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Background and Objective: Breast cancer accounts for about onethird of all cancers in women. Behind lung cancer, it is the second leading cause of cancer deaths in this gender group. In traditional medicine, Euphorbia (E.) microsciadia (Boiss) is a plant used for cancer treatment. Therefore, the main purpose of this study was to determine the effect of E. microsciadia extract on elimination of tumor cells and expression of cytokines in breast cancer MDA-MB- 231 cell line. Materials and Methods: Cell culture was performed in Dulbecco’s Modified Eagle Medium (DMEM); supplemented with 10% fetal bovine serum (FBS), penicillin (1IU/ml), and streptomycin (1μg/ml) at 37°C, with 5% CO2 and 95% humidity. The effect of E. microsciadia extract on the viability of MDA-MB-231 cells was then evaluated by MTT assay. To estimate the expression level of the mRNA of IL-1β, IL-6, IL-8, IL-10, IL-17A, TGF-β1, and INF-γ following MDA-MB-231 cell line treatment with the plant extract, the RNA was extracted using TRIzol solution for cDNA synthesis. The mRNA expression level was subsequently measured in the samples by TaqMan real-time polymerase chain reaction (PCR) technique. The expression of cytokines in both groups of extract treatment and control was ultimately analyzed via Mann-Whitney U test. Results: After 24 and 48 h, the IC50 values for the E. microsciadia extract were determined at 278.30 and 238.20μg/ml, respectively. Besides, the extract showed evidence of anti-proliferative effects on the MDA-MB-231 cell line in a dose- and time-dependent manner. Moreover, the expression levels of INF-γ, IL-8, and IL-1β had significantly increased 24 and 48 h after being treated with E. microsciadia extract. The expression level of TGF-β1, IL-6, IL-10, and IL-17A had correspondingly augmented and decreased after 24 and 48 h of treatment; respectively. Conclusion: The E. microsciadia extract may be used as a tool to manipulate expression of cytokine genes and to ultimately control cell growth and proliferation, which is of utmost importance for molecular and cellular studies in cancer therapy. [ABSTRACT FROM AUTHOR]

Interaction between urokinase-type plasminogen activator (uPA) and its receptor (uPAR) plays an important role in the progression of numerous cancer types including breast cancer by promoting tumor initiating, proliferation, invasion and metastasis. Hence, disruption of this interaction inhibits their downstream cascades and subsequently tumor growth. For this, we created two series of 8 and 10 amino acids linear peptides, derived from uPA binding region to target uPAR and studied the inhibition of proliferation in MDA-MB-231 cell line. Results revealed that all of the 10-mer peptides inhibited breast cancer cell proliferation significantly with maximum 40% inhibition of 103 peptides. Meanwhile, none of the 8-mer peptides showed significant toxicity. Current results indicate that the linear 10-mer peptides which mimic a small part of a sequence of a binding domain of uPA to uPAR could be exploited to design a novel class of anti-cancer agents.

Objectives: Breast cancer is one of the most common types of cancer. Chemotherapeutic agents used during treatment induce cytotoxic effects also on normal cells in the tissues. Anti-oxidants used in combination with chemotherapeutic agents have been shown to reduce toxicity on normal cells to a minimum, and some anti-oxidant substances have chemotherapeutic effects. Cisplatin (CDDP) is a platinum class drug that is used clinically in the treatment of many cancers. Resveratrol (RSV) is a natural polyphenol with potent anti-oxidant and anticancer properties. In this study, we aimed to investigate apoptotic effects of using cisplatin and RSV alone or in combined treatment of MDA-MB-231 cells., Materials and Methods: The cytotoxic effects of the drugs on MDA-MB-231 cells were determined by MTT method. Subsequently, the change in CDDP-induced apoptotic effect after RSV addition was examined using the AnnexinV FITC labeling, and TUNEL staining method. Activation of caspase-9, -3 in MDA-MB-231 cells was measured by flow cytometer. The mitochondrial membrane potential (MMP), the major factor on the intrinsic pathway, was measured using flowcytometry., Results: The combined dose (23 μM CDDP + 72 μM RSV) produced more cytotoxicity than the agents used alone, leading to early apoptosis (8.2%), 31% depolarization, and 23% DNA fragmentation. Caspase-9 was found to be 30.5% in this combined group and caspase-3 was 26.3%., Conclusion: RSV, an effective anti-oxidant, and CDDP as an effective drug in cancer treatment, were found to increase apoptosis when given in the MDA-MB-231 cell.

Triple negative breast cancer is one of the most aggressive breast cancer type with abilities of early metastasis and chemoresistance. The tropical plant Citrus hystrix DC. has been reported to promote many biological activities including anticancer. However, the effect of C. hystrix against triple negative breast cancer has not yet been identified. This study aimed to evaluate the anticancer properties of C. hystrix leaf extract and its bioactive constituents citronellol and citronellal against the triple negative breast cancer MDA-MB-231 cell line. C. hystrix leaves were powdered and sequentially macerated. The in vitro anticancer effects of C. hystrix leaf extracts, and its bioactive constituents (citronellol and citronellal) were evaluated against MDA-MB-231 cell line using cytotoxic MTT assay, cell proliferation, wound scratch migration, colony formation, cell cycle, apoptosis assay, Hoechst staining, RT-qPCR, and Western blot analysis. Results showed that crude hexane extract, citronellol, and citronellal significantly reduced cell proliferation, colony formation, and cell migration by inducing cell cycle arrest, while also inducing apoptosis in MDA-MB-231 cells through inhibition of anti-apoptotic Bcl-2 expression, leading to activation of the caspase-3-dependent pathway. This study is the first report to demonstrate the effect of C. hystrix , citronellol, and citronellal against triple negative breast cancer MDA-MB-231 cells.

Moringa oleifera Lam. (MO) is a medicinal plant distributed across the Middle East, Asia, and Africa. MO has been used in the traditional treatment of various diseases including cancer. This study aimed to perform bioassay-guided fractionation and identification of bioactive compounds from MO leaf against MDA-MB-231 breast cancer cells. MO leaf was sequentially extracted with hexane, ethyl acetate (EtOAc), and ethanol. The most effective extract was subjected to fractionation. MO extract and its derived fractions were continuously screened for anti-cancer activities. The strongest fraction was selected for re-fractionation and identification of bioactive compounds using LC-ESI-QTOF-MS/MS analysis. The best anticancer activities were related to the fraction no. 7-derived crude EtOAc extract. This fraction significantly reduced cell viability and clonogenic growth and increased cells apoptosis. Moreover, sub-fraction no. 7.7-derived fraction no. 7 was selected for the identification of bioactive compounds. There were 10 candidate compounds tentatively identified by LC-ESI-QTOF-MS. Three of identified compounds (7-octenoic acid, oleamide, and 1-phenyl-2-pentanol) showed anticancer activities by inducing cell cycle arrest and triggering apoptosis through suppressed Bcl-2 expression which subsequently promotes activation of caspase 3, indicators for the apoptosis pathway. This study identified 10 candidate compounds that may have potential in the field of anticancer substances.

Cell migration is a fundamental cellular process that plays a crucial role in many physioglogical and pathological processes such as wound healing or cancer metastasis. Many assays have been developed to examine cell migration, such as the wound healing or scratch assay, Boyden Chamber or transwell assay, and the method we will describe here, single cell migration assay. In this assay, cells are plated sparsely on a collagen coated plate and live cell imaging is performed over a period of 2 h at 1 frame per minute. After imaging is completed, cells are tracked manually using ImageJ by tracking movement of the centroid of the cell. These data points are then exported and overall distance travelled from frame to frame is determined and divided by total time imaged to determine speed of the cell. This method provides a quick way to examine effect of cellular manipulation on cell migration before proceeding to perform more complex assays., Competing Interests: Competing interests The authors have no competing interests to report.

Breast cancer is the most recurrently identified and one of women's prominent causes of death. Currently, researchers have turned their focus on natural chemicals from synthetic chemicals due to their environmental, economic, and health benefits. Considering this, the medicinal plant Leucas aspera was chosen for the current study. The aim of this study was to isolate and characterize secondary metabolites from L. aspera and determine the antiproliferative and antimigratory activities in the MDA-MB-231 cell line under in vitro conditions. Phytochemicals from L. aspera were isolated through sequential extraction using hexane, dichloromethane, and ethyl acetate. These extracts were qualitatively screened, subjected to FT-IR, and analyzed using GC-MS. The antiproliferative activity was determined through the MTT assay. Scratch assay was utilized to determine the antimigratory activity of the plant extracts. The phytochemical analysis revealed the presence of steroids, alkaloids, phenols, flavonoids, galactose, tannins, saponins, and amino acids in the extracts. The results of the cell viability assay indicated that the crude dichloromethane and ethyl acetate extracts inhibited cell proliferation, with inhibitory concentrations of 5 and 3 µg/ml, respectively. In contrast, the crude hexane extract did not exhibit any cytotoxicity. Furthermore, the scratch assay results showed that the plant extracts had cell migration inhibitory properties. The outcomes of the current study conclude that L. aspera possesses active therapeutic agents with strong anticancer potential, effectively impeding the proliferation and invasion of MDA-MB-231. Further studies are needed to identify the potential active agents that contribute to these activities. [ABSTRACT FROM AUTHOR]

Multifunctional nanocomposites (NC) can greatly enhance therapy outcomes by reducing tumor proliferative potential. We created a novel class of Zn_Mn_CMC_FA_sesamol NC in the current work to combat breast cancer (MDA-MB-231) cells. To understand how zinc (Zn), manganese (Mn), carboxymethylcellulose, and folic acid (FA) interact with sesamol, UV-Visible spectrophotometer and Fourier Transform Infrared spectroscopy were used to analyze the absorption behavior of the synthesized NC. The particle size of NC was confirmed by X-ray diffraction and dynamic light scattering. Scanning electron microscopy was used to assess the morphological features of these NCs. photoluminescence spectrum was used to analyze the optical and electron transition molecules of the sample. In addition to MTT analysis, acridine orange/ethidium bromide (AO/EtBr) analysis of reactive oxygen species (ROS) and nuclear staining with 4′,6-diamidino-2-phenylindole as well as flow cytometry were used to confirm the apoptotic activity of Zn_Mn_CMC_FA_sesamol NC on MDA-MB-231 cells. The results showed significant cytotoxicity, apoptosis induction on AO/EtBr, and increased ROS production in treated cells compared to control cells. The cell cycle analysis revealed that NCs triggered apoptosis and arrested the cell cycle in G0/G1 phases. As a conclusion, the created NC serves as a versatile platform for the successful molecularly targeted chemotherapeutic treatment of cancer.

The de novo synthesis of glycerolipids in mammalian cells begins with the acylation of glycerol-3-phosphate, catalyzed by glycerol-3-phosphate acyltransferase (GPAT). GPAT2 is a mitochondrial isoform primarily expressed in testis under physiological conditions. Because it is aberrantly expressed in multiple myeloma, it has been proposed as a novel cancer testis gene. Using a bioinformatics approach, we found that GPAT2 is highly expressed in melanoma, lung, prostate and breast cancer, and we validated GPAT2 expression at the protein level in breast cancer by immunohistochemistry. In this case GPAT2 expression correlated with a higher histological grade. 5-Aza-2' deoxycytidine treatment of human cells lines induced GPAT2 expression suggesting epigenetic regulation of gene expression. In order to evaluate the contribution of GPAT2 to the tumor phenotype, we silenced its expression in MDA-MB-231 cells. GPAT2 knockdown diminished cell proliferation, anchorage independent growth, migration and tumorigenicity, and increased staurosporine-induced apoptosis. In contrast, GPAT2 over-expression increased cell proliferation rate and resistance to staurosporine-induced apoptosis. To understand the functional role of GPAT2, we performed a co-expression analysis in mouse and human testis and found a significant association with semantic terms involved in cell cycle, DNA integrity maintenance, piRNA biogenesis and epigenetic regulation. Overall, these results indicate the GPAT2 would be directly associated with the control of cell proliferation. In conclusion, we confirm GPAT2 as a cancer testis gene and that its expression contributes to the tumor phenotype of MDA-MB-231 cells.

A new combination of sulforaphane (a natural compound obtained from Brassicaceae vegetables) and the cytostatic drug doxorubicin was entrapped in nanometer-sized liposomes. In vitro experiments were performed to investigate the cytotoxicity of these structures on the human breast cancer cell line MDA-MB-231. Confocal microscopy studies revealed enhanced cellular endocytotic internalization, followed by the release of the examined combination from the lysosomes. The in vitro interaction analysis using the Chou-Talalay approach showed high synergistic activity of the examined combination. This synergistic activity enables a considerable reduction in cytostatic dosage and an increase in cancer treatment efficiency., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A novel class of chalcones were synthesized via the Claisen-Schmidt condensation of 6-chloropyridine-3-carbaldhyde with various ortho, meta, and para substituted acetophenones in the presence of a base and a polar protic solvent. The newly synthesized compounds were characterized by using various spectral techniques 1H NMR, 13C NMR, FT-IR, and mass spectroscopy methods. All newly synthesized compounds were evaluated in vitro for anticancer activity against the Human Breast Cancer Cell Line MDA-MB-231, and antioxidant activity was quantified using the DPPH free radical scavenging technique. The anticancer screening findings revealed that the synthesized compounds 3a, 3d, 3e, 3f, and 3j had GI50 of

Abstract This work compared the metabolic profile of a parental MDA-MB-231 cisplatin-sensitive triple negative breast cancer (TNBC) cell line with that of a derived cisplatin-resistant line, to characterize inherent metabolic adaptations to resistance, as a means for marker and new TNBC therapies discovery. Supported by cytotoxic, microscopic and biochemical characterization of both lines, Nuclear Magnetic Resonance (NMR) metabolomics was employed to characterize cell polar extracts for the two cell lines, as a function of time (0, 24 and 48 h), and identify statistically relevant differences both between sensitive and resistant cells and their time course behavior. Biochemical results revealed a slight increase in activation of the NF-κB pathway and a marked decrease of the ERK signaling pathway in resistant cells. This was accompanied by lower glycolytic and glutaminolytic activities, possibly linked to glutamine being required to increase stemness capacity and, hence, higher survival to cisplatin. The TCA cycle dynamics seemed to be time-dependent, with an apparent activation at 48 h preferentially supported by anaplerotic aromatic amino acids, leucine and lysine. A distinct behavior of leucine, compared to the other branched-chain-amino-acids, suggested the importance of the recognized relationship between leucine and in mTOR-mediated autophagy to increase resistance. Suggested markers of MDA-MB-231 TNBC cisplatin-resistance included higher phosphocreatine/creatine ratios, hypotaurine/taurine–mediated antioxidant protective mechanisms, a generalized marked depletion in nucleotides/nucleosides, and a distinctive pattern of choline compounds. Although the putative hypotheses generated here require biological demonstration, they pave the way to the use of metabolites as markers of cisplatin-resistance in TNBC and as guidance to develop therapies.

Some medicinal herbs and compounds are known to target cancer cells, but the success of them as anticancer compounds depends to a large extent on their ability to activate pathways that kill cancer cells by arresting cell cycle and inducing apoptosis. The aim of the present study was to determine the anticancer effects of Euphorbia szovitsii Fisch. & C.A.Mey. on the breast cancer cells to reveal the underlying mechanism of its anti-breast cancer properties. In this experimental study, triple negative breast cancer cell line (MDA-MB-231) was cultivated in RPMI-1640 medium. Hydroalcoholic extract (70:30) of aerial parts of the plant was prepared. The cultured cells were treated with different concentrations (0-1000 μg/ml) of E. szovitsii extract for 24 and 48 h. Toxicity of the extract on MDA-MB-231 cells was examined using MTT (3-[4,5-dimethyl-2-thiazolyl]-2, 5 diphenyl tetrazolium bromide) test. The Annexin V-FITC Apoptosis Detection Kit was used to evaluate apoptosis and necrosis. Flow cytometry technique was employed to differentiate different phases of the cell cycle in the cells. Data were analyzed by GraphPad Prism and SPSS software. After 24 and 48 h, the IC50 values were respectively 76.78 (95% CI = 60.75-97.05; R = 0.8588) and 59.71 (95% CI = 46.25-77.09; R = 0.8543) μg/ml for E. szovitsii. The extract exhibited antiproliferative effects against MDA-MB-231 cells in a dose-dependent manner. Annexin V-FITC/PI assay confirmed that the extract was able to induce apoptosis in MDA-MB-231 cells. Moreover, treatment with the extract resulted in cell cycle arrest at G1 phase. Therefore, E. szovitsii could induce apoptosis and cycle arrest in the MDA-MB-231 cell line. It might be a good resource of natural products for producing anti-breast cancer drugs. [ABSTRACT FROM AUTHOR]

In our effort to develop novel and powerful agents with anti-proliferative activity, two new series of 1H-benzo[f]chromene derivatives, 4a-h and 6a-h, were synthesised using heterocyclocondensation methodologies under microwave irradiation condition. The structures of the target compounds were established on the basis of their spectral data, IR, 1H NMR, 13 C NMR, 13 C NMR-DEPT/APT, and MS data. The new compounds have been examined for their anti-proliferative activity against three cancer cell lines, MCF-7, HCT-116, and HepG-2. Vinblastine and Doxorubicin have been used as positive controls in the viability assay. The obtained results confirmed that most of the tested molecules revealed strong and selective cytotoxic activity against the three cancer cell lines. Moreover, these molecules exhibited weak cytotoxicity on the HFL-1 line, which suggested that they might be ideal anticancer candidates. The SAR study of the new benzochromene compounds verified that the substituents on the phenyl ring of 1H-benzo[f]chromene nucleus, accompanied with the presence of bromine atom or methoxy group at the 8-position, increases the ability of these molecules against the different cell lines. Due to their high anti-proliferative activity, compounds 4c and 6e were selected to be examined their proficiency to inhibit the invasiveness of the highly sensitive and invasive breast cancer cell line, MDA-MB-231. The anti-invasion behaviour of these molecules against the highly sensitive, non-oestrogen, and progesterone MDA-MB-231 cell line gave rise to their decreasing metastatic effect compared to the reference drug. Furthermore, this report explores the apoptotic mechanistic pathway of the cytotoxicity of the target compounds and reveals that most of these compounds enhance the Caspase 3/7 activity that could be considered as potential anticancer agents. [ABSTRACT FROM AUTHOR]