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Human Breast Cancer Cell Lines (human + breast_cancer_cell_line)
Selected AbstractsGinkgo biloba extracts and cancer: a research area in its infancyFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2003Francis V. DeFeudis Abstract Recent studies conducted with various molecular, cellular and whole animal models have revealed that leaf extracts of Ginkgo biloba may have anticancer (chemopreventive) properties that are related to their antioxidant, anti-angiogenic and gene-regulatory actions. The antioxidant and associated anti-lipoperoxidative effects of Ginkgo extracts appear to involve both their flavonoid and terpenoid constituents. The anti-angiogenic activity of the extracts may involve their antioxidant activity and their ability to inhibit both inducible and endothelial forms of nitric oxide synthase. With regard to gene expression, a Ginkgo extract and one of its terpenoid constituents, ginkgolide B, inhibited the proliferation of a highly aggressive human breast cancer cell line and xenografts of this cell line in nude mice. cDNA microarray analyses have shown that exposure of human breast cancer cells to a Ginkgo extract altered the expression of genes that are involved in the regulation of cell proliferation, cell differentiation or apoptosis, and that exposure of human bladder cancer cells to a Ginkgo extract produced an adaptive transcriptional response that augments antioxidant status and inhibits DNA damage. In humans, Ginkgo extracts inhibit the formation of radiation-induced (chromosome-damaging) clastogenic factors and ultraviolet light-induced oxidative stress , effects that may also be associated with anticancer activity. Flavonoid and terpenoid constituents of Ginkgo extracts may act in a complementary manner to inhibit several carcinogenesis-related processes, and therefore the total extracts may be required for producing optimal effects. [source] Oestrogenic activity of benzyl salicylate, benzyl benzoate and butylphenylmethylpropional (Lilial) in MCF7 human breast cancer cells in vitroJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2009A. K. Charles Abstract Benzyl salicylate, benzyl benzoate and butylphenylmethylpropional (Lilial) are added to bodycare cosmetics used around the human breast. We report here that all three compounds possess oestrogenic activity in assays using the oestrogen-responsive MCF7 human breast cancer cell line. At 3 000 000-fold molar excess, they were able to partially displace [3H]oestradiol from recombinant human oestrogen receptors ER, and ER,, and from cytosolic ER of MCF7 cells. At concentrations in the range of 5 × 10,5 to 5 × 10,4 m, they were able to increase the expression of a stably integrated oestrogen-responsive reporter gene (ERE-CAT) and of the endogenous oestrogen-responsive pS2 gene in MCF7 cells, albeit to a lesser extent than with 10,8 m 17, -oestradiol. They increased the proliferation of oestrogen-dependent MCF7 cells over 7 days, which could be inhibited by the antioestrogen fulvestrant, suggesting an ER-mediated mechanism. Although the extent of stimulation of proliferation over 7 days was lower with these compounds than with 10,8 m 17, -oestradiol, given a longer time period of 35 days the extent of proliferation with 10,4 m benzyl salicylate, benzyl benzoate or butylphenylmethylpropional increased to the same magnitude as observed with 10,8 m 17, -oestradiol over 14 days. This demonstrates that benzyl salicylate, benzyl benzoate and butylphenylmethylpropional are further chemical components of cosmetic products which give oestrogenic responses in a human breast cancer cell line in culture. Further research is now needed to investigate whether oestrogenic responses are detectable using in vivo models and the extent to which these compounds might be absorbed through human skin and might enter human breast tissues. Copyright © 2009 John Wiley & Sons, Ltd. [source] Induction or suppression of expression of cytochrome C oxidase subunit II by heregulin , 1 in human mammary epithelial cells is dependent on the levels of ErbB2 expressionJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2002Yanbo Sun The ErbB family of receptor kinases is composed of four members: epidermal growth factor receptor (EGFR/ErbB1), ErbB2/neu, ErbB3, and ErbB4. Amplification of the ErbB2/neu is found in about 30% of breast cancer patients and is associated with a poor prognosis. Heregulin (HRG) activates the ErbB2 via induction of heterodimerization with ErbB3 and ErbB4 receptors. With suppression subtractive hybridization, we demonstrated that the expression of cytochrome c oxidase subunit II (COXII) is HRG-responsive. Two nontransformed human mammary epithelial cell lines, the HB2 and the HB2ErbB2 (the HB2 engineered to overexpress ErbB2), displayed an opposite response to HRG-mediated regulation. HRG upregulated mRNA expression of COXII in the HB2 cells, but suppressed COXII expression in the HB2ErbB2 cells. A human breast cancer cell line (T47D), which expresses ErbB2 at a level similar to that of the HB2 cells, also responded to HRG by increasing COXII mRNA levels. Therefore, HRG regulation of COXII expression depends on the levels of ErbB2 expression. Furthermore, the expression of COXII was inversely correlated to the levels of ErbB2, i.e., the cells overexpressing ErbB2 exhibited lower COXII levels. HRG-evoked signal transduction differed between the cells with normal ErbB expression and the cells overexpressing ErbB2. The activation of both ERK and PI3-K was essential for HRG regulation of COXII, i.e., blockage of either pathway eliminated HRG-mediated alteration. This is the first report demonstrating that the expression of mitochondria-encoded COXII is HRG-responsive. The levels of ErbB2 expression are decisive for the diverse biological activities of HRG. © 2002 Wiley-Liss, Inc. [source] Differential responsiveness of MCF-7 human breast cancer cell line stocks to the pineal hormone, melatoninJOURNAL OF PINEAL RESEARCH, Issue 4 2000Prahlad T. Ram The estrogen receptor (ER)-positive MCF-7 human breast cancer cell line has been used extensively for the study of estrogen-responsive human breast cancer. However, various levels of estrogen responsiveness have been described in different stocks of MCF-7 cells. Because we have previously shown that the pineal hormone, melatonin, inhibits proliferation of MCF-7 cells and can modulate ER expression and transactivation, we investigated if various stocks of MCF-7 cells exhibit a differential responsiveness to the anti-proliferative effects of melatonin and the possible mechanisms involved. The MCF-7 stocks (M, O, H) were examined for: (1) mitogenic response to estradiol; (2) steady-state ER mRNA levels; (3) expression of the mt1 melatonin membrane receptor; (4) growth inhibition by melatonin; and (5) melatonin's modulation of expression of the ER and the estrogen-regulated genes, PgR, TGF, and pS2. For all of these parameters, there was a stock-specific response which showed: MCF-7M>MCF-7O>MCF-7 H. These results demonstrate that there are significant differences in the responsiveness of various stocks of MCF-7 breast cancer cells to the growth-inhibitory effects of melatonin which can be correlated with both the level of ER mRNA expression and the degree of estrogen-responsiveness. These findings suggest that not only may these differences have some impact on the cells' estrogen-response pathway, but also that the primary growth-inhibitory effects of melatonin are transduced through the membrane-associated G-protein coupled mt1 melatonin receptor. [source] Synthesis and Antiproliferative Activitiy of Novel Diaryl Ureas Possessing a 4H- Pyrido[1,2- a]pyrimidin-4-one GroupARCHIV DER PHARMAZIE, Issue 1 2010Peng Yao Abstract We herein disclose a series of novel diaryl urea derivatives possessing a 4H- pyrido[1,2 -a]pyrimidin-4-one group as novel potent anticancer compounds. The structures were confirmed by IR, 1H-NMR, and MS. All the compounds were screened for their antiprofilerative activity agaist the human breast cancer cell line (MDA-MB-231). The pharmacological results indicated that most of the compounds showed moderate activity. The best of this series is compound 4c (IC50 = 0.7 ,mol/L), with a potency 3.6-fold higher than Sorafenib (IC50 = 2.5 ,mol/L), which was approved in 2005. [source] Up-regulation of CD147 and matrix metalloproteinase-2, -9 induced by P-glycoprotein substrates in multidrug resistant breast cancer cellsCANCER SCIENCE, Issue 11 2007Qing-Quan Li Treatment of animals bearing multidrug resistant (MDR) tumor cells with P-glycoprotein (P-gp) substrates could worsen host survival. It is assumed that this is due to increased tumor metastasis. To clarify the mechanism(s) underlying this observation, the MDR human breast cancer cell line, MCF-7/AdrR, and its sensitive parental line, MCF-7, was treated with various concentrations of P-gp substrate drugs (vincristine, paclitoxel, adriamycin) and a P-gp non-substrate drug (bleomycin) in serum-free media. Increased production of CD147, and matrix metalloproteinases (MMP)-2, -9 was observed only in MDR cancer cells exposed to P-gp substrates, as determined using real-time polymerase chain reaction, western blotting and zymography. Correspondingly, P-gp substrates significantly enhanced the in vitro invasion abilities of MCF-7/Adr cells. It was also found that the drug-induced promotion of CD147, and MMP-2, -9 was consistent with increased expression of epidermal growth factor receptor (EGFR) and that inhibition of either EGFR or P-gp activity could significantly interrupt the downstream effects, and so inhibit in vitro invasion abilities motivated by P-gp substrates. These results imply that treatment of MDR tumors with P-gp substrates could adversely affect therapeutic outcomes through modulating the production of CD147, MMP-2, -9, and EGFR, and suggest that this effect may be initiated by the transporter function of P-gp. (Cancer Sci 2007; 98: 1767,1774) [source] An estrogen receptor , suppressor, microRNA-22, is downregulated in estrogen receptor ,-positive human breast cancer cell lines and clinical samplesFEBS JOURNAL, Issue 7 2010Jianhua Xiong Previous studies have suggested that microRNAs (miRNAs) may play important roles in tumorigenesis, but little is known about the functions of most miRNAs in cancer development. In the present study, we set up a cell-based screen using a luciferase reporter plasmid carrying the whole , 4.7 kb 3,-UTR of estrogen receptor , (ER,) mRNA cotransfected with a synthetic miRNA expression library to identify potential ER,-targeting miRNAs. Among all the miRNAs, miR-22 was found to repress robustly the luciferase signal in both HEK-293T and ER,-positive MCF-7 cells. Mutation of the target site was found to abrogate this repression effect of miR-22, whereas antagonism of endogenous miR-22 in MDA-MB-231 cells resulted in elevated reporter signals. We assessed the miR-22 expression patterns in five breast cancer cell lines and 23 clinical biopsies and revealed that there is a significant inverse association between the miR-22 levels and ER, protein expression. To evaluate the potential of miR-22 as a potential therapeutic intervention, we found that reduction of endogenous ER, protein levels and suppression of cancer cell growth could be achieved in MCF-7 cells by miR-22 overexpression in a way that can be recapitulated by the introduction of specific small interfering RNA against ER,. The phenomena can be rescued by the reintroduction of ER,. Taken together, our data indicate that miR-22 was frequently downregulated in ER,-positive human breast cancer cell lines and clinical samples. Direct involvement in the regulation of ER, may be one of the mechanisms through which miR-22 could play a pivotal role in the pathogenesis of breast cancer. [source] Breast cancer-derived Dickkopf1 inhibits osteoblast differentiation and osteoprotegerin expression: Implication for breast cancer osteolytic bone metastasesINTERNATIONAL JOURNAL OF CANCER, Issue 5 2008Guojun Bu Abstract Most breast cancer metastases in bone form osteolytic lesions, but the mechanisms of tumor-induced bone resorption and destruction are not fully understood. Although it is well recognized that Wnt/,-catenin signaling is important for breast cancer tumorigenesis, the role of this pathway in breast cancer bone metastasis is unclear. Dickkopf1 (Dkk1) is a secreted Wnt/,-catenin antagonist. In the present study, we demonstrated that activation of Wnt/,-catenin signaling enhanced Dkk1 expression in breast cancer cells and that Dkk1 overexpression is a frequent event in breast cancer. We also found that human breast cancer cell lines that preferentially form osteolytic bone metastases exhibited increased levels of Wnt/,-catenin signaling and Dkk1 expression. Moreover, we showed that breast cancer cell-produced Dkk1 blocked Wnt3A-induced osteoblastic differentiation and osteoprotegerin (OPG) expression of osteoblast precursor C2C12 cells and that these effects could be neutralized by a specific anti-Dkk1 antibody. In addition, we found that breast cancer cell conditioned media were able to block Wnt3A-induced NF-kappaB ligand reduction in C2C12 cells. Finally, we demonstrated that conditioned media from breast cancer cells in which Dkk1 expression had been silenced via RNAi were unable to block Wnt3A-induced C2C12 osteoblastic differentiation and OPG expression. Taken together, these results suggest that breast cancer-produced Dkk1 may be an important mechanistic link between primary breast tumors and secondary osteolytic bone metastases. © 2008 Wiley-Liss, Inc. [source] Parabens, oestrogenicity, underarm cosmetics and breast cancer: a perspective on a hypothesisJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2003Philip W. Harvey Abstract A recent review by Darbre (2003) published in this journal (J. Appi. Toxicol. 23: 89,95) has attracted public and scienti,c interest that requires perspective, particularly on the use of esters of p -hydroxybenzoic acid (parabens) as preservatives in underarm cosmetics. Although parabens are generally regarded as safe, recent reports suggest that they are oestrogenic in a variety of in vitro (including MCF7 and ZR-75-1 human breast cancer cell lines) and in vivo tests for oestrogenicity (uterotrophic assays in both rat and mouse). There are also recent reports of adverse reproductive and developmental outcomes in rodent toxicity studies. Of interest is the lack of activity by the oral route but clear activity by the subcutaneous and topical routes, which is of some relevance to the use of underarm cosmetics. There would seem to be a case now to supplement these emerging toxicity data with longer term regulatory standard tests examining other oestrogenic endpoints and at least to consider these ,ndings in more up-to-date risk assessments speci,c for cosmetic use. Further, there are few data on the use of underarm cosmetics and the risk of breast cancer, and although one recent retrospective interview-based study found no association there is a need for more thorough investigation taking into account the type of chemicals used. Darbre has forwarded a hypothesis and called for further work to establish whether or not the use of underarm cosmetics (particularly containing oestrogenic formulants) contributes to the rising incidence of breast cancer. It would seem prudent to conduct this work because the current database is sparse and the effects of long-term low-level exposures to weakly oestrogenic chemicals on human health, particularly their application to the underarm and the risks of breast cancer, are unknown. The role of oestrogens in breast cancer, however, is undisputed. Copyright © 2003 John Wiley & Sons, Ltd. [source] High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic abilityJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Alysha K. Croker Abstract Cancer stem cells (CSCs) have recently been identified in leukaemia and solid tumours; however, the role of CSCs in metastasis remains poorly understood. This dearth of knowledge about CSCs and metastasis is due largely to technical challenges associated with the use of primary human cancer cells in pre-clinical models of metastasis. Therefore, the objective of this study was to develop suitable pre-clinical model systems for studying stem-like cells in breast cancer metastasis, and to test the hypothesis that stem-like cells play a key role in metastatic behaviour. We assessed four different human breast cancer cell lines (MDA-MB-435, MDA-MB-231, MDA-MB-468, MCF-7) for expression of prospective CSC markers CD44/CD24 and CD133, and for functional activity of aldehyde dehydrogenase (ALDH), an enzyme involved in stem cell self-protection. We then used fluorescence-activated cell sorting and functional assays to characterize differences in malignant/metastatic behaviour in vitro (proliferation, colony-forming ability, adhesion, migration, invasion) and in vivo (tumorigenicity and metastasis). Sub-populations of cells demonstrating stem-cell-like characteristics (high expression of CSC markers and/or high ALDH) were identified in all cell lines except MCF-7. When isolated and compared to ALDHlowCD44low/, cells, ALDHhiCD44+CD24, (MDA-MB-231) and ALDHhiCD44+CD133+ (MDA-MB-468) cells demonstrated increased growth (P < 0.05), colony formation (P < 0.05), adhesion (P < 0.001), migration (P < 0.001) and invasion (P < 0.001). Furthermore, following tail vein or mammary fat pad injection of NOD/SCID/IL2, receptor null mice, ALDHhiCD44+CD24, and ALDHhiCD44+CD133+ cells showed enhanced tumorigenicity and metastasis relative to ALDHlowCD44low/, cells (P < 0.05). These novel results suggest that stem-like ALDHhiCD44+CD24, and ALDHhiCD44+CD133+ cells may be important mediators of breast cancer metastasis. [source] Phytochemistry and preliminary biological evaluation of Cyathostemma argenteum, a malaysian plant used traditionally for the treatment of breast cancerPHYTOTHERAPY RESEARCH, Issue 7 2004i Khamis Abstract Bioassay guided fractionation of the roots of Cyathostemma argenteum using the brine shrimp resulted in the isolation of two uncommon ,avanones, 2,5-dihydroxy-7-methoxy,avanone 1 and 2,5-dihydroxy-6,7-dimethoxy,avanone 2 while the stem bark yielded the related compounds 5-hydroxy-7-methoxy,avone 3 and 5-hydroxy-6,7-dimethoxy,avone 4. The alkaloids liriodenine 5 and discretamine 6 as well as benzyl benzoate 7 were isolated from the roots and 6 was also isolated from the stembark. In cytotoxicity tests using four human breast cancer cell lines, 1 and 2 were weakly toxic to MCF-7 cells (IC50 = 19.6 and 19.0 µm, respectively) but showed little activity against MCF-7 cells resistant to doxorubicin or against two oestrogen receptor-de,cient cell lines. Compound 5, but not 6 and 7, was moderately cytotoxic against all four cell lines. These results are discussed in the context of the traditional use of C. argenteum in the treatment of breast cancer. Copyright © 2004 John Wiley & Sons, Ltd. [source] Stereochemical Integrity of Oxazolone Ring-Containing JadomycinsCHEMBIOCHEM, Issue 10 2007Charles N. Borissow Dr. Abstract The jadomycins are a series of natural products produced by Streptomyces venzuelae ISP5230 in response to ethanol shock. A unique structural feature of these angucyclines is the oxazolone ring, the formation of which is catalyzed by condensation of a biosynthetic aldehyde intermediate and an amino acid. The feeding of enantiomeric forms of ,-amino acids indicates that the amino acid is incorporated by S. venezuelae ISP5230 without isomerization at the ,-carbon. The characterization of the first two six-membered E-ring-containing jadomycins is reported. These precursor-directed biosynthesis studies indicate flexibility in the acceptor substrate specificity of the glycosyltransferase, JadS. Analysis of cytotoxicity data against two human breast cancer cell lines indicates that the nature of the substitution at the ,-carbon, rather than the stereochemistry, influences biological activity. [source] Synthesis, radiolabeling and in vitro and in vivo characterization of a technetium-99m-labeled alpha-M2 peptide as a tumor imaging agentCHEMICAL BIOLOGY & DRUG DESIGN, Issue 6 2004S.M. Okarvi Abstract:, In an effort to develop a peptide-based radiopharmaceutical for the detection of breast cancer, we have prepared an analog of ,M2 peptide, modified to incorporate an N3S chelate system. Mercaptoacetyltriglycine (MAG)3 -derivatized ,M2 peptide was prepared by solid-phase synthesis and radiolabeled with 99mTc by an exchange method. In vitro cell-binding on human breast cancer cell lines, MDA-MB-231 and MCF-7, indicated the affinity and specificity of 99mTc-MAG3 - ,M2 toward breast cancer cells. Additionally, the radiolabeled peptide showed rapid internalization into human breast cancer cells. In vivo biodistribution in mice showed that the radiolabeled peptide cleared rapidly from the blood and most non-target tissues and was excreted significantly via the kidneys. Uptake of 99mTc-MAG3 - ,M2 in the tumor was moderate. The radiochemical and in vitro and in vivo characterization indicates that the radiolabeled peptide has certain favorable properties and it might be a useful radiopharmaceutical for the detection of breast cancer in vivo. [source] | ||||||||||||||||