Breast Carcinoma Cell Line MCF-7 Research Articles

Absence of herb-drug interactions of mistletoe with the tamoxifen metabolite (E/Z)-endoxifen and cytochrome P450 3A4/5 and 2D6 in vitro

Women diagnosed with breast cancer frequently seek complementary and alternative (CAM) treatment options that can help to cope with their disease and the side effects of conventional cancer therapy. Especially in Europe, breast cancer patients use herbal products containing mistletoe (Viscum album L.). The oldest and one of the most prescribed conventional drugs for the treatment of estrogen receptor positive breast cancer is tamoxifen. Aside from positive clinical experience with the combination of tamoxifen and mistletoe, little is known about possible herb-drug interactions (HDIs) between the two products. In the present in vitro study, we investigated the effect of standardized commercial mistletoe preparations on the activity of endoxifen, the major active metabolite of tamoxifen. The estrogen receptor positive human breast carcinoma cell line MCF-7 was treated with (E/Z)-endoxifen hydrochloride in the presence and absence of a defined estradiol concentration. Each concentration of the drug was combined with fermented Viscum album L. extracts (VAE) at clinically relevant doses, and proliferation, apoptosis and cell cycle were analyzed. In parallel, possible inhibition of CYP3A4/5 and CYP2D6 was investigated using 50-donor mixed gender pooled human liver microsomes (HLMs). VAE did not inhibit endoxifen induced cytostasis and cytotoxicity. At higher concentrations, VAE showed an additive inhibitory effect. VAE preparations did not cause inhibition of CYP3A4/5 and CYP2D6 catalyzed tamoxifen metabolism. The in vitro results suggest that mistletoe preparations can be used in combination with tamoxifen without the risk of HDIs.

Hypomethylation of mismatch repair genes MLH1 and MSH2 is associated with chemotolerance of breast carcinoma: Clinical significance.

The aim of the study was to understand the importance of mismatch repair genes MLH1 and MSH2 in chemotolerance and prognosis of breast carcinoma (BC). First, the alterations (deletion/methylation/expression) of MLH1 and MSH2 were analyzed in 45 neoadjuvant chemotherapy (NACT)-treated and 133 pretherapeutic BC samples. The chemotolerant BC cells were characterized by treating two BC cell lines MCF-7 and MDA MB 231 with two anthracycline antitumor antibiotics, doxorubicin and nogalamycin. The deletion frequencies were 32% to 38% in MLH1/MSH2 genes and promoter methylation frequencies were 49% to 62% in MLH1 and 41% to 51% in MSH2 in both NACT-treated and pretherapeutic samples. The overall alteration of MLH1 and MSH2 was 58% to 71% in the samples. Reduced messenger RNA (mRNA) and protein expression were found in both the genes and it showed concordance with the molecular alterations. NACT-treated patients showed better prognosis. The chemotherapeutic drug induced increased mRNA/protein expression of the genes in BC cell lines was due to their promoter hypomethylation, as analyzed by quantitative methylation assay. This phenomenon was also evident in NACT-treated BC samples. MLH1/MSH2 genes play a critical role in the development of BC. Hypomethylation of MLH1/MSH2 genes might be important in chemotolerance of the disease.

Study of the anti(myco)bacterial and antitumor activities of prolinate and N-amidocarbothiolprolinate derivatives based on fused tetrahydropyrrolo[3,4-c]pyrrole-1,3(2H,3aH)-dione, bearing an indole ring

A series of prolinate and N-amidocarbothiolprolinate derivatives based on a fused pyrrole-3,4-dione core, bearing indole ring systems, are prepared from the corresponding amino acid and an aldehyde via thermal 1,3-dipolar cycloaddition of azomethine ylides and condensation with benzoylisothiocyanate. Products are fully characterized by NMR, FT-IR, MS, and an X-ray crystal structure. The prepared compounds are screened for their antibacterial activity against a range of Gram-positive and Gram-negative bacteria and their antimycobacterial activity against M. tuberculosis H37Rv strain. In addition, two selected target compounds are evaluated for cytotoxicity, apoptosis, and anti-inflammatory effects on MCF-7 (breast carcinoma) cell lines. The incorporation of indole ring and –C(O)NHC(S)– moiety resulted to be beneficial since the biological point of view.

Butea monosperma (Lam.) Taub. Bark fractions protect against free radicals and induce apoptosis in MCF-7 breast cancer cells via cell-cycle arrest and ROS-mediated pathway

Butea monosperma (Lam.) Taub. is an ethnomedicinal tree of remedial value in the treatment of diabetes, bone fractures, and liver and neurological disorders. However, the information available on DNA-protective and anti-proliferative potential of bark of this tree is scarce. In the present study, the extract/fractions obtained from bark of B. monosperma were evaluated for antioxidant, DNA-protective, and anti-proliferative activities, along with their phytochemical profiling for identifying major constituents present in them. Different extract/fractions, namely, Bmth (methanol), Bhex (hexane), Bchl (chloroform), and Beac (ethyl acetate), were prepared and evaluated for antioxidant activity using in vitro assays. Extract/fractions were also evaluated for anti-proliferative and apoptotic activity in human breast carcinoma cell line MCF-7, using in vitro assays, namely, MTT, clonogenic, and neutral comet assay, along with confocal microscopy and flow cytometry. Among all extract/fractions, a pronounced antioxidant activity was exhibited by Bchl and Beac fractions, in DPPH· (EC50 213.2 and 161.5 µg/mL, respectively), ABTS+ · (EC50 139.3 and 44.1 µg/mL, respectively), and reducing power assay (EC50 86.7 and 84.5 µg/mL, respectively). Both fractions protected plasmid DNA against hydroxyl radical induced damage in plasmid nicking assay. Bchl and Beac were also observed to inhibit the growth of MCF-7 cells (GI50 203.7 and 246.5 µg/mL, respectively). Both fractions induced apoptosis in MCF-7 cells, by arresting the cell cycle in G1 and sub-G1 phase, respectively, enhancing ROS levels, decreasing mitochondrial membrane potential, and inducing double-strand DNA breaks. HPLC analysis revealed high kaempferol content in Bchl, and catechin, epicatechin, and gallic acid in Beac.

Further insights into ruthenium(II) piano-stool complexes with N-alkyl imidazoles

Two piano-stool ruthenium(II) complexes [Ru(η6-p-cymene)(N-MeIm)3]Cl2·2H2O (1) and [Ru(η6-p-cymene)(N-PrIm)Cl2] (2) respectively have been synthesized and characterized by elemental, spectral and structural analysis. Crystal structures of (1) and (2) have been verified by X-ray diffraction analysis. Docking experiments toward DNA dodecamer have been done. Good ΔG binding values of the complexes with imidazole derivatives comparable with ethylene-diamine complex indicate a high potential of these compounds in the formation of DNA lesions and therefore their good cytotoxic status. The interaction of CT-DNA with ruthenium(II) complexes has been studied by means of absorption and fluorescence measurements. The binding constant, Kb and the Stern–Volmer quenching constant reveal that complex (2) binds well to CT-DNA. The cytotoxic activity of Ru(II) complexes with N-RIm (R = methyl or propyl) were evaluated by MTT assay. A-549, HT-29 and HeLa cells were sensitive to all compounds tested, while the breast carcinoma cell line MCF-7 was resistant only to the complex (1). Flow cytometric analysis and fluorescent microscopy showed that ruthenium(II) complexes in HeLa cells induce apoptosis and G0/G1 cell cycle arrest and almost completely inhibit DNA synthesis. Western blot also demonstrated proteolytic cleavage of poly-(ADP-ribose) polymerase (PARP) in HeLa cells after treatment with both tested substances.

α-Aroylketene Dithioacetal Mediated Synthesis of (E)-3-(benzo[d]thiazol-2-ylamino)-2-(1-methyl-1H-indole-3-carbonyl)-3-(methylthio)acrylonitrile Derivatives and their Biological Evaluation.

The blending of two pharmacophores would generate novel molecular templates that are likely to exhibit interesting biological properties. A facile, efficient and high yielding synthesis of (E)-3-(benzo[d]thiazol-2-ylamino)-2-(1-methyl-1Hindole- 3-carbonyl)-3-(methylthio) acrylonitrile derivatives and evaluation of therapeutic potential. The synthesis of target molecules has been achieved by reacting 2-aminobenzothiazole and substituted 2-(1-methyl-1H-indole-3-carbonyl)-3,3-bis(methylthio)acrylonitrile in the presence of a catalytic amount of sodium hydride in THF. Structural investigations were carried using 1H NMR, 13C NMR, FT-IR, and HRMS data. In vitro anti-tumor evaluation of the synthesized compounds against MCF-7 (breast carcinoma) cell line revealed that they possess good anti-tumor activities. Compounds, 4j and 4i demonstrated significant activities against breast carcinoma (GI50 14.3 and 19.5 µM respectively). Most of the synthesized compounds were also found to be excellent NO, H2O2, DPPH, and superoxide radical scavengers. Anti-diabetic and antiinflammatory evaluation also displayed moderate activity. Among the compounds synthesized some of the compounds possess significant anticancer, antioxidant and anti-inflammatory properties.

Synthesis and anti-tumor activities of novel 7-O-amino acids chrysin derivatives

ObjectiveTo design and synthesize a series of chrysin derivatives and evaluate the antitumor activities with MTT assay, so as to investigate molecular structure-activity relationship with molecular docking. MethodsTarget products were synthesized with high yield by substitution reaction, hydrolysis reaction, esterification reaction, and saponification reaction in sequence, and activities of all compounds were evaluated with human gastric carcinoma cell lines MGC-803 and human breast carcinoma cell lines MCF-7 through standard MTT assay. Molecular docking results were calculated with Surflex Geom X programme of Sybyl X-2.0 version workstation. Results7-O-amino acids chrysin derivatives 6a–6l were synthesized and their inhibitory effects were evaluated by comparing the material chrysin with positive control drug 5-fluorouracil (5-FU). Among these derivatives, compound 5b (IC50 = 24.50 ± 2.26 µmol/L), 5k (IC50 = 24.30 ± 2.19 µmol/L), and 6f (IC50 = 24.61 ± 2.01 µmol/L) showed better inhibitory activities against MGC-803 cell lines, and compound 5g (IC50 = 13.15 ± 1.73 µmol/L) and 5j (IC50 = 12.34 ± 1.25 µmol/L) showed better inhibitory activities against MCF-7 cell lines than chrysin and 5-FU. Molecular docking scores showed a credible consistency compared with MTT results. ConclusionCompounds 5b, 5d, 5g, 5j, 5k, and 6f showed good antiproliferative effects on specific tumor cells, and compound 5g should be researched further when according to molecular docking.

Facile Synthesis and Anticancer Activity Study of Novel Series of Substituted and Fused Coumarin Derivatives

Various new substituted and fused coumarin analogues have been synthesized via different synthetic pathways. Among which are variable substituted coumarin derivatives bearing either biologically active side chains or rings at 5, 6, and 3 positions of the coumarin nucleus as indicated in compounds 10, 12, 13, 16–19, 21, 23–32, 38, and 42–45. In addition, different pyranocoumarin derivatives either substituted as in compounds 2, 3, and 6 or fused as compounds 33–36, pyranoxanthene analogues such as compounds 4 and 46, coumarinotriazolothiadiazine derivative 8, coumarinonaphthodiazocin analogue 39 and coumarinopyrazolone derivative 40 were synthesized. Thirty‐eight of the synthesized compounds were subjected to in vitro anticancer screening against mammalian liver carcinoma HepG2 and breast carcinoma MCF7 cell lines using Cisplatin as a standard reference. The anticancer activity screening results revealed that, among the tested compounds, compounds 16, 40, and 43 bearing 4‐chlorophenyl‐2‐aminopyridine‐3‐carbonitrile attached to C6 position, fused pyrazolone ring or attached to 4‐chlorophenyl‐2‐oxo‐dihydropyridine‐3‐carbonitrile at C3 position of the coumarin nucleus, respectively, exhibited moderate to strong activity against both cell lines.

Ribociclib shows potential for pharmacokinetic drug-drug interactions being a substrate of ABCB1 and potent inhibitor of ABCB1, ABCG2 and CYP450 isoforms in vitro

Ribociclib is a novel cyclin-dependent kinase (CDK) 4 and 6 selective inhibitor that recently gained breakthrough therapy status and global approval for advanced breast cancer treatment. ATP-binding cassette (ABC) transporters may become a site of severe drug interactions and a mechanism of multidrug resistance (MDR) development. With respect to rapid progress of ribociclib in the clinical field, we aimed to identify its interactions with ABC transporters and cytochrome P450 (CYP) isoenzymes and evaluate its potential to overcome transporter-mediated MDR using established in vitro methods. Our data showed accelerated ABCB1 inhibitor LY335979-sensitive, basolateral-to-apical transport of ribociclib across MDCKII-ABCB1 cell monolayers, which identified ribociclib as an ABCB1 substrate. The antiproliferative studies supported this finding by demonstrating significantly higher EC50 value in ABCB1-, but not ABCG2- or ABCC1-expressing MDCKII cells, than in the parent MDCKII cell line. Furthermore, we observed significant inhibitory effects of ribociclib on ABCB1 and ABCG2 transporters and CYP1A2, CYP3A4, CYP3A5, and CYP2C9 isoform activity in human CYP-expressing insect microsomes. The ribociclib-induced ABCB1 and ABCG2 inhibition further reversed daunorubicin and mitoxantrone resistance in MDCKII and human MCF-7 breast carcinoma cell lines, indicating a synergistic antiproliferative effect, without affecting ABCB1 or ABCG2 expression. In summary, our data indicate that ABCB1 affects ribociclib transport across the membranes and the high potential of ribociclib for drug-drug interactions (DDIs) through ABCB1 and ABCG2 transporters and CYP isoforms. Moreover, we demonstrate the beneficial MDR-reversing potential of ribociclib, which could be further exploited in novel anticancer treatment strategies.

Abstract B43: Validation of a network-based strategy for the optimization of combinatorial target selection in breast cancer therapy

Abstract Network-based strategies provided by systems biology are attractive tools for cancer therapy. Modulation of cancer networks by anticancer drugs may alter the response of malignant cells and/or drive network reorganization into the inhibition of cancer progression. Previously, using systems biology approach and cancer signaling networks, we identified the top 5 highly expressed and connected proteins (HSP90AB1, CSNK2B, TK1, YWHAB, and VIM) in the invasive MDA-MB-231 breast cancer cell line. Here, we have knocked down the expression of these proteins, individually or together using siRNAs. The transfected cell lines were assessed for in vitro cell growth, colony formation, migration, and invasion relative to control transfected MDA-MB-231, the noninvasive MCF-7 breast carcinoma cell line, and the nontumoral mammary epithelial cell line MCF-10A. The knockdown of the top-5 upregulated connectivity hubs successfully inhibited the in vitro proliferation, colony formation, anchorage independence, migration, and invasion in MDA-MB-231 cells, with minimal effects in the control transfected MDA-MB-231 cells or MCF-7 and MCF-10A cells. The in vitro validation of bioinformatics predictions regarding optimized multitarget selection for therapy suggests that protein expression levels together with protein-protein interaction network analysis may provide an optimized combinatorial target selection for a highly effective antimetastatic precision therapy in triple-negative breast cancer. This approach increases the ability to identify not only druggable hubs as essential targets for cancer survival, but also interactions most susceptible to synergistic drug action. The data provided in this report constitute a preliminary step toward the personalized clinical application of our strategy to optimize the therapeutic use of anticancer drugs. Citation Format: Tatiana Martins Tilli, Nicolas Carels, Jack Adam Tuszynski, Manijeh Pasdar. Validation of a network-based strategy for the optimization of combinatorial target selection in breast cancer therapy [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B43.

Synthesis of Pyrazolone Derivatives and Their Nanometer Ag(I) Complexes and Physicochemical, DNA Binding, Antitumor, and Theoretical Implementations.

Four pyrazolone derivatives and their corresponding silver complexes were synthesized and characterized. Based on elemental analysis, 1 : 2 (M : L) molar ratio was suggested for all inspected complexes. 1H, 13C NMR, mass, UV-Vis, TGA, and IR were the spectral tools used for describing the formulae. Moreover, XRD patterns and SEM pictures were used to evaluate the particle sizes which appeared strongly in nanometer range. CT-DNA study is the major consideration in this study, to test the interacting ability of all synthesized cationic complexes towards cell DNA. Each binding constant was computed and correlated with the Hammett sigma constant. Antitumor activity was examined upon three carcinoma cell lines (MCF-7, HepG2, and HCT116). The high efficiency was recorded towards MCF-7 (breast carcinoma) cell line. Kinetic studies yield essential parameters to assert on the rule of metal atom on thermal feature of organic compounds. Molecular modeling was implemented to optimize the structures of compounds. Also, molecular docking was achieved to obtain a clear view about proposed drug behavior within the affected cells. This was achieved through comparing the calculated internal energy values of all docking complexes. All the tested compounds displayed a significant interaction with breast cancer protein (strong matching with practical result) followed by DNA polymerase protein.

Biological Activities of the Alkaloid Quinazoline Extracted from Aspergillus nomius

TWENTY FIVE Aspergillus isolates were screened from Giza Governorate and Saint Catherine Protectorate soils in Egypt. The antimicrobial activity of the crude extracts was tested against two Gram positive bacteria (Bacillus subtilis NRRL-B-4219, Staphylococcus aureus ATCC29213), four Gram negative bacteria (Alcaligenes faecalis B-170, Escherichia coli ATCC25922, Klebsiella pneumoniae ATCC10131, Pseudomonas aeruginosa ATCC27953), and one yeast (Candida albicans ATCC10231). The antioxidant activity using free radical scavenging model was assayed for the crude extracts. The antitumor activity for all of crude extracts was determined against HCT116 (Colon carcinoma cell line), HEPG2 (Liver carcinoma cell line), and MCF-7 (Breast carcinoma cell line). Aspergillus nomius was the most potent fungal species accordingly, it was chosen for bioactivity assay. Identification of this species was further confirmed at the molecular level based on nuclear ribosomal DNA 18s identities. An accession number, LC199488, was given at the DDBJ GenBank. The column chromatography of its crude extract yielded five distinguished fractions. The biological (antimicrobial, antioxidant and antitumor) activities of these fractions were assayed. Fraction B proved to be of most potential. HPLC analysis of this fraction showed that there was a sharp and clear peak at about 18.1 min. This denoted the presence of an active compound. The compound at this peak was purified and its structure was elucidated via 1HNMR and 13CNMR spectroscopy. It was concluded that it would be 1,2,3,9 tetrahydropyrrolo [2,1-b] quinazolin-3-ol.

Antimicrobial, antioxidant and anticancer activities of Laurencia catarinensis, Laurencia majuscula and Padina pavonica extracts

The antimicrobial, antioxidant, and anticancer activities of ethanolic extract of Laurencia catarinensis, L. majuscula and Padina pavonica were determined. The highest antibacterial activity; 23.40 ± 0.58 mm (00.98 µg/ml) and 22.60 ± 2.10 mm (03.90 µg/ml) were obtained against Klebsiella pneumonia by Laurencia catarinensis and Padina pavonica, respectively. However, Padina pavonica showed excellent antibacterial activity against Bacillus subtilis (21.7 ± 1.5 mm; 1.95 µg/ml), Staphylococcus aureus (21.7 ± 0.58 mm; 1.95 µg/ml), Streptococcus pyogenes (20.7 ± 1.2 mm; 1.95 µg/ml) and Acinetobacter baumannii (20.1 ± 1.2 mm; 3.9 µg/ml). Moreover, the highest antifungal activity; 24.7 ± 2.0 mm (0.98 µg/ml), 23.7 ± 1.5 mm (0.98 µg/ml), 23.6 ± 1.5 mm (0.98 µg/ml) was obtained by Padina pavonica against Candida tropicalis, C. albicans and Aspergillus fumigatus, respectively. The algal extracts showed DPPH radical scavenging activity in a concentration–dependent manner with maximum scavenging activity (77.6%, IC50 = 5.59 µg/ml and 77.07%, IC50 = 14.3 µg/ml) was provided by Padina pavonica and Laurenica majuscula, respectively. The in vitro antitumor activity revealed that the IC50 values of Padina pavonica were 58.9, 115.0, 54.5, 59.0, 101.0, 101.0, and 97.6 µg/ml; Laurencia catarinensis were 55.2, 96.8, 104.0, 78.7, 117.0, 217.0, 169.0 µg/ml; and Laurencia. majuscula were 115.0, 221.0, 225.0, 200.0, 338.0, 242.0, and 189.0 µg/ml; respectively against A-549 (Lung carcinoma), Caco-2 (Intestinal carcinoma), HCT-116 (Colon carcinoma), Hela (Cervical carcinoma), HEp-2 (Larynx carcinoma), HepG-2 (Hepatocellular carcinoma), and MCF-7 (Breast carcinoma) cell lines.

Screening Novel Molecular Targets of Metformin in Breast Cancer by Proteomic Approach.

Metformin is a commonly prescribed antihyperglycemic drug, and has been investigated in vivo and in vitro for its effect to improve the comorbidity of diabetes and various types of cancers. Several studies investigated the therapeutic mechanisms of metformin on cancer cells, but the exact mechanism of metformin’s effect on the proteomic pathways of cancer cells is yet to be further investigated. The main objective of our research line is to discover safe and alternative therapeutic options for breast cancer, we aimed in this study to design a novel “bottom up proteomics workflow” in which proteins were first broken into peptides to reveal their identity, then the proteomes were precisely evaluated using spectrometry analysis. In our study, metformin suppressed cell proliferation and induced apoptosis in human breast carcinoma cell line MCF-7 with minimal toxicity to normal breast epithelial cells MCF-10. Metformin induced apoptosis by arresting cells in G1 phase as evaluated by flow cytometric analysis. Moreover, The G1 phase arrest for the MCF-7 has been confirmed by increased expression levels of p21 and reduction in cyclin D1 level. Additionally, metformin increased the expression levels of p53, Bax, Bad while it reduced expression levels of Akt, Bcl-2, and Mdm2. The study employed a serviceable strategy that investigates metformin-dependent changes in the proteome using a literature-derived network. The protein extracts of the treated and untreated cell lines were analyzed employing proteomic approaches; the findings conveyed a proposed mechanism of the effectual tactics of metformin on breast cancer cells. Metformin proposed an antibreast cancer effect through the examination of the proteomic pathways upon the MCF-7 and MCF-10A exposure to the drug. Our findings proposed prolific proteomic changes that revealed the therapeutic mechanisms of metformin on breast cancer cells upon their exposure. In conclusion, the reported proteomic pathways lead to increase the understanding of breast cancer prognosis and permit future studies to examine the effect of metformin on the proteomic pathways against other types of cancers. Finally, it suggests the possibility to develop further therapeutic generations of metformin with increased anticancer effect through targeting specific proteomes.

Synthesis and in vitro anticancer activity of 23(23′)E-benzylidenespirostanols derived from steroid sapogenins

Benzylidenespirostanols were prepared by two-step synthesis including BF3·Et2O-catalyzed aldol condensation of several acetylated steroid sapogenins with benzaldehyde followed by saponification. The obtained compounds showed moderate cytotoxicity against three cancer cell lines (T-lymphoblastic leukemia cell line CEM, breast carcinoma cell line MCF7 and cervical carcinoma cell line HeLa) and normal human fibroblasts (BJ). The most active of the five tested substances was 3c (lowest IC50 for MCF7 cells 19.9±0.1µM) without any selectivity towards human cancer and normal cells, respectively.

The role of p53-microRNA 200-Moesin axis in invasion and drug resistance of breast cancer cells.

This study aimed to analyze the expression of microRNAs in relation to p53 status in breast cancer cells and to delineate the role of Moesin in this axis. We used three isogenic breast carcinoma cell lines MCF7 (with wild-type p53), 1001 (MCF7 with mutated p53), and MCF7-E6 (MCF7 in which p53 function was disrupted). MicroRNA expression was analyzed using microarray analysis and confirmed by real-time polymerase chain reaction. The 1001 clone with mutant p53 showed 22 upregulated and 25 downregulated microRNAs. The predicted targets of these 47 microRNAs were >700 human genes belonging to interesting functional groups such as stem cell development and maintenance. The most significantly downregulated microRNAs in the p53-mutant cell line were from the miR-200 family. We focused on miR-200c which targets many transcripts involved in epithelial-to-mesenchymal transition including Moesin. We found that Moesin was expressed in 1001 but not in its p53 wild-type parental MCF7 consistent with the observed mesenchymal features in the 1001, such as vimentin positivity, E-cadherin negativity, and ZEB1 positivity in addition to the morphological changes. After Moesin silencing, the p53-mutant cells 1001 reverted from mesenchymal-to-epithelial phenotype and showed subtle reduction in migration and invasion and loss of ZEB1 and SNAIL expression. Interestingly, Moesin silencing restored the 1001 sensitivity to Doxorubicin. These results indicate that loss of miR-200c, as a consequence of p53 mutation, can upregulate Moesin oncogene and thus promote carcinogenesis. Moesin may play a role in metastasis and drug resistance of breast cancer.

Estrogenicity assessment of membrane concentrates from landfill leachate treated by the UV-Fenton process using a human breast carcinoma cell line

Membrane concentrates (MCs) are generated when membranes are used to concentrate landfill leachate. It contains high concentrations of inorganic and organic environmental pollutants, which are highly toxic and carcinogenic. In this paper, the proliferation effect (PE) from MC before and after treatment with the UV-Fenton process was assessed using the human breast carcinoma cell line MCF-7. The highest value of 116% was found at 5% (v/v) concentration after a 10 min reaction. Phthalic acid esters (PAEs) play an important role in the MC estrogenicity. Estrogen simulation solutions (ESS) of PAEs were prepared to simulate the changes in estrogenic active substances during the UV-Fenton process. The ESS degradation conformed to the first-order kinetics model. The estrogenicity decreased after an initial increase until it acted in a non-estrogenic manner. Convincingly, the intermediates were determined by GC/MS, and the estrogenicity was assessed during the degradation process. The estrogenicity was highly related to the generation of intermediates and the PAE concentration. The results provide guidance for UV-Fenton application in MC estrogenicity reduction.

Synthesis of extended conjugated indolyl chalcones as potent anti-breast cancer, anti-inflammatory and antioxidant agents

In the present investigation, synthesis of a series of extended conjugated δ-chloro-α-cyano substituted indolyl chalcones (5a–p) was accomplished by reacting 3-cyanoacetylindole 2 with 3-chloro-3-phenyl-propenal 4 in the presence of piperidine. The structural interpretations of newly synthesized compounds were based on chemical and spectroscopic evidences. Anti-tumor evaluation of the synthesized compounds in vitro against MCF-7 (breast carcinoma) cell line revealed that they possess high anti-tumor activities. Among them, compound 5e and 5a demonstrated excellent activity against breast carcinoma (GI50 <0.1 and 4μM respectively) as good as adriamycin (GI50 <0.1μM). The compounds were also screened against the normal Vero monkey cell line, which showed moderate selectivity against inhibition of cancer cells. The effect of extended conjugation on activity authenticated by comparing activity profile of compound 5a, 5i and 5m with their simple analogues. Among the synthesized compounds, 5i and 5l were found to be active anti-inflammatory agents in addition to having noteworthy antioxidant potential. These results suggest the possible use of these compounds for the design and development of novel anti-breast cancer agents.

Comparative Study of Antioxidant and Anticancer Activity of Thuja orientalis Growing in Egypt and Saudi Arabia

Cancer is a life threatening diseases, caused by many factors including the oxidative stress. Some medicinal plants are rich with volatile oil represent an important source of antioxidant and anticancer drugs. This study explored the compositions of the essential oils of the flowering aerial parts of Thuja orientalis (cupressaceae) and evaluated antioxidant and cytotoxic activity against different tumors cell lines. The compositions of the essential oils obtained by hydro-distillation of the flowering aerial parts was determined by GC-MS analysis, the antioxidant activities of essential were determined by DPPH radical scavenging method and, In-vtro cytotoxic activities were evaluated against different tumors cell lines, MCF7 (breast carcinoma cell line), PC3 (human prostate carcinoma), HCT116 (human colon carcinoma), A549 (lung carcinoma cell line), and Hep-G2 (liver carcinoma cell line), by the MTT method. The results showed that essential analyzed sample, very rich in Phellandrene, Terpenyl acetat, and β -Caryophyllene with high amounts. The results showed that essential oil extracted from Saudi plant exhibited higher antioxidant activity. Saudi oil extract also possess highest cytotoxic activities against MCF7, followed by, PC3 and, Hep-G2 while the least activity was recorded against lung carcinoma cell line. The highest antioxidant and cytotoxic activity of Thuja plant growing in Saudi Arabia were correlated with its high content of some compounds which are rich in Saudi plant and absence in Egyptian plant. These findings revealed that plant in two regions could be considered as a great potential source for natural health products, where Saudi plant more adapted to drastic condition by accumulation of higher amount of essential oil.

Antiproliferative and Proapoptotic Activities of Marine Sponge Hyrtios erectus Extract on Breast Carcinoma Cell Line (MCF-7).

Background:Marine sponge is a rich natural resource of many pharmacologically important compounds.Objective:Marine sponge Hyrtios erectus, collected from North Bay, South Andaman Sea, India, was screened for potential antiproliferative and proapoptotic properties on a breast adenocarcinoma cell line (MCF-7).Materials and Methods:3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to test the antiproliferative and cytotoxicity effects of the sponge extract. Analysis of apoptosis and cell cycle stages were done by flow cytometry. The expression of several apoptotic-related proteins in MCF-7 cells treated by the extract was evaluated by Western blot analysis. Various analytical techniques including Fourier transform infrared spectroscopy, gas chromatography-mass spectrometry, and nuclear magnetic resonance were employed to determine the identity of the active compounds in the sponge extract.Results:N-Hexane extract of the sponge inhibited proliferation of the MCF-7 cell line in a dose- and time-dependent manner. Exposure of the sponge extract triggered apoptosis of the MCF-7 cells, induced DNA fragmentation, and arrested the cells in G2/M phase. Treatment of the sponge extract induced downregulation of antiapoptotic Bcl-2 protein and upregulation of Bax, caspase-3, caspase-9, and fragmented poly(ADP ribose)polymerase proteins in MCF-7 cells. Five bioactive compounds have been identified in the extract.Conclusion:The antiproliferative and proapoptotic activities of the tested extract suggested the pharmacologic potential of the identified compounds. Further characterization of the identified compounds are in progress.SUMMARY The N-hexane extract of the marine sponge Hyrtios erectus, collected from North Bay, South Andaman Sea, India, showed potential antiproliferative and proapoptotic properties against a breast adenocarcinoma cell line (MCF-7).The sponge extract retarded the growth of breast carcinoma cell line MCF-7 cells in a time- and dose-dependent manner.The sponge extract induced apoptosis of breast cancer cell line MCF-7 and arrested cells in G2/M phase.The sponge extract induced downregulation of Bcl-2 protein in MCF-7 cell line and upregulation of Bax, caspase-3, and cleaved PARP. Five bioactive compounds have been identified in the extract. Abbreviations used: GC-MS: Gas chromatography-mass spectrometry; FT-IR: Fourier transform infrared spectroscopy; NMR: Nuclear magnetic resonance; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide.