Mammary Gland Adenocarcinoma Cell Line Research Articles

Cytotoxic effects of Curcuma longa leaves on MCF-7 and HepG2 cells

Curcuma longa (tumeric) is listed in several therapeutic regimens used in the management of cancer. The present study investigated the potential cytotoxic effects of ethanol extract of Curcuma longa (turmeric) leaves on HepG2 (a human hepatocellular carcinoma cell line), and MCF-7 (a human mammary gland adenocarcinoma cell line) cells. The HepG2 and MCF-7 cells were exposed to different concentrations; 2, 0.2, 0.02, 0.002, 0.0002, 0.00002, 0.000002 μg/ml, of the ethanol extract of C. longa leaves. The Water-Soluble tetrazolium salt (WST-1) assay was used to estimate the cell viability of the cells after which the percentage proliferation was computed. The results of this study indicated that C. longa had cytotoxic effect on the different cell lines, caused a decrease in proliferation and it is more selective to breast cancer cell lines based on the results of WST-1 analysis on the HepG2 and MCF-7 cells. These results suggest that C. longa leaf possesses cytotoxic properties, which can be exploited to develop novel cytotoxic drugs for cancer management. Keywords: Curcuma longa, turmeric, HepG2, MCF-7, WST-1, proliferation, cytotoxic, cancer

In vitro estrogenic, cytotoxic, and genotoxic profiles of the xenoestrogens 8-prenylnaringenine, genistein and tartrazine

Phytoestrogens have been widely praised for their health-promoting effects, whereas synthetic environmental estrogens are considered a toxicological risk to human health. The aim of this study was therefore to compare in vitro the estrogenic, cytotoxic, and genotoxic profiles of three common estrogen-like endocrine-disrupting chemicals: the phytoestrogens 8-prenylnaringenine (8-PN) and genistein and the synthetic xenoestrogen tartrazine. As assessed by a yeast bioreporter assay and estrogen-dependent proliferative response in human mammary gland adenocarcinoma cell line (MCF-7), 8-PN showed the highest estrogen-like activity of the three compounds, followed by tartrazine and genistein. After 24-h incubation on MCF-7 cells, all three compounds exhibited low cytotoxicity in the lactate dehydrogenase assay and no genotoxicity in the micronucleus assay. These results demonstrate that 8-PN, genistein and tartrazine possess variable estrogenic activity but display little cellular toxicity in short-term tests in vitro. No difference between phytoestrogens and a synthetic xenoestrogen could be established.

Effect of vitex agnus castus fruits methanol extract against murine mammary adenocarcinoma cell line (amn3) and rat embryonic fibroblast normal cell line (ref)

Vitex agnus castus showed antiproliferative activity in several previous studies. Angiogenesis is one of the targets in the remediation of cancer. This study aimed to demonstrate the effect of methanol fruits extract of vitex agnus castus on mouse mammary gland adenocarcinoma cell line and rat embryonic fibroblast cell line. The cell lines used in this study were obtained from tissue culture unit/ Iraqi Center for Cancer and Medical Genetic Researches, Al-Mustansiriyah University was maintained in RPMI- 1640 tissue media after preparing from 10% fetal calf serum, antibiotics solution and other materials to make complete growth medium. Serial solutions of vitex agnus castus, methanol crude extract have been tested on 10*4 of AMN3 and REF in each well of 96 well plates. The results of the current study showed that the concentration that inhibits fifty percent of cell line after 72 hours of the experiment (IC50) was 129 ug/ml for AMN3 and 1324ug/ml for REF cell line. The antioxidant activity of Vitex agnus castus may indicate the proliferation inhibition activity of Vitex agnus castus methanol extract. The study concluded that this extract might be of benefit if used in combination with other anti-cancer drugs as adjuvant therapy.

Two new alkaloids from Asparagus stipularis Forssk. roots

Two new alkaloids, aspastipuline (1) and 5-hydroxyaspastipuline (2) were isolated from Asparagus stipularis Forssk. roots. Their structures were elucidated by spectroscopic techniques (1D and 2D NMR, HREIMS). The absolute structure of 2 was established by single-crystal X-ray diffraction analysis. Aspastipuline exhibited a moderate antiproliferative activity against the human mammary gland adenocarcinoma cell line MCF-7.

The Crystal Structure and Cytotoxicity of Centrosymmetric Copper(II) Complex Derived from S-methyldithiocarbazate with Isatin

Copper(II) complex of S-methyldithiocarbazate with isatin has been prepared and screened for their cytotoxic activities against MCF-7 (Human non-metastatic mammary gland adenocarcinoma cell line) and MDA-MB-231 (Human metastatic mammary gland adenocarcinoma cell line). The compound crystallized in an orthorhombic crystal system with a space group C 2cb and was found to be selectively active against MCF-7 cell line (Human non-metastatic mammary gland adenocarcinoma cell line with an IC50 value 0.45 μg/mL. The crystal structure of this centrosymmetric Cu(SMISA)2 complex (SMISA = Schiff base formed by condensation reaction of S-methyldithiocarbazate with isatin) showed that the copper atom has a distorted square-planar geometry with the Schiff base coordinated to the metal ion as a uninegatively charged bidentate ligand through the azomethine nitrogen and thiolate sulfur. Copper(II) complex of S-methyldithiocarbazate with isatin has been prepared and screened for their cytotoxic activities against MCF-7 and MDA-MB-231 breast cancer cell lines. The compound was found to be selectively active against MCF-7 cell line with an IC50 value 0.45 μg/mL.

Curcumin induces apoptosis in a murine mammary gland adenocarcinoma cell line through the mitochondrial pathway

Curcumin, a phenol in turmeric (Curcuma longa), has been studied for the last decade as a potential anticancer drug. It has been shown to reduce viability of the highly malignant, metastatic rat mammary gland cell line ENU1564 in culture and reduce metastasis of these cells injected into nude mice. The purpose of this study was to identify the mechanisms by which curcumin induces apoptosis in these ENU1564 cells in vitro, and to examine its effects on mitochondrial membrane potential and mitochondrial Ca2+ homeostasis. The results show that curcumin induced apoptosis in ENU1564 cells through the intrinsic pathway of apoptosis, as evident by an increase in mitochondrial Ca2+ accumulation and a decrease in mitochondrial membrane potential. However, treatment of the ENU1564 cells with the mitochondrial uniporter inhibitor RU-360 prior to curcumin treatment partially inhibited the curcumin effects. SKF-96365, a store-operated Ca2+ channel blocker, suppressed the curcumin effect on mitochondrial Ca2+. In addition, curcumin down-regulated the expressions of Bcl-2 and procaspase-3 and increased the production of reactive oxygen species in ENU1564 cells. These data suggest that the mitochondrial Ca2+ is the leading factor by which curcumin induced apoptosis in ENU1564 cells, followed by reactive oxygen species production and inhibition of Bcl-2 oncoprotein.

Synthesis, Characterization and Cytotoxic Activity of S-Benzyldithiocarbazate Schiff Bases Derived from 5-Fluoroisatin, 5-Chloroisatin, 5-Bromoisatin and Their Crystal Structures

Schiff bases were prepared from S-benzyldithiocarbazate with 5-fluro-, 5-chloro- and 5-bromoisatin. All are potential tridentate nitrogen, oxygen, sulfur donors. They were found to be selectively active against MCF-7 cell line (Human non-metastatic mammary gland adenocarcinoma cell line). The bromide and fluoride compounds were the most active with IC50 values of 6.40 μM (2.6 μg/mL) and 9.26 μM (3.2 μg/mL) respectively while the chloride derivative was weakly active with an IC50 value of 38.69 μM (14.0 μg/mL). The cytotoxic activity of the halo substituted isatins against the breast cancer cell lines tested is in the order of Br > F > Cl. Planarity of the isatin ring in the Schiff bases can be arranged in the following order SB5FISA > SB5ClISA > SB5BrISA while the perpendicularity of the benzyl ring towards the dithiocarbazate plane can be ordered as follows, SB5FISA > SB5BrISA > SB5ClISA. Schiff bases were prepared from S-benzyldithiocarbazate with 5-fluro-, 5-chloro- and 5-bromoisatin. They were found to be selectively active against MCF-7 cell line (Human non-metastatic mammary gland adenocarcinoma cell line) with the bromide compound was the most active with IC50 value of 6.40 μM (2.6 μg/mL).

Plant-Made Trastuzumab (Herceptin) Inhibits HER2/Neu+ Cell Proliferation and Retards Tumor Growth

BackgroundPlant biotechnology provides a valuable contribution to global health, in part because it can decrease the cost of pharmaceutical products. Breast cancer can now be successfully treated by a humanized monoclonal antibody (mAb), trastuzumab (Herceptin). A course of treatment, however, is expensive and requires repeated administrations of the mAb. Here we used an Agrobacterium-mediated transient expression system to produce trastuzumab in plant cells.Methodology/Principal FindingsWe describe the cloning and expression of gene constructs in Nicotiana benthamiana plants using intron-optimized Tobacco mosaic virus- and Potato virus X-based vectors encoding, respectively, the heavy and light chains of trastuzumab. Full-size antibodies extracted and purified from plant tissues were tested for functionality and specificity by (i) binding to HER2/neu on the surface of a human mammary gland adenocarcinoma cell line, SK-BR-3, in fluorescence-activated cell sorting assay and (ii) testing the in vitro and in vivo inhibition of HER-2-expressing cancer cell proliferation. We show that plant-made trastuzumab (PMT) bound to the Her2/neu oncoprotein of SK-BR-3 cells and efficiently inhibited SK-BR-3 cell proliferation. Furthermore, mouse intraperitoneal PMT administration retarded the growth of xenografted tumors derived from human ovarian cancer SKOV3 Her2+ cells.Conclusions/SignificanceWe conclude that PMT is active in suppression of cell proliferation and tumor growth.

1,3-dihydroxy-5-(tridec-4′,7′-dienyl)benzene: a new cytotoxic compound from Lithraea molleoides

A dichloromethane extract from the leaves of Lithraea molleoides (Anacardiaceae), an argentine medicinal plant, showed cytotoxicity on human hepatocellular carcinoma cell line. Bioassay guided fractionation of this extract led to the isolation of a new active 5-alkyl resorcinol: 1,3-dihydroxy-5-(tridec-4',7'-dienyl)benzene. Chemical structure was established based on spectroscopic data (UV, IR, MS, 1H-NMR, 13C-NMR, COSY). This compound presented cytotoxic activity on 3 human tumoral cell lines: hepatocellular carcinoma cell line-Hep G2 (IC50 +/- SD of 68 +/- 2 microM), mucoepidermoid pulmonary carcinoma cell line-H292 (IC50 +/- SD of 63 +/- 5 microM) and mammary gland adenocarcinoma cell line -MCF7 (IC50 +/- SD of 147 +/- 5).

Method for generation of homogeneous multicellular tumor spheroids applicable to a wide variety of cell types.

Multicellular tumor spheroids (MCTS) are used as organotypic models of normal and solid tumor tissue. Traditional techniques for generating MCTS, such as growth on nonadherent surfaces, in suspension, or on scaffolds, have a number of drawbacks, including the need for manual selection to achieve a homogeneous population and the use of nonphysiological matrix compounds. In this study we describe a mild method for the generation of MCTS, in which individual spheroids form in hanging drops suspended from a microtiter plate. The method has been successfully applied to a broad range of cell lines and shows nearly 100% efficiency (i.e., one spheroid per drop). Using the hepatoma cell line, HepG2, the hanging drop method generated well-rounded MCTS with a narrow size distribution (coefficient of variation [CV] 10% to 15%, compared with 40% to 60% for growth on nonadherent surfaces). Structural analysis of HepG2 and a mammary gland adenocarcinoma cell line, MCF-7, composed spheroids, revealed highly organized, three-dimensional, tissue-like structures with an extensive extracellular matrix. The hanging drop method represents an attractive alternative for MCTS production, because it is mild, can be applied to a wide variety of cell lines, and can produce spheroids of a homogeneous size without the need for sieving or manual selection. The method has applications for basic studies of physiology and metabolism, tumor biology, toxicology, cellular organization, and the development of bioartificial tissue.