

A Pyridyl-Linked Benzimidazolyl Tautomer Facilitates Prodigious H+/Cl- Symport through a Cooperative Protonation and Chloride Ion Recognition.

We report two pyridyl-linked benzimidazolyl hydrazones as HCl cotransporters that are 5 and 2 times superior to prodigiosin, a natural product whose transport efficiency has never been routed by synthetic molecules. These hydrazones provide a suitable HCl binding site through a cooperative protonation and chloride ion recognition. HCl transport by the most active compound induces lysosome deacidification. Viability assays confirmed that the compounds induce cytotoxicity toward human breast cancer MCF-7 cells but are relatively nontoxic toward noncancerous HEK293T cells.

Anticancer activity of gold nanobioconjugates synthesized from Elephantopus scaber (linn.) leaf extract.

Medicinal plants are the major natural resources for the treatment of human ailments including cancer therapy. The current cancer treatments such as surgery, radiation, and chemotherapy affect normal cells too. Thus, treatments like synthesized nanoscale particles using plant extracts have proven to be potential anticancer agent. We hypothesize that the gold nanoparticles (AuNPs) synthesized using Elephantopus scaber hydro-methanolic extract may have anti-cancer activity along with their synergistic counterparts with adriamycin (ADR) on human breast cancer MCF-7: human breast cancer (A-549), human oral cancer (squamous cell carcinoma [SCC]-40), and COLO-205: human colon cancer cell lines. The phytosynthesized AuNPs were characterized for ultraviolet-visible (UV-Vis) spectroscopy, nanoparticle tracking analysis (NTA), X-ray diffraction, scanning electron microscopy, transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) analysis. The anticancer ability of the AuNPs against human MCF-7, A-549, SCC-40, and COLO-205 through sulforhodamine B assay has been studied. The synthesis of AuNPs was confirmed with the UV-Vis spectrophotometer with a peak at 540 nm. The FTIR analysis showed polyphenolic groups were major found to be the reduction and capping agent for AuNPs. According to the results obtained, AuNPs showed good anti-proliferative activity with GI50 <10 μg/ml on MCF-7 cancer cell line. The synergistic effect of AuNPs + ADR was even better for all the four cell lines than that of the AuNPs alone. The green synthesis of AuNPs is a simple, eco-friendly, and cost-effective method with dominantly spherical morphology ranging from 20 to 40 nm confirmed by NTA and TEM analysis. The study reveals the potent therapeutic value of the AuNPs.

VALD-3, a Schiff base ligand synthesized from o-vanillin derivatives, induces cell cycle arrest and apoptosis in breast cancer cells by inhibiting the Wnt/\u03b2-catenin pathway

Schiff base compounds and their metal complexes have become important synthetic organic drugs due to their extensive biological activities, which include anticancer, antibacterial and antiviral effects. In this study, we investigated the cytotoxic and apoptotic effects of VALD-3, a Schiff base ligand synthesized from o-vanillin derivatives, on human breast cancer cells and the possible underlying mechanisms. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-test was used to observe the proliferation of human breast cancer MCF-7 and MDA-MB-231 cells induced by VALD-3. Flow cytometry analysis showed that VALD-3 triggered cell cycle arrest and induced apoptosis of breast cancer cells. Western blot analysis revealed that VALD-3 upregulated pro-apoptotic proteins (Bad and Bax), downregulated anti-apoptotic proteins (Bcl-2, Bcl-xl, survivin and XIAP) and increased the expression of cleaved caspase-3, cleaved caspase-8, Cyto-c and cleaved PARP. VALD-3 also regulated the Wnt/β-catenin signaling pathway in breast cancer cells, inhibiting the activation of downstream molecules. By xenografting human breast cancer cells into nude mice, we found that VALD-3 significantly suppressed tumor cell growth while showing low toxicity against major organs. In addition, survival analysis showed that VALD-3 can significantly prolong the survival time of mice (P = 0.036). This study is the first to show that VALD-3 induces apoptosis and cell cycle arrest in human breast cancer cells by suppressing Wnt/β-catenin signaling, indicating that it could be a potential drug for the treatment of breast cancer.

Development and in vitro evaluation of pH-sensitive naringenin@ZIF-8 polymeric micelles mediated by aptamer

In this study, a pH-sensitive and aptamer-modified drug-loading polymer micelles were designed and synthesized based on the natural plant extract of naringenin(NAR), and further evaluated the drug delivery system in vitro. First of all, the optimal preparation process of (NAR@ZIF-8)/PMs was obtained by Box-Behnken effect surface method. It showed that the regular spherical shape and good dispersion with the transmission electron microscope (TEM). More specifically, the particle size was 239.8 ± 0.76 nm. The zeta potential was −8.9 ± 0.14 mV. The release of AP-(NAR@ZIF-8)/PMs was tested in different pH dissolution media, and the results showed that AP-(NAR@ZIF-8)/PMs could be rapidly released 91.4% within 48 h in the dissolution media with pH = 5.0. It indicated AP-(NAR@ZIF-8)/PMs had superior pH-sensitive release ability. Secondly, AP-(NAR@ZIF-8)/PMs modified with aptamers were prepared by coupling reaction. The results of UV spectroscopy, particle size, zeta potential, X-ray diffraction (XRD) and fourier transform infrared spectroscopy (FTIR) all showed that the aptamer AS1411 had been successfully modified on the surface of (NAR@ZIF-8)/PMs. The MTT method was used to study the in vitro anti-tumor effects of AP-(NAR@ZIF-8)/PMs on human lung cancer A549 cells and human breast cancer MCF-7 cells. Cytotoxicity and proliferation tests showed that AP-(NAR@ZIF-8)/PMs had significant inhibitory effects on human lung cancer A549 cells and human breast cancer MCF-7 cells. The MTT tests confirmed AP-(NAR@ZIF-8)/PMs had obvious targeting effect on human lung cancer A549 cells and human breast cancer MCF-7 cells. In conclusion, this study showed that AP-(NAR@ZIF-8)/PMs achieves the synergism of tumor targeting and pH-sensitive drug release, and provides a new idea for the treatment of malignant tumors.

Combination Effect of Tamoxifen and Ascorbic Acid Treatment on Breast Cancer Cells (MCF-7) and Cervical Cancer Cells (HeLa)

Breast cancer and cervical cancer are among the leading causes of death among women in the world. The development of drug resistance in both cancer cells, has reduced the efficacy of chemotherapeutic drugs in cancer treatment. The current study was aimed to evaluate cell viability of human breast cancer cells, MCF-7 and cervical cancer cells, HeLa upon combination treatment of ascorbic acid and tamoxifen. The cell viability was performed using MTT assay incubated for 72 hours in humidified CO 2 incubator. The concentration of tamoxifen and ascorbic acid that reduced 50% of cells population (IC 50 ) was determined from dose response curve. IC 50 concentration was used to determine cell viability in treated cells. CompuSyn software was used to evaluate the combination effects towards both cells upon treatment and results were calculated as combination index (CI). Data were analysed using IBM SPSS Statistics 24. Statistical analysis was performed using independent t-test. The IC 50 value of tamoxifen and ascorbic acid on MCF-7 cells were 14.53 µg/ml and 15.8 µg/ml respectively whereas the IC 50 value of tamoxifen and ascorbic acid on HeLa cells were 11.09 µg/ml and 202.3 µg/ml respectively. Combination of tamoxifen and ascorbic acid exerted greater growth reduction in both cells compared to tamoxifen alone. The results indicated ascorbic acid synergizes the cytotoxic effect of tamoxifen at lower concentrations towards MCF-7 cells with the CI less than 1. However, the combination of tamoxifen and ascorbic acid exerted antagonistic effect in HeLa cells when CI were more than 1. DOI : http://dx.doi.org/10.17576/JSKM-2021-1902-12

Synthesis and Characterization of Gold Nanoparticles from Nostoc sp. strain HKAR-2 and their In Vitro Antibacterial, Antifungal, and Antitumor Potentials

In the present study, gold nanoparticles (AuNPs) have been synthesized through biological methods using the cell-free extracts of cyanobacterium Nostoc sp. strain HKAR-2 isolated from the hot spring of India. To determine morphological, structural, and optical properties of green synthesized AuNPs, UV-VIS spectroscopy, FTIR, X-ray diffraction, scanning electron microscopy (SEM), and transmission electron microscopy-selected area electron diffraction (TEM-SAED) were used. Spectroscopic analysis showed the absorbance peak at 540 nm due to the reduction of Au3+ to Au0 by cyanobacterial extract, which indicated surface plasmon resonance (SPR) of the synthesized AuNPs. Characteristic Bragg peaks at (111), (200), (220), and (311) facets of the face center cubic (fcc) confirmed the crystalline nature of AuNPs in the XRD pattern. FTIR results indicated the role of proteins and amino acids in the reduction of Au3+ to Au0 as well as for the stability of AuNPs. Zeta potential confirmed a charge of -2.39Mv on the AuNPs. SEM and TEM results confirmed the large agglomerated shape of AuNPs with sizes ranging between 10-100 nm. Their antibacterial, antifungal and anticancerous properties were also studied against plant bacterial strains, fungal strains, and MCF-7 cells, respectively. AuNPs also showed dose-dependent cytotoxic activity against human breast cancer MCF-7 cells with IC50 of 250 μg/mL.

Effects of Rhizopus Nigricans Exopolysaccharide on Proliferation, Apoptosis, and Migration of Breast Cancer MCF-7 Cells and Akt Signaling Pathway

Objective. To study the effect of Rhizopus nigricans exopolysaccharide EPS1-1 on the proliferation, apoptosis, and migration of breast cancer MCF-7 cells. Methods. Human breast cancer MCF-7 cells were cultured in vitro and treated with different concentrations of EPS1-1. The effect of EPS1-1 on cell proliferation was tested by the CCK-8 experiment, and the effect of EPS1-1 on cell apoptosis was determined by flow cytometry. And the scratch test was used to detect the impact of EPS1-1 on cell migration. Western blot then was used to measure the expression changes of related proteins in the Akt signaling pathway. Results. Compared with the control group, treatment with EPS1-1 significantly reduced the proliferation, migration, and invasion ability of MCF-7 cells and promoted the apoptosis of MCF-7 cells in a dose-dependent manner. In terms of the underlying mechanism, EPS1-1 can significantly inhibit the phosphorylation of Akt at threonine 308 and serine 473 and cause the expression changes of downstream proliferation-related genes CCND1 and p21, apoptosis-related genes Bcl-2 and Bax, and migration-related genes Vimentin and E-cadherin in terms of their protein levels. Conclusion. EPS1-1 can inhibit the proliferation, migration, and invasion of breast cancer MCF-7 cells and promote the apoptosis of MCF-7 cells by inhibiting the activation of the Akt signaling pathway. Therefore, EPS1-1 can be used as a potential new drug or adjuvant drug for the treatment of breast cancer.

Fatty acid composition, enzyme inhibitory effect, antioxidant and anticancer activity of extract from Saponaria prostrata WILLD. subsp. anatolica HEDGE

This study attempts to evaluate the antioxidant, enzyme inhibitory, and anticancer properties as well as fatty acid compositions of endemic Saponaria prostrata WILLD. subsp. anatolica HEDGE. The gas chromatography-mass spectrometry (GC–MS) was used to determine the fatty acid content of methanol: dichloromethane extract from S. prostrata subsp. anatolica (SPA). Enzymatic activity was measured against acetylcholinesterase, butyrylcholinesterase and α-glucosidase. DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging activity and Ferric reducing antioxidant power assay (FRAP) were conducted to antioxidant properties. The anticancer effect of SPA on human MCF-7 breast cancer and human HCT116 colorectal cancer cell line was evaluated by WST-1 cell viability assay, colony formation assay and wound healing assay. In addition, human VEGF Elisa method was used to determine the anti-angiogenic effect, and the quantitative real-time PCR (qRT-PCR) method on p53, Bax and Bcl-2 mRNA levels were used to evaluate apoptosis. While high amounts of palmitic acid (40.8%), linoleic acid (17.75%) and α-linolenic acid (16.84%) were detected in the SPA, the total amount of unsaturated fatty acid (51.34%) was higher than the total amount of saturated fatty acid (48.66%). SPA displayed the most promising acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and α-glycosidase (AG) inhibitory activities (AChE: IC50: 18.03 µg/mL, BuChE: IC50: 44.24 µg/mL and AG: IC50: 210.85 µg/mL). The half maximum inhibitory concentration (IC50) of SPA in MCF-7 and HCT116 cells was determined as 259.79 µg/mL and 97.24 µg/mL, respectively. In addition, it was determined that SPA suppresses colony formation and wound closure, and suppresses angiogenesis as well as triggering apoptosis at a significant level. It is true that endemic S. prostrata subsp. anatolica is a potential source of functional food ingredients, but more analytical and in vivo experiments are needed to explore further secondary metabolite diversity and pharmacological properties.

Evaluation of antioxidant and anticancer effects of Piper betle L (Piperaceae) leaf extract on MCF-7 cells, and preparation of transdermal patches of the extract

Purpose: To determine the antioxidant and anticancer effects of Piper betle (P. betle) leaf extract on human breast cancer MCF-7 cells, and to develop transdermal patches containing the extract.&#x0D; Methods: The leaf extract of P. betle was prepared by maceration method, and its antioxidant activity was evaluated using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Cytotoxicity and suppression of cell migration (indices of anticancer activity) were also assessed in MCF-7 cells by sulforhodamine B (SRB) and wound healing assays, respectively. Transdermal patches were developed using the casting method, and the resultant patches were evaluated with regard to their physical appearance and mechanical properties before and after a stability test.&#x0D; Results: The extract exhibited antioxidant activity with half-maximal inhibitory concentration (IC50) of 30.0 ± 0.1 µg/mL. It also showed cytotoxicity with an IC50 of 114.3 ± 14.9 µg/mL, and significantly suppressed the migration of MCF-7 cells at a dose of 25 µg/mL. Based on desirable characteristics, patch base formulations containing 4.2 % pectin, 0.4 % hydroxyl propyl methylcellulose (HPMC), 0.4 % polyvinyl pyrrolidine K-90 (PVP-K90) and 3 % propylene glycol (PG) were selected for incorporation into the extract.&#x0D; Conclusion: Leaf extract of P. betle exhibits potential anti-breast cancer properties. A transdermal patch containing 0.03 % of the extract can be successfully developed for treatment of breast cancer.

Design, synthesis and structure–activity relationships of novel N11-, C12- and C13-substituted 15-membered homo-aza-clarithromycin derivatives against various resistant bacteria

Bacterial infections are still the main significant problem of public health in the world, and their elimination will greatly rely on the discovery of antibacterial drugs. In the processes of our searching for novel macrolide derivatives with excellent activity against sensitive and resistant bacteria, three series of novel N11-, C12- and C13-substituted 15-membered homo-aza-clarithromycin derivatives were designed and synthesized as Series A, B and C by creatively opening the lactone ring of clarithromycin (CAM), introducing various 4-substituted phenyl-1H-1,2,3-triazole side chains at the N11, C12 or C13 position of CAM and macrolactonization. The results from their in vitro antibacterial activity demonstrated that compounds 20c, 20d and 20f displayed not only the most potent activity against S. aureus ATCC25923 with the MIC values of 0.5, 0.5 and 0.5 µg/mL, but also greatly improved activity against B. subtilis ATCC9372 with the MIC values of less than or equal to 0.25, 0.25 and 0.25 µg/mL, respectively. In particular, compound 11g exhibited the strongest antibacterial effectiveness against all the tested resistant bacterial strains and had well balanced activity with the MIC values of 4–8 µg/mL. Further study on minimum bactericidal concentration and kinetics confirmed that compound 11g possessed a bacteriostatic effect on bacterial proliferation. Moreover, the results of molecular docking revealed an potential additional binding force between compound 11g and U790 in addition to the normal binding force of macrolide skeleton, which may explain why this compound performed the most potent activity against resistant bacteria. The results of cytotoxic assay indicated that compounds 20c, 20d and 20f were non-toxic to human breast cancer MCF-7 cells at its effective antibacterial concentration.

Decrease of ABCB1 protein expression and increase of G1 phase arrest induced by oleanolic acid in human multidrug-resistant cancer cells.

Oleanolic acid (OA) is a natural compound that can be found in a number of edible and medicinal plants and confers diverse biological actions. However, the direct target of OA in human tumor cells remains poorly understood, preventing its application in clinical and health settings. A previous study revealed that overexpression of caveolin-1 in human leukemia HL-60 cells can increase its sensitivity to OA. The present study aimed to investigate the effects of OA on the doxorubicin-resistant human breast cancer MCF-7 cell line (MCF-7/DOX), harringtonine-resistant human leukemia HL-60 cells (HL-60/HAR) and their corresponding parental cell lines. Western blotting was performed to measure protein expression levels, whilst Cell Counting Kit-8 (CCK-8) assays, cell cycle analysis (by flow cytometry) and apoptosis assays (with Annexin V/PI staining) were used to assess drug sensitivity. CCK-8 assay results suggested that MCF-7/DOX cells, which overexpress the caveolin-1 protein, have similar OA susceptibility to their parent line. In addition, sensitivity of MCF-7/DOX cells to OA was not augmented by knocking down caveolin-1 using RNA interference. HL-60/HAR cells exhibited a four-fold increased sensitivity to OA compared with that in their parental HL-60 cells according to CCK-8 assay. Both of the resistant cell lines exhibited higher numbers of cells at G1 phase arrest compared with those in their parent lines, as measured via flow cytometry. Treatment of both MCF-7 cell lines with 100 µM OA for 48 h induced apoptosis, with increased effects observed in resistant cells. However, no PARP-1 or caspase-3 cleavage was observed, with some positive Annexin V staining found after HL-60/HAR cells were treated with OA, suggesting that cell death occurred via non-classical apoptosis or through other cell death pathways. It was found that OA was not a substrate of ATP-binding cassette subfamily B member 1 (ABCB1) in drug-resistant cells, as indicated by the accumulation of rhodamine 123 assessed using flow cytometry. However, protein expression of ABCB1 in both of the resistant cell lines was significantly decreased after treatment with OA in a concentration-dependent manner. Collectively, these results suggest that OA could reduce ABCB1 protein expression and induce G1 phase arrest in multidrug-resistant cancer cells. These findings highlight the potential of OA for cancer therapy.

Silver Nanoparticle-Coated Ethyl Cellulose Inhibits Tumor Necrosis Factor-α of Breast Cancer Cells.

IntroductionCancer is one of the leading causes of death worldwide. In many cases, cancer is related to the elevated expression of a significant cytokine known as tumor necrosis factor-α (TNF-α). Breast cancer in particular is linked to increased proliferation of tumor cells, high incidence of malignancies, more metastases, and generally poor prognosis for the patient. The research sought to assess the effect of silver nanoparticles reduced with ethyl cellulose polymer (AgNPs-EC) on TNF-α expression in MCF-7 human breast cancer cells.MethodsThe AgNPs-EC were produced using the green synthesis reduction method, and their formation was proofed via UV–VIS spectroscopy. Furthermore, AgNPs-EC were characterized for their size, charge, morphology, Ag ion release, and stability. The MCF-7 cells were treated with AgNPs-EC. Then, the expression of TNF-α genes was determined through PCR in real time, and protein expression was studied using ELISA.ResultsThe AgNPs-EC were spherical with an average size of 150±5.1 nm and a zeta-potential of −41.4±0.98 mV. AgNPs-EC had an inhibitory effect on cytokine mRNA and protein expression levels, which suggests that they could be used safely in the fight against cancer. AgNPs-EC cytotoxicity was also found to be non-toxic to MCF-7.ConclusionOur data determined AgNPs-EC as a novel inhibitor of TNF-α production. These results are promising for developing novel therapeutic approaches for the future treatment of cancer with safe materials.

Ginsenoside Rh1 Induces MCF-7 Cell Apoptosis and Autophagic Cell Death through ROS-Mediated Akt Signaling.

Simple SummaryBreast cancer (BC) is the most common cause of cancer-related deaths among women worldwide, and its incidence has been increasing. However, current therapeutic approaches, such as chemotherapy, radiation, and hormonal therapy, have become increasingly ineffective because of their severe adverse effects and multidrug resistance. Therefore, the discovery of new potential candidates for BC therapy is essential. Here, we investigated whether ginsenoside Rh1 exhibits anticancer effects on BC. We found that this ginsenoside effectively inhibited the growth of BC cells in both cell cultures and mice. Therefore, ginsenoside Rh1 is a promising candidate for BC treatment.Breast cancer (BC) is the leading cause of cancer-related deaths among women worldwide. Ginsenosides exhibit anticancer activity against various cancer cells. However, the effects of ginsenoside Rh1 on BC and the underlying mechanisms remain unknown. Here, we investigated the anticancer effects of Rh1 on human BC MCF-7 and HCC1428 cells and the underlying signaling pathways. The anticancer effects of Rh1 in vitro were evaluated using sulforhodamine B (SRB), 3-(4, 5-dimethylthiazole-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), clonogenic assay, propidium iodide (PI)/Hoechst staining, Western blotting, flow cytometry, and immunofluorescence analysis. The in vivo effects of Rh1 were determined using a xenograft model via hematoxylin and eosin and the immunohistochemistry staining of tumor tissues. We found that Rh1 exerted cytotoxicity in the cells by increasing cell apoptosis, autophagy, and cell cycle arrest. These effects were further enhanced by a phosphatidylinositol 3-kinase (PI3K) inhibitor but were rescued by the inhibition of reactive oxygen species (ROS). Moreover, enhanced ROS generation by Rh1 inhibited the activation of the PI3K/Akt pathway. Consistently, Rh1 treatment significantly reduced tumor growth in vivo and increased the ROS production and protein expression of LC3B and cleaved caspase-3 but decreased the phosphorylation of Akt and retinoblastoma (Rb) in tumor tissues. Taken together, Rh1 exerted a potential anticancer effect on BC cells by inducing cell cycle arrest, apoptosis, and autophagy via inhibition of the ROS-mediated PI3K/Akt pathway.

Biosynthesis of Silver Nanoparticles by Aspergillus terreus: Characterization, Optimization, and Biological Activities.

In this study, mycelial filtrate of Aspergillus terreus BA6 was used to reduce AgNO3 to form silver nanoparticles (AgNPs). The effect of seven independent variables on the diameter of AgNPs was studied by applying design of experiments (DOE). At optimal conditions, the diameter of AgNPs was reduced by approximately 26.7% compared to the basal culture condition and AgNO3 concentration was found to be the most significant factor affecting the diameter of AgNPs. A. terreus nano-Ag was characterized using UV-visible spectroscopy, transmission electron microscopy, energy dispersive X-ray (EDX), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and Zeta potential. The maximum UV absorption was obtained at 420 nm and the microscopic results showed particles with narrow size distribution ranging from 7 to 23 nm. XRD pattern of AgNPs revealed four diffraction peaks of metallic silver and the EDX spectrum showed a strong signal attributed to Ag nano-crystals. AgNPs mycofabricated by A. terreus showed potent minimum inhibitory concentration (MIC) and broad minimum bactericidal/fungicidal concentration (MBC/MFC) against 12 reference microorganisms. The MIC and MBC/MFC values of AgNPs were 0.312 to 1.25 μg/ml and 0.625 to 10 μg/ml, respectively. Nevertheless, AgNPs did not demonstrate any antagonistic activity against Coxsackie B virus. The in vitro cytotoxicity of the mycosynthesized AgNPs showed significant antitumor activity against adenocarcinoma epithelial cells from human breast cancer (Mcf-7) cell line with an inhibitory concentration (IC50) of 87.5 μg/ml.

Structural, optical, and magnetic properties of nanostructured Ag-substituted Co-Zn ferrites: insights on anticancer and antiproliferative activities

Magnetic spinel ferrite nanoparticles possess high scientific attention for the researchers attributed to its broad area for biomedicine purposes, comprising cancer magnetic hyperthermia and targeted drug delivery. Herein, we report the ultrasound irritation assisted the sol–gel method for the spinel Zn0.5Co0.5-xAg2xFe2O4 (x = 0.00, 0.10, 0.20, and 0.30) nanoparticles (NPs) synthesis. The Rietveld refinement patterns revealed the successful synthesis of the cubic structure Zn0.5Co0.5-xAg2xFe2O4 and the crystallite size ranged from 14.1 nm to 18.4 nm. Also, the optical band gap decreased from 2.39 eV for Co-Zn ferrite to 2.20 eV for Zn0.5Co0.2Ag0.6Fe2O4 sample. Electron paramagnetic resonance spectroscopy was used to study ferromagnetic resonance characteristics of the Zn0.5Co0.5-xAg2xFe2O4 samples. The resonance field was increased from 2512.2 Gauss for Co-Zn ferrite sample to 2834.8 Gauss for Zn0.5Co0.2Ag0.6Fe2O4 sample, while the line width decreased from 2401.3 to 1990.1 Gauss. Also, the saturation was reduced from 45.68 emu.g−1 for the pristine Zn0.5Co0.5Fe2O4 sample to 22.20 emu.g−1 for Zn0.5Co0.2Ag0.6Fe2O4 sample. Furthermore, cytotoxicity of Zn0.5Co0.2Ag0.6Fe2O4 NPs against human breast cancer MCF-7, HepG2 liver cancer, and LoVo colorectal cancer cells was examined. The cytotoxicity of Zn0.5Co0.2Ag0.6Fe2O4 on the previous cancer cell lines resulted in inhibition of cell growth estimated by MTT assay. The exposure of MCF-7, HepG2, and LoVo cancer cells to Zn0.5Co0.2Ag0.6Fe2O4 NPs for 24hs proved a significant apoptotic activity by significant induction of p53 gene expression and caspase activity and antiproliferative activity by amelioration of MMP-2 activity and Bcl-2 gene expression.

Oridonin-Loaded Nanoparticles Inhibit Breast Cancer Progression Through Regulation of ROS-Related Nrf2 Signaling Pathway.

Oridonin (ORI) has been shown to inhibit tumor cell growth and proliferation in vitro, while its optimum anti-tumor activity in vivo is limited due to the poor aqueous solubility and bioavailability. In this study, to improve the bioavailability, we developed a nanoparticle-based drug delivery system to facilitate delivery of ORI to breast tumor. ORI was encapsulated in biodegradable nanoparticles (NPs) based on poly-lactic-co-glycolic acid (PLGA) and polyethylene glycol (PEG) to form ORI NPs (ORI-NPs). The resulting ORI-NPs exhibited a mean particle diameter of 100 nm and displayed an efficient cellular uptake by human breast cancer MCF-7 cells. Compared to free ORI that showed no effects on tumor cell proliferation, the ORI-NPs showed significant cytotoxicity and delayed endothelial cell migration, tube formation and angiogenesis. Pharmacokinetics studies showed that ORI-NPs significantly increased the half-life of ORI in the blood circulation. In the nude mouse xenograft model, ORI-NPs markedly inhibited tumor growth and angiogenesis, while ORI did not show any inhibitory effects on the growth of tumor xenografts. The mechanism experiments showed that the antitumor activity of ORI-NPs against breast cancer might be through ROS related Nrf2/HO-1 signaling pathway. Together, these results demonstrated that ORI-loaded PEG-PLGA NPs enhanced bioactivity and bioavailability in vivo over ORI, indicating that ORI-NPs may represent a promisingly effective candidate against breast cancer.

Evaluation of the Cytotoxic Activity of Biosynthesized Silver Nanoparticles Using Berberis vulgaris Leaf Extract

Background: Recently, due to the numerous applications of silver nanoparticles (AgNPs) in industry, various routes to synthesize them have been developed. Objectives: The current study was aimed at synthesizing silver nanoparticles by the leaf extract of Berberis vulgaris and evaluating the cytotoxic effects on human breast cancer MCF-7 cell line. Methods: The leaf extract of Berberis vulgaris and silver nitrate solution were used to synthesize silver nanoparticles. Ultraviolet (UV)-visible, Fourier-transform infrared, and X-ray diffraction analysis spectroscopy and transmission electron microscopy methods were used to characterize and confirm the nanoparticles’ synthesis. The cytotoxic activity of synthesized nanoparticles (0, 5,10, 20, 40 µg/mL) was also studied by MTT assay. Results: The results showed that Ag nanoparticles were polydisperse and spherical in shape and had a size of about 19.9 nm. Silver nanoparticles reduced the growth of cancerous cells based on time and concentration. The IC50 for MCF-7 cells at 48 hours was 20.27 µg/mL. Conclusions: The findings showed that synthesized nanoparticles have an appropriate cytotoxic effect on cancer cells. This impact may be due to the production of free radicals through the release of Ag ions.

The Differential Selectivity of Aryl Hydrocarbon Receptor (AHR) Agonists towards AHR-Dependent Suppression of Mammosphere Formation and Gene Transcription in Human Breast Cancer Cells.

We had previously reported that treatment with the aryl hydrocarbon receptor (AHR) agonist β-naphthoflavone (βNF) suppressed mammosphere formation derived from cancer stem cells in human breast cancer MCF-7 cells (Cancer Lett., 317, 2012, Zhao et al.). Here, using several AHR agonists, we have investigated the association of this suppression with the classical ability to induce AHR-mediated gene transcription in the xenobiotic response element (XRE). The mammosphere formation assays were performed using wild-type and AHR-knockout MCF-7 cells in the presence of AHR agonists including 3-methylcholanthrene (3MC), benzo[a]pyrene (BaP), 7,12-dimethylbenz[a]anthracene (DMBA), 6-formylindolo[3,2-b]carbazole (FICZ), indirubin, indole-3-carbinol (I3C), indole-3-acetic acid (IAA), and kynurenine (KYN), followed by the XRE-reporter gene assays of the agonists. We showed that treatments with 3MC, BaP, and DMBA strongly suppressed mammosphere formation of the stem cells in an AHR-dependent manner, while other agonists showed weaker suppression. In reporter gene assays, the strength or duration of AHR/XRE-mediated gene transcription was found to be dependent on the agonist. Although strong transcriptional activation was observed with 3MC, FICZ, indirubin, I3C, IAA, or KYN after 6 h of treatment, only weak activation was seen with BaP or DMBA. While transcriptional activation was sustained or increased at 24 h with 3MC, BaP, or DMBA, appreciable reduction was observed with the other agonists. In conclusions, the results demonstrated that the suppressive effects of AHR agonists on mammosphere formation do not necessarily correlate with their abilities to induce AHR-mediated gene transcription. Hence, different AHR functions may be differentially induced in an agonist-dependent manner.

Synergistic Combination of Bioactive Hydroxyapatite Nanoparticles and the Chemotherapeutic Doxorubicin to Overcome Tumor Multidrug Resistance.

Multidrug resistance (MDR) is one of the biggest obstacles in cancer chemotherapy. Here, a remarkable reversal of MDR in breast cancer through the synergistic effects of bioactive hydroxyapatite nanoparticles (HAPNs) and doxorubicin (DOX) is shown. DOX loaded HAPNs (DHAPNs) exhibit a 150-fold reduction in IC50 compared with free DOX for human MDR breast cancer MCF-7/ADR cells, and lead to almost complete inhibition of tumor growth in vivo without obvious side effects of free DOX. This high efficacy and specificity could be attributed to multiple action mechanisms of HAPNs. In addition to acting as the conventional nanocarriers to facilitate the cellular uptake and retention of DOX in MCF-7/ADR cells, more importantly, drug-free HAPNs themselves are able to prevent drug being pumped out of MDR cells through targeting mitochondria to induce mitochondrial damage and inhibit ATP production and to trigger sustained mitochondrial calcium overload and apoptosis in MDR cancer cells while not affecting normal cells. The results demonstrate that this simple but versatile bioactive nanoparticle provides a practical approach to effectively overcome MDR.

Cimicifuga dahurica extract inhibits the proliferation, migration and invasion of breast cancer cells MDA-MB-231 and MCF-7 in vitro and in vivo

Ethnopharmacological relevanceCimicifuga dahurica (Turcz.) Maxim (C. dahurica) has a long history of treating breast cancer. From the Qing Dynasty to the Tang Dynasty and even earlier, C. dahurica has been documented in the treatment of breast carbuncle (Breast cancer is classified as breast carbuncle in Chinese medicine). In traditional prescriptions such as “Sheng Ge Decoction”, “Sheng Ma Powder” and “Breast Carbuncle Pill”, as the main medicine, C. dahurica plays an important role. At present, the systematic studies on the in vitro and in vivo effects of Cimicifuga against breast cancer are rare, especially the C. dahurica. Aim of the studyIn this article, we evaluated the in vitro activity and in vivo effects of CREE (extract of the root of C. dahurica) against breast cancer, and discussed the possible mechanism of CREE in promoting breast cancer cell apoptosis. Materials and methodsThe main component in the CREE was analyzed by HPLC. The effects of CREE on the proliferation, migration and invasion of human breast cancer cells were evaluated through SRB, colony assay, LDH release, wound healing and transwell assay. The pro-apoptotic effect of CREE was investigated in Hochest33342 and Annexin V-FITC/PI assay. To verify the results of CREE in vivo effects, we applied nude mice subcutaneous xenograft experiments. The possible mechanism of CREE treating breast cancer was investigated through mitochondrial membrane potential and western blot experiments. ResultsCREE contains cycloartane triterpene saponins. CREE can significantly inhibit the proliferation, migration and invasion of human breast cancer MCF-7 and MDA-MB-231 cells in vitro and it can effectively inhibit the growth of MDA-MB-231 cell subcutaneous tumors in vivo. Besides, we also found that CREE up-regulated the expression levels of Bax, caspase-9/3 and cytochrome C, and down-regulated the expression of Bcl-2. Therefore, regulation of the mitochondrial pathway may be one of the mechanisms by which CREE promotes breast cancer cell apoptosis. ConclusionsCREE exhibits sufficient anti-breast cancer activity in vivo and in vitro, this study provides persuasive evidence for the further research and development of C. dahurica.