Michigan Cancer Foundation-7 Breast Cancer Cells Research Articles

Anti-metastatic Effect of Heliotropium bacciferum on MCF-7 Human Breast Cancer Cell Line.

Background Heliotropium bacciferum, often known as wild heliotrope or wild quailplant, is a flowering plant from the borage family. This study examines the anti-metastatic impact ofH. bacciferumon Michigan Cancer Foundation-7 (MCF-7) breast cancer cells and its ability to disrupt signaling pathways. Aim To explore the anti-metastatic effect ofH. bacciferumon the MCF-7 breast cancer cell line. Materials and methods For this research, MCF-7 breast cancer cells were used. Cells were cultured and subjected to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, as well as gene expression analysis for glycogen synthase kinase 3 beta (GSK3β), wingless-related integration site 2 (Wnt2), and β-catenin. The plant extract was tested to determine if it successfully blocked the signalling pathway or not. Results The MTT test was performed to study the cytotoxic impact ofH. bacciferum.At an increasing concentration of 100 μg/mL, the extract inhibited growth by 55%, whereas at 150 μg/mL, it inhibited growth by 52.5%. Maximum inhibition was seen at 150 μg/mL.H. bacciferumsuppressed the GSK3β and Wnt2 signaling pathways in MCF-7 breast cancer cell lines, acting as an anti-metastatic and anticancer agent. The heliotrine compound inH. bacciferumshowed high binding energy to metastatic targets such as GSK3β, Wnt2, and β-catenin. Moreover, chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties also support the study. Conclusion In this study, we can infer thatH. bacciferumhas a favourable anticancer impact on MCF-7 breast cancer cell lines and may be utilised as an anticancer drug against breast cancer cells. It can also be further evaluated for different breast cancers and cell lines.

The role of biocompatible coatings of magnetic nanorods on their thermal response in hyperthermia. Consequences on tumor cell survival

There are so many hopes for nanoscience as a tool in the fight against various diseases, notably cancer, that the problem can be approached from many different points of view. In this paper, we focus on two essential aspects. One is the preparation of non-spherical and superparamagnetic magnetic particles, with the right size to be able to exit the blood vessels and be incorporated by cells. The second is their use as agents of hyperthermia. For the first purpose, a two-step method was followed, in which hematite templates with the desired shape and size were first prepared, and these were subsequently reduced by heat treatment. As a result, nanorods with a length of 40 nm and an axis ratio of 1:8 were obtained. The bare particles were coated with a triple layer of cationic/anionic/cationic polymers. Electrophoretic mobility, thermogravimetric analysis, x-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy evaluations confirmed the presence of the coating and the positive charge of the last polymeric layer, while x-ray diffraction and micro-Raman spectroscopy indicated that the crystal structure of the core particles was magnetite/maghemite. The magnetization cycles of the particles showed that they were superparamagnetic, with a saturation magnetization of 82 emu/g in the case of the bare particles. For concentrations up to 300 μg/mL, they were found to be compatible with MCF7 (Michigan Cancer Foundation-7) breast cancer cell line, for cell uptakes higher than 80 %. Both bare and polymer-coated particles produced heating by magnetic hyperthermia and laser-light irradiation. Finally, cytotoxicity against the cancer cells was evaluated, and it was found that photothermia and, above all, magnetic hyperthermia applied to the coated particles could induce more than 50% cell death.

Anti-cancer potential of sea grape (Caulerpa racemosa) extract by altering epithelial-mesenchymal transition and pro-apoptosis proteins expression in MCF-7 breast cancer cells

Breast cancer is a neoplasm that is increasing globally based on its prevalence. Caulerpa racemosa is a type of sea grape that has anti-cancer activity based on previous studies. We aim to determine the anti-cancer activity of C. racemosa extract on Michigan cancer foundation-7 (MCF-7) breast cancer cells through the mechanism of apoptosis by observing cell viability and caspase-3 expression, also as an anti-metastatic agent on expression of Snail and Vimentin. A true experimental study was carried out using a randomized post-test-only control group design. MCF-7 cells were used as subjects with the intervention of C. racemosa extract at varying doses. Cell apoptotic was assessed by flow cytometry and cell viability test, while anti-metastatic activity was assessed by wound healing assay. Immunofluorescence staining was used to assess the expression level of caspase-3, Snail, and Vimentin. The results showed an increased activity of cell apoptosis, according to flow cytometry and cell viability tests. Furthermore, expression of caspase-3 was found to be significantly higher in the 400 g/ml dose group and MCF-7 cell migration inhibition by decreasing Snail and Vimentin protein expression. These results indicate a “novel mechanism” of C. racemosa in the MCF-7 model as an anti-cancer and anti-metastatic agent to inhibit breast cancer progression.

Gold nanoparticles, silver nanoparticles, and silver-gold nanocomposites using Suaeda maritima: Phytochemical analyses, biosynthesis, characterization, and biological activity

Nanoparticles and nanocomposites with low concentration in the body are non-toxic and can be suitable alternative to antibiotics. Gold nanoparticles (AuNPs), silver nanoparticles (AgNPs), and silver-gold nanocomposite (Ag-Au NCs) were synthesized for the first time using galangin (GA) from Suaeda maritima (SM). A simple method was studied and optimized for the biosynthesis of AuNPs, AgNPs, and Ag-Au NCs using GA of SM. A variety of phytochemical compounds found in SM, such as phenols, convert metal into ions and serve as capping agents. The SM phytochemical analysis indicates a high concentration of GA in leaf shell extract, which is a flavonoid with anti-tumor properties. Characterization of GASMAuNPs, GASMAgNPs, and GASMAg-Au NCs was performed using a variety of spectroscopy and microscopy techniques. Based on transmission electron microscopy and field emission scanning electron microscopy, the size of the GASM-Ag-AuNCs (45 nm), GASM-AgNPs (50 nm) and GASM-AuNPs (7 nm) and was spherical. The cytotoxicity effects of these nanoparticles and nanocomposites on Michigan Cancer Foundation-7 (MCF-7) breast cancer cell lines were studied. GA-SM-Ag-AuNCs reduced the cell viability of MCF-7 breast cancer cell lines. Antibacterial activities were evaluated against Staphylococcus aureus, Klebsiella pneumoniae, Proteus mirabilis, and Escherichia coli. GA-SM-Ag-Au NCs had maximum inhibition zones for Escherichia coli and Staphylococcus aureus. The maximum inhibition zones observed with GA-SM-Ag-AuNCs were higher than clindamycin, gentamycin, and tetracycline. The minimum inhibitory concentration (MIC) of GA-SM-Ag-AuNCs against Escherichia coli and Staphylococcus aureus was 15.6 μgmL−1. GA-SM-Ag-AuNCs have powerful antimicrobial potential, while having less cytotoxicity at low concentrations. The GA-SM-Ag-AuNCs reduced the cytotoxicity effects on MCF-7. This study showed that GASM-Ag-AuNCs synthesized using GA of SM has antibacterial and anticancer properties with fewer side effects and significant efficacy, which can be effective as a potential therapy in the future.

Nociceptin/Orphanin FQ receptor expression in primary human umbilical vein endothelial cells is not regulated by exposure to breast cancer cell media or angiogenic stimuli.

Opioid receptors are naloxone-sensitive (MOP [mu: μ], DOP [delta: δ], and KOP [kappa: κ]) and naloxone-insensitive Nociceptin/Orphanin FQ (N/OFQ) peptide receptor (NOP). Clinically, most opioid analgesics target MOP. Angiogenesis is the formation of new blood vessels and involves endothelial cell activation, proliferation, and migration. The effect of opioids on this process is controversial with no data for NOP receptor ligands. We used patient-derived human umbilical vein endothelial cells (HUVECs) treated with media from the Michigan Cancer Foundation-7 (MCF-7) breast cancer cells or vascular endothelial growth factor (VEGF; 10 ng ml-1) and fibroblast growth factor (FGF; 10 ng ml-1) as angiogenic stimuli. We have measured (i) NOP/MOP messenger RNA, (ii) receptor protein using N/OFQATTO594 and DermorphinATTO488 as fluorescent probes for NOP and MOP, and (iii) NOP/MOP function in a wound healing assay (crude measure of migration that occurs during angiogenesis). HUVEC lines from 32 patients were used. Using all 32 lines, mRNA for NOP but not MOP was detected. This was unaffected by media from MCF-7 cells or VEGF/FGF. There was no binding of either N/OFQATTO594(NOP) or DermorphinATTO488(MOP) in the absence or presence of angiogenic stimuli (six lines tested). In the absence of MOP mRNA, this was expected. Whilst MCF-7 conditioned medium (not VEGF/FGF) reduced wound healing per se (14 lines tested), there was no effect of N/OFQ (NOP ligand) or morphine (MOP ligand). Media from MCF-7 breast cancer cells or VEGF/FGF as angiogenic stimuli did not influence NOP translation into receptor protein. MOP was absent. In the absence of constitutive or inducible MOP/NOP, there was no effect on wound healing as a measure of angiogenesis.

Evaluation of the Cytotoxic Effects of Concomitant Use of Ag/ZnO Nanoparticles and Curcumin on MCF7 Breast Cancer Cell Line

Introduction: Cancer is the second cause of death. The use of a new drug delivery system that can deliver the drug to the tumor site and prevent it from entering the body's natural tissues is essential. Metal oxide nanoparticles have been considered one of the effective candidates for cancer treatment. For this reason, our study was conducted to investigate the cytotoxic effect of the simultaneous use of Ag/ZnO nanoparticles and curcumin on the Michigan Cancer Foundation-7 (MCF7) breast cancer cell line. Method: The MTT colorimetric method was used to investigate the synergistic effects of zinc oxide silver nanoparticles and curcumin. Cells with different concentrations of zinc oxide silver nanoparticles and curcumin, including 3.9, 7.8, 15.62, 31.25, 62.5, 125, 250, 500, and 1000 micrograms/ml during 24 and 48 h were incubated in triplicate to observe the synergistic effects of each of these concentrations, ratios of 1 to 1, 0.5 to 0.5, 0.25 to 0.75 of zinc oxide silver nanoparticles and curcumin were used. The viability of the cells treated with the drug was determined in the form of the percentage of light absorption of the produced formazan and was shown in a two-dimensional curve. Results: The effect of Ag/ZnO nanoparticles alone on the survival rate of cancer cells had a significant difference with curcumin. In addition, in the simultaneous examination of Ag/ZnO nanoparticles and curcumin, much more cytotoxicity was observed than in Ag/ZnO alone. Conclusion: In general, the simultaneous use of chemotherapy drugs and nanoparticles can decrease the concentration of chemotherapy drugs used in cancer treatment.

Combination of Antimalarial and CNS Drugs with Antineoplastic Agents in MCF-7 Breast and HT-29 Colon Cancer Cells: Biosafety Evaluation and Mechanism of Action.

Drug combination and drug repurposing are two strategies that allow to find novel oncological therapies, in a faster and more economical process. In our previous studies, we developed a novel model of drug combination using antineoplastic and different repurposed drugs. We demonstrated the combinations of doxorubicin (DOX) + artesunate, DOX + chloroquine, paclitaxel (PTX) + fluoxetine, PTX + fluphenazine, and PTX + benztropine induce significant cytotoxicity in Michigan Cancer Foundation-7 (MCF-7) breast cancer cells. Furthermore, it was found that 5-FU + thioridazine and 5-fluorouracil (5-FU) + sertraline can synergistically induce a reduction in the viability of human colorectal adenocarcinoma cell line (HT-29). In this study, we aim to (1) evaluate the biosafety profile of these drug combinations for non-tumoral cells and (2) determine their mechanism of action in cancer cells. To do so, human fetal lung fibroblast cells (MRC-5) fibroblast cells were incubated for 48 h with all drugs, alone and in combination in concentrations of 0.25, 0.5, 1, 2, and 4 times their half-maximal inhibitory concentration (IC50). Cell morphology and viability were evaluated. Next, we designed and constructed a cell microarray to perform immunohistochemistry studies for the evaluation of palmitoyl-protein thioesterase 1 (PPT1), Ki67, cleaved-poly (ADP-ribose) polymerase (cleaved-PARP), multidrug resistance-associated protein 2 (MRP2), P-glycoprotein (P-gp), and nuclear factor-kappa-B (NF-kB) p65 expression. We demonstrate that these combinations are cytotoxic for cancer cells and safe for non-tumoral cells at lower concentrations. Furthermore, it is also demonstrated that PPT1 may have an important role in the mechanism of action of these combinations, as demonstrated by their ability to decrease PPT1 expression. These results support the use of antimalarial and central nervous system (CNS) drugs in combination regimens with chemotherapeutic agents; nevertheless, additional studies are recommended to further explore their complete mechanisms of action.

A modular, reversible sealing, and reusable microfluidic device for drug screening

Preclinical tests for evaluating potential drug candidates using conventional protocols can be exhaustive and high-cost processes. Microfluidic technologies that can speed up this process and allow fast screening of drugs are promising alternatives. This work presents the design, concept, and operational conditions of a simple, modular, and reversible sealing microdevice useful for drug screening. This microdevice allows for the operation of 4 parallel simultaneous conditions and can also generate a diffusive concentration gradient in sextuplicates. We used laminated polydimethylsiloxane (PDMSLAM) and glass as building materials as proof of concept. The PDMSLAM parts can be reused since they can be easily sterilized. We cultured MCF-7 (Michigan Cancer Foundation-7) breast cancer cells. Cells were exposed to a doxorubicin diffusive concentration gradient for 3 h. They were monitored by automated microscopy, and after data processing, it was possible to determine cell viability as a function of doxorubicin concentration. The reversible sealing enabled the recovery of the tested cells and image acquisition. Therefore, this microdevice is a promising tool for drug screening that allows assessing the cellular behavior in dynamic conditions and the recovery of cells for afterward processing and imaging.

Amelioration of Tumor Targeting andIn VivoBiodistribution of99mTc-Methotrexate-Gold Nanoparticles (99mTc-Mex-AuNPs).

Gold nanoparticles (AuNPs) represent very attractive and promising drug delivery carriers due to their unique dimensions, adjustable surface functions, and controllable drug release. Therefore, AuNPs are used to overcome the limitations of conventional chemotherapy, for example methotrexate (Mex), one of the first-generation chemotherapy drugs for cancer treatment, whose usefulness has been restricted due to drug resistance and dose-dependent side effects. In the present study, the AuNPs drug delivery system was synthesized and loaded with technetium-99m radiolabeled Methotrexate (99mTc-Mex) to produce new potential nanoradiopharmaceutical for tumor targeting and further imaging. The Methotrexate loaded gold nanoparticles (Mex-AuNPs) successfully prepared in small spherical particle size (20.3nm), polydispersity index PDI (< 0.5) and a zeta potential (-17.6mV) with loading efficiency% (93±1.2%) of methotrexate at 30min as an optimum stirring time and showed strong absorption peak for Mex-AuNPs at λmax, 525nm. The in vitro release profile of Mex-AuNPs showed high release percent of methotrexate at pH 5; the Q0.5h and Q8h were 21.2±1.5% and 92.9±3.4%, respectively. The in vitro cytotoxicity was investigated at different concentrations (0.024-50 μl/100 μl) of Mex-AuNPs (1mg/ml) against MCF-7 (Michigan Cancer Foundation-7) breast cancer cells by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay technique. Mex-AuNPs showed higher anticancer activity with low inhibitory concentration (IC50=0.098 μl/100 μl) that was three times lower than the inhibitory concentration (IC50) of methotrexate (IC50=0.3 μl/100 μl). 99mTc-Mex complex prepared by direct reduction method at maximum radiochemical yield (RCY)% ̴ 98.3±1.09% was loaded in AuNPs to form 99mTc-Mex-AuNPs with loading efficiency% (93±1.2%) at 30min of stirring time. 99mTc-Mex-AuNPs showed convenient in vitro stability in mice serum up to 24h with RCY% > 90%. The preclinical biodistribution studies of 99mTc-Mex-AuNPs were performed in 3 experimental groups A (intravenous (I.V.) injected normal mice), B and C (I.V. and intratumor (I.T.) injected tumor bearing mice, respectively). The 99mTc-Mex-AuNPs achieved highest tumor uptake (93±0.39%ID/g) and highest Target/NonTarget (T/NT) ratio (58.1±0.91) with high Tumor/Blood (T/B) ratio (25.8±0.11) at 10min post I.T. injection and retained high tumor uptake (79±0.65%ID/g) up to 60min post I.T. injection before escaping into blood stream. Consequently, 99mTc-Mex-AuNPs can be considered as new potential nanoradiopharmaceutical in tumor diagnosis.

The Efficacy of siRNA Specific MDM2 in the Induction of Apoptosis in MCF-7 Breast Cancer Cell Line

Background: A high number of human breast cancers overexpress the murine double minute (MDM2) gene which blocks the p53 protein which plays an important role in arresting the cell growth. The present study aimed to investigate the efficacy of siRNA specific MDM2 in knocking down MDM2 and its subsequent effects on p53 to exert antiproliferative effects on Michigan Cancer Foundation-7 (MCF-7) breast cancer cells. Method: In this in vitro study, we used the specific siRNA of the MDM2 gene to knock down the expression of the MDM2 protein in the MCF-7 cell line. The expression of MDM2, BCL2-associated X (BAX), BH3 interacting-domain death agonist (BID), and B cell lymphoma 2 (BCL2) genes was evaluated using the Real-time PCR technique. The apoptosis level was also assessed using the flow cytometry technique by the Annexin V test. Results: The results showed that the entry of MDM2 siRNA into MCF-7 cells significantly reduced the mRNA expression of MDM2 gene (P-value <0.05). Besides, the expression of the anti-apoptotic gene of BCL2 significantly decreased (P-value <0.05) in transfected MCF-7 cells, while that of BAX and BID genes increased (P-value <0.05). Conclusion: Based on the results, MDM2 inhibition is conducive to prevent cancer metastasis by the induction of cancer cell apoptosis. Moreover, it can be considered in cancer therapy along with chemotherapy.

Green-Synthesized Silver Nanoparticles Induced Apoptotic Cell Death in MCF-7 Breast Cancer Cells by Generating Reactive Oxygen Species and Activating Caspase 3 and 9 Enzyme Activities.

Silver nanoparticles are among the most significant diagnostic and therapeutic agents in the field of nanomedicines. In the current study, the green chemistry approach was made to optimize a cost-effective synthesis protocol for silver nanoparticles from the aqueous extract of the important anticancer plant Fagonia indica. We investigated the anticancer potential and possible involvement of AgNPs in apoptosis. The biosynthesized AgNPs are stable (zeta potential, -16.3 mV) and spherical with a crystal size range from 10 to 60 nm. The MTT cell viability assay shows concentration-dependent inhibition of the growth of Michigan Cancer Foundation-7 (MCF-7) cells (IC50, 12.35 μg/mL). In addition, the fluorescent microscopic analysis shows activation of caspases 3 and 9 by AgNPs that cause morphological changes (AO/EB assay) in the cell membrane and cause nuclear condensation (DAPI assay) that eventually lead to apoptotic cell death (Annexin V/PI assay). It was also observed that AgNPs generate reactive oxygen species (ROS) that modulate oxidative stress in MCF-7 cells. This is the first study that reports the synthesis of a silver nanoparticle mediated by Fagonia indica extract and evaluation of the cellular and molecular mechanism of apoptosis.

Synthesis of lactoferrin mesoporous silica nanoparticles for pemetrexed/ellagic acid synergistic breast cancer therapy

Despite the clinical approval of few nanomedicines for cancer therapy, some drawbacks still impede their improved efficiency including low drug loading, off-target toxicity and development of multi-drug resistance. Herein, lactoferrin (Lf)-coupled mesoporous silica nanoparticles (MSNPs) were developed for combined delivery of the cytotoxic drug pemetrexed (PMT) and the phytomedicine ellagic acid (EA) for synergistic breast cancer therapy. While the hydrophobic EA was physically encapsulated within the pores of MSNPs via the adsorptive properties of MSNPs and the electrostatic interactions between the negatively charged EA and positively charged amino modified MSNs, the highly water soluble PMT was chemically anchored to the Lf shell through chemical conjugation to the surface of lactoferrin coated MSNPs by carbodiimide reaction to avoid pre-mature drug release and systemic toxicity. The dual drug-loaded Lf-MSNPs (284 nm) demonstrated a sequential faster release of EA followed by a sustained release of PMT. The dual drug-loaded Lf-MSNPs exhibited highest cytotoxicity against MCF-7 (Michigan Cancer Foundation-7) breast cancer cells as revealed by the lowest combination index (CI = 0.885) compared to free drugs. The combination index value (< 1) revealed synergy between both loaded drugs. Furthermore, high cellular uptake of the nanocarriers into MCF-7 breast cancer cells was observed via Lf-receptor mediated endocytosis. Altogether, the dual drug-loaded Lf-targeted MSNPs showed to be a promising carrier for breast cancer therapy through triggering different signaling pathways, and hence overcoming the multi-drug resistance and minimizing the systemic toxicity.

Increased expression of the HDAC9 gene is associated with antiestrogen resistance of breast cancers.

Estrogens play a pivotal role in breast cancer etiology, and endocrine therapy remains the main first line treatment for estrogen receptor‐alpha (ERα)‐positive breast cancer. ER are transcription factors whose activity is finely regulated by various regulatory complexes, including histone deacetylases (HDACs). Here, we investigated the role of HDAC9 in ERα signaling and response to antiestrogens in breast cancer cells. Various Michigan Cancer Foundation‐7 (MCF7) breast cancer cell lines that overexpress class IIa HDAC9 or that are resistant to the partial antiestrogen 4‐hydroxy‐tamoxifen (OHTam) were used to study phenotypic changes in response to ER ligands by using transcriptomic and gene set enrichment analyses. Kaplan–Meier survival analyses were performed using public transcriptomic datasets from human breast cancer biopsies. In MCF7 breast cancer cells, HDAC9 decreased ERα mRNA and protein expression and inhibited its transcriptional activity. Conversely, HDAC9 mRNA was strongly overexpressed in OHTam‐resistant MCF7 cells and in ERα‐negative breast tumor cell lines. Moreover, HDAC9‐overexpressing cells were less sensitive to OHTam antiproliferative effects compared with parental MCF7 cells. Several genes (including MUC1, SMC3 and S100P) were similarly deregulated in OHTam‐resistant and in HDAC9‐overexpressing MCF7 cells. Finally, HDAC9 expression was positively associated with genes upregulated in endocrine therapy‐resistant breast cancers and high HDAC9 levels were associated with worse prognosis in patients treated with OHTam. These results demonstrate the complex interactions of class IIa HDAC9 with ERα signaling in breast cancer cells and its effect on the response to hormone therapy.

Avoiding the Interference of Doxorubicin with MTT Measurements on the MCF-7 Breast Cancer Cell Line.

Doxorubicin (DOXO) is an adjuvant chemotherapy agent and is also commonly used in cell biology research. Cytotoxic assays in cell culture are frequently used in order to stablish drug concentrations that are useful for controlling cell proliferation. One common cytotoxic method used is 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT). Our present research aims to support future studies in engaging MTT assay using DOXO that exhibits a strong red coloration and fluorescence, and so it is assumed that DOXO may interfere with commonly used colorimetric assays such as MTT. The interference of DOXO in the MTT determination was evaluated in a Breast Cancer cell line Michigan Cancer Foundation-7 (MCF-7). The interference was evaluated by means of spectroscopic methods in particular spectrophometry and fluorescence spectroscopy of MTT and DOXO. We postulate that the medium and the MTT reagent itself can interfere on the metabolic activity method, so in order to achieve better results, DMEM was replaced by a neutral buffer like Phosphate-buffered saline (PBS). This protocol may be extremely useful in future studies involving DOXO.

DESIGN, SYNTHESIS, MOLECULAR DOCKING, AND BIOLOGICAL EVALUATION OF PYRAZOLE 1-CARBOTHIAMIDE INCORPORATED ISOXAZOLE DERIVATIVES

Objectives: Novel isoxazole incorporated pyrazole carbothiamide 5 (a-r) was designed and synthesized, docked and evaluated for anticancer activity Michigan Cancer Foundation-7 (MCF-7), and breast cancer cell lines.&#x0D; Materials and Methods: Designed compounds were synthesized by the condensation of 1-(5-methyl-3-(4-nitrophenyl) isoxazole-4-yl) -3-(substitutedphenyl) prop-2-en-1-one (4) with thiosemicarbazides and substituted thiosemicarbazides to give the target molecules 5 (a-r). To predict the affinity and activity of the ligand molecule, the docking program Accelrys Discovery Studio 2.1 was employed to generate different bioactive binding poses of designing molecules at the active site of human Dihydrofolate Reductase (DHFR) (PDB ID: 1KMS). All the synthesized compounds were characterized based on the spectral and elemental analysis data. Antiproliferative activity was performed against MCF-7 breast cancer cell lines.&#x0D; Results: All the synthesized compounds showed the characteristic peaks in Fourier-transform infrared,1H C13NMR, and mass spectral analysis. During docking, all the synthesized compounds 5 (a-r) exhibited higher fitness scores with minimum three bonding interaction with the active site human DHFR (PDB ID: 1KMS). In the MTT assay based on MCF-7 breast cancer cell lines, most of the compounds exhibited significant activity. In the antiproliferative assay against MCF-7 cell lines, most of the compounds exhibited potent activity with IC50 values in micromolar concentrations. Compounds 5a, 5b, 5f, 5h, and 5k have exhibited significant anticancer activity.&#x0D; Conclusions: The derivatives were synthesized in quantitative yields. New derivatives possess the antiproliferative activity and antitubercular activity.

Inhibitory Effects of Silica Nanoparticles Loaded with Hematoporphyrin on Breast Cancer Cell Line

Background: Cancer is one of the main causes of death in the world. In recent years, many studies have been conducted on the usage of nanomaterials in cancer treatment. In previous studies, the anti-tumor effects of mesoporous silica nanoparticles (MSN) on cancer cells have been shown. The aim of this study was to evaluate the effect of MSN loaded with Hematoporphyrin (HpD) on the cell proliferation and invasion of MCF7 (Michigan Cancer Foundation-7) breast cancer cell line. The antioxidant effects of MSN loaded with HpD were also investigated. Methods: In this study, using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, the proliferation and viability of cancer cells were studied after exposure to MSN loaded with HpD. The wound healing assay technique (migration test) was used for the assessment of cancer cells’ invasion. The antioxidant effects of MSN loaded with HpD were studied by DPPH (2,2-diphenyl-1-picrylhydrazyl) assay and FRAP (ferric reducing/antioxidant power) assay techniques. Results: Our results showed that the viability and proliferation of breast cancer cell line MCF7 in the presence of silica nanoparticles loaded with hematoporphyrin (HpD) significantly declined (P = 0.02). After exposure to mesoporous silica nanoparticles (MSN) loaded with hematoporphyrin (HpD), the cancer cell invasion decreased (P = 0.025). Silica nanoparticles alone and loaded with hematoporphyrin (HpD) showed considerable cytotoxic activities against cancer cell lines (IC50 = 20 - 30 μg.mL-1). The most promising result was achieved for MSN loaded with hematoporphyrin (HpD) with the minimum IC50 value. It was found that the proliferation rate of MCF7 cells decreased after treatment with this compound in a dose-dependent manner. The assessments with DPPH assay and FRAP assay techniques showed that MSN and MSN loaded with HpD have antioxidant activities. Conclusions: MSN loaded with HpD have an inhibitory effect on the growth of the MCF7 cell line. MSN alone and in combination with HpD have an inhibitory effect on cell invasion in the MCF7 cell line. MSN alone and loaded with HpD have antioxidant effects. These results indicate that MSN has the potential to be used in cancer treatment as a carrier for anticancer drugs. Keywords: Silica Nanoparticles; Hematoporphyrin; Cell Viability; Invasion; Antioxidant; Breast Cancer; Cell Line

IN-VITRO CYTOTOXIC AND APOPTOSIS STUDY OF CHEMICAL CONSTITUENTS OF CLERODENDRUM PHLOMIDIS LEAF ON MCF-7 BREAST AND A-549 LUNG CANCER CELL LINES.

Objective: Cancer is a molecularly heterogeneous diseaseand the leading cause of death worldwide. The methanol extract of Clerodendrum phlomidis leaf has been reported for cytotoxicity. Hence, the current investigation was planned to evaluate the cytotoxic activity of the chemical constituents isolated from the methanol extract of the C. phlomidis leaf against the Michigan cancer foundation-7 (MCF-7) breast cancer and adenocarcinomic human alveolar basal epithelial cells (A549) lung cancer cell lines by the apoptotic study.Methods: Cytotoxic activity of the chemical constituents of the methanol extract of the C. phlomidis leaf was evaluated by the 3-(4,5-dimethylthiazol- 2-yl)-5-diphenyltetrazolium bromide (MTT) assay against breast cancer (MCF-7) and lung cancer (A549) cell lines. The MCF-7 and A549 cell lines were tested at different concentrations to determine 50% of growth inhibition (inhibitory concentration [IC50]) by MTT assay. Apoptosis of nuclei was detected by 4’,6-diamidino-2-phenylindole staining assay.Results: In MCF-7 breast cancer cell line study, Compounds 6 and 9 exhibited good cytotoxic activity with an IC50 value of 83.80 and 75.16 μg/ml, respectively. In A549 lung cancer cell line, again Compounds 6 and 9 exhibited good cytotoxic activity with an IC50 value of 84.46 and 78.60 μg/ml, respectively. Percentage of apoptosis induced by the Compounds 6 and 9 in the MCF-7 cancer cells was found to be 74.50 and 85.48, respectively.Conclusion: The results of the current study prove that the Compounds 6 and 9 are potential agents for breast and lung cancer. In future research, these potential agents can further be evaluated by animal studies and their mechanism of action apart from the induction of apoptosis of the cancer cells can be determined.

Flavone constituents of Phlomis bruguieri Desf. with cytotoxic activity against MCF-7 breast cancer cells.

Phlomis bruguieri (P. bruguieri) is a large genus in the Lamiaceae family, with a wide variety distributed in Euro-Asia, Central Asia, Iran, and China. Phlomis flowers have been used as herbal tea for gastrointestinal disturbances, protection of liver and cardiovascular systems. The aim of this study was to analyse phytochemical of flavonoid constituents in semi polar fraction of P. bruguieri. Methanol extract of plant material (4 kg) yielded 361 g dark green concentrated extract gum. After preliminary fractionation by normal column chromatography on silica gel, Fr. 2 eluted with chloroform: methanol (90:10) selected as semi polar fraction and was more purified using different chromatography columns on silica gel, polyamide SC6 and Sephadex LH-20 adsorbents. Finally one new and three known flavonoids (1-4) were characterized in semi polar fraction. Isolated structures were identified using 1H-NMR, 13C-NMR, 31P-NMR, HSQC, HMBC, negative ESI mass, and UV spectra using different shift reagents. Using standard MTT assay, cytotoxicity of isolated new compound was done against michigan cancer foundation-7 (MCF-7) breast cancer cells. Phytochemical analysis of P. bruguieri resulted in identification of one new 4’-methoxy-luteolin-7-phosphate and three known flavones including luteolin, apigenin, and tricin for the first time in this plant. In MTT cytotoxicity test, 4’-methoxy-luteolin-7-phosphate showed cytotoxicity with IC50 value of 43.65 ± 8.56 μM agasint MCF-7 breast cancer cells.

Structure-based pharmacophore design and virtual screening for novel potential inhibitors of epidermal growth factor receptor as an approach to breast cancer chemotherapy.

Cancer cells are described with features of uncontrolled growth, invasion and metastasis. The epidermal growth factor receptor subfamily of tyrosine kinases (EGFR-TK) plays a crucial regulatory role in the control of cellular proliferation and progression of various cancers. Therefore, its inhibition might lead to the discovery of a new generation of anticancer drugs. In the present study, structure-based pharmacophore modeling, molecular docking and molecular dynamics simulations were applied to identify potential hits, which exhibited good inhibition on the proliferation of MCF-7 breast cancer cell line and favorable binding interactions on EGFR-TK. Selected compounds were examined for their anticancer activity against the Michigan Cancer Foundation-7 (MCF-7) breast cancer cell line which overexpresses EGFR using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay. Compounds 1 and 2, with an isoindoline-1-one core, induced significant inhibition of breast cancer cells proliferation with IC[Formula: see text] values 327 and 370 nM, respectively.

RAFT Polymerization for the Synthesis of Tertiary Amine-Based Diblock Copolymer Nucleic Acid Delivery Vehicles.

The synthesis and characterization of a family of nine pH-responsive, diblock copolymers designed to effectively deliver nucleic acids are reported. The stabilizing A block is comprised of an oligo(ethylene glycol) methyl ether methacrylate to impart water solubility. The cationic blocks of varying degrees of polymerization (DPs) are derived from three pH responsive, tertiary amine-containing methacrylates capable of complexing negatively charged nucleic acids. The cytotoxicity studies utilizing human embryonic kidney cells (HEK-293) and Michigan Cancer Foundation-7 (MCF-7) breast cancer cells indicate no decrease of cell viability with the diblock copolymers, with the exception of the two highest DPs of the cationic blocks with ethyl-substitutes tertiary amine. Gene knockdown experiments indicate high siRNA delivery and MYC gene knockdown in MCF-7 breast cancer cells for eight of the nine studied block copolymers. The results of the current study enable further development of the pH-responsive copolymer family for promising nucleic acid delivery vehicles applicable for clinical use.