Physical and biological characterization of a growth-inhibitory activity purified from the neuroepithelioma cell line A673

Epithelial- and haematopoietic-cell growth-inhibitory activities have been identified in the conditioned medium of the human peripheral neuroepithelioma cell line A673. An A673-cell-derived growth-inhibitory activity was previously fractionated into two distinct components which inhibited the proliferation of human carcinoma and leukaemia cells in culture. One inhibitory activity was shown to comprise interleukin-1 alpha (IL-1 alpha). Here, we have purified to homogeneity a distinct activity which inhibited the growth of the epithelial cells in vitro. Using a combination of protein-sequence analysis and mass spectrometry, we demonstrated that biological activity can be assigned to a dimeric protein with a molecular mass of 25,576 (+/- 4) Da and an N-terminal sequence identical with that of transforming growth factor-beta 1 (TGF-beta 1). Further characterization of the growth inhibitor with TGF-beta-isoform-specific antibodies showed that > 90% of the bioactivity consists of TGF-beta 1 and not TGF-beta 2 or TGF-beta 3. Although A673 cells were growth-inhibited by exogenous TGF-beta 1, we showed that TGF-beta 1 in A673-cell-conditioned media was present in the latent, biologically inactive, form which did not act as an autocrine growth modulator of A673 cells in vitro.

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Quercetin inhibits the growth of leukemic progenitors and induces the expression of transforming growth factor-beta 1 in these cells

Blood ◽

10.1182/blood.v85.12.3654.bloodjournal85123654 ◽

1995 ◽

Vol 85 (12) ◽

pp. 3654-3661 ◽

Cited By ~ 32

Author(s):

LM Larocca ◽

L Teofili ◽

S Sica ◽

M Piantelli ◽

N Maggiano ◽

...

Keyword(s):

Growth Factor ◽

Transforming Growth Factor Beta ◽

Inhibitory Activity ◽

Transforming Growth Factor ◽

Dependent Manner ◽

Tgf Beta ◽

Acute Leukemias ◽

Growth Inhibitory ◽

Growth Inhibitory Activity ◽

Growth Factor Beta

We previously showed that quercetin (3,3′,4′,5,7 pentahydroxyflavone) inhibits in a dose-dependent manner the growth of acute leukemias and is able to enhance the antiproliferative activity of cytosine arabinoside. We show here that quercetin inhibits the clonogenic activity of 20 of 22 acute leukemias (AL; 4 M1-AML, 3 M2-AML, 2 M3-AML, 3 M4-AML, 3 M5-AML, and 7 ALL). In the present report, we show that the induction of transforming growth factor-beta 1 (TGF-beta 1) in leukemic blasts is one of the growth-inhibitory mechanisms of quercetin in these cells. This observation was supported by the following data. (1) Quercetin-sensitive leukemic blasts, when treated with quercetin, secrete large amounts of TGF-beta 1 in the medium and show positivity for TGF-beta 1-immunoreactive material in the cytoplasm. (2) At a concentration of 8 mumol/L, antisense TGF-beta 1 oligonucleotides prevent the growth-inhibitory action of quercetin. (3) Anti-TGF-beta 1 neutralizing monoclonal antibodies can prevent almost completely the growth-inhibitory activity of quercetin. The analysis of quercetin-resistant cases confirmed as well the central role of TGF-beta 1 in the growth-inhibitory activity of quercetin. In conclusion, quercetin can act as a cytostatic agent for leukemic cells by modulating the production of TGF-beta 1.

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Transforming growth factor beta suppresses human immunodeficiency virus expression and replication in infected cells of the monocyte/macrophage lineage.

Journal of Experimental Medicine ◽

10.1084/jem.173.3.589 ◽

1991 ◽

Vol 173 (3) ◽

pp. 589-597 ◽

Cited By ~ 109

Author(s):

G Poli ◽

A L Kinter ◽

J S Justement ◽

P Bressler ◽

J H Kehrl ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cell ◽

Growth Factor ◽

Cell Line ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Tgf Beta ◽

Immunodeficiency Virus ◽

Growth Factor Beta

The pleiotropic immunoregulatory cytokine transforming growth factor beta (TGF-beta) potently suppresses production of the human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome, in the chronically infected promonocytic cell line U1. TGF-beta significantly (50-90%) inhibited HIV reverse transcriptase production and synthesis of viral proteins in U1 cells stimulated with phorbol myristate acetate (PMA) or interleukin 6 (IL-6). Furthermore, TGF-beta suppressed PMA induction of HIV transcription in U1 cells. In contrast, TGF-beta did not significantly affect the expression of HIV induced by tumor necrosis factor alpha (TNF-alpha). These suppressive effects were not mediated via the induction of interferon alpha (IFN-alpha). TGF-beta also suppressed HIV replication in primary monocyte-derived macrophages infected in vitro, both in the absence of exogenous cytokines and in IL-6-stimulated cultures. In contrast, no significant effects of TGF-beta were observed in either a chronically infected T cell line (ACH-2) or in primary T cell blasts infected in vitro. Therefore, TGF-beta may play a potentially important role as a negative regulator of HIV expression in infected monocytes or tissue macrophages in infected individuals.

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Plasmodium falciparum Line-Dependent Association ofIn VitroGrowth-Inhibitory Activity and Risk of Malaria

Infection and Immunity ◽

10.1128/iai.06190-11 ◽

2012 ◽

Vol 80 (5) ◽

pp. 1900-1908 ◽

Cited By ~ 11

Author(s):

Josea Rono ◽

Anna Färnert ◽

Daniel Olsson ◽

Faith Osier ◽

Ingegerd Rooth ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Inhibitory Activity ◽

Content Type ◽

Phenotypic Differences ◽

Erythrocyte Invasion ◽

Growth Inhibitory ◽

Growth Inhibitory Activity ◽

Control Study

ABSTRACTPlasmodium falciparum's ability to invade erythrocytes is essential for its survival within the human host. Immune mechanisms that impair this ability are therefore expected to contribute to immunity against the parasite. Plasma of humans who are naturally exposed to malaria has been shown to have growth-inhibitory activity (GIA)in vitro. However, the importance of GIA in relation to protection from malaria has been unclear. In a case-control study nested within a longitudinally followed population in Tanzania, plasma samples collected at baseline from 171 individuals (55 cases and 116 age-matched controls) were assayed for GIA using threeP. falciparumlines (3D7, K1, and W2mef) chosen based on their erythrocyte invasion phenotypes. Distribution of GIA differed between the lines, with most samples inhibiting the growth of 3D7 and K1 and enhancing the growth of W2mef. GIA to 3D7 was associated with a reduced risk of malaria within 40 weeks of follow-up (odds ratio, 0.45; 95% confidence interval [CI], 0.21 to 0.96;P= 0.04), whereas GIA to K1 and W2mef was not. These results show that GIA, as well as its association with protection from malaria, is dependent on theP. falciparumline and can be explained by differences in erythrocyte invasion phenotypes between parasite lines. Our study contributes knowledge on the biological importance of growth inhibition and the potential influence ofP. falciparumerythrocyte invasion phenotypic differences on its relationship to protective immunity against malaria.

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Anti-Trypanosomal Alkaloids from Xymalos Monospora

Natural Product Communications ◽

10.1177/1934578x0600100804 ◽

2006 ◽

Vol 1 (8) ◽

pp. 1934578X0600100

Author(s):

Dieudonne Ngamga ◽

Pierre Tane ◽

Donna Rattendi ◽

Cyrus Bacchi ◽

Christopher C. Okunji ◽

...

Keyword(s):

Inhibitory Activity ◽

Stem Bark ◽

Aporphine Alkaloid ◽

African Trypanosomes ◽

Benzylisoquinoline Alkaloids ◽

Benzylisoquinoline Alkaloid ◽

Growth Inhibitory ◽

Growth Inhibitory Activity

From an extract of the stem bark of Xymalos monospora, a bis-benzylisoquinoline alkaloid (1), three benzylisoquinoline alkaloids (mollinedine, 1-(p-methoxybenzyl)-6,7-methylenedioxyisoquino-line, doryafranine), and an aporphine alkaloid (N-methyllaurotetanine) were isolated. These compounds were tested for growth inhibitory activity against bloodstream forms of three strains of African trypanosomes. In vitro IC50 values starting from 1.8 μg /mL were obtained.

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In Vitro Growth-Inhibitory Activity and Malaria Risk in a Cohort Study in Mali

Infection and Immunity ◽

10.1128/iai.00960-09 ◽

2009 ◽

Vol 78 (2) ◽

pp. 737-745 ◽

Cited By ~ 53

Author(s):

Peter D. Crompton ◽

Kazutoyo Miura ◽

Boubacar Traore ◽

Kassoum Kayentao ◽

Aissata Ongoiba ◽

...

Keyword(s):

Inhibitory Activity ◽

Vaccine Development ◽

Critical Role ◽

Malaria Risk ◽

Activity Level ◽

Asexual Blood Stage ◽

Growth Inhibition Assay ◽

Growth Inhibitory ◽

Growth Inhibitory Activity

ABSTRACT Immunity to the asexual blood stage of Plasmodium falciparum is complex and likely involves several effector mechanisms. Antibodies are thought to play a critical role in malaria immunity, and a corresponding in vitro correlate of antibody-mediated immunity has long been sought to facilitate malaria vaccine development. The growth inhibition assay (GIA) measures the capacity of antibodies to limit red blood cell (RBC) invasion and/or growth of P. falciparum in vitro. In humans, naturally acquired and vaccine-induced P. falciparum-specific antibodies have growth-inhibitory activity, but it is unclear if growth-inhibitory activity correlates with protection from clinical disease. In a longitudinal study in Mali, purified IgGs, obtained from plasmas collected before the malaria season from 220 individuals aged 2 to 10 and 18 to 25 years, were assayed for growth-inhibitory activity. Malaria episodes were recorded by passive surveillance over the subsequent 6-month malaria season. Logistic regression showed that greater age (odds ratio [OR], 0.78; 95% confidence interval [95% CI], 0.63 to 0.95; P = 0.02) and growth-inhibitory activity (OR, 0.50; 95% CI, 0.30 to 0.85; P = 0.01) were significantly associated with decreased malaria risk in children. A growth-inhibitory activity level of 40% was determined to be the optimal cutoff for discriminating malaria-immune and susceptible individuals in this cohort, with a sensitivity of 97.0%, but a low specificity of 24.3%, which limited the assay's ability to accurately predict protective immunity and to serve as an in vitro correlate of antibody-mediated immunity. These data suggest that antibodies which block merozoite invasion of RBC and/or inhibit the intra-RBC growth of the parasite contribute to but are not sufficient for the acquisition of malaria immunity.

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Specific growth inhibitory sequences in genomic DNA from quiescent human embryo fibroblasts.

Molecular and Cellular Biology ◽

10.1128/mcb.7.5.1894 ◽

1987 ◽

Vol 7 (5) ◽

pp. 1894-1899 ◽

Cited By ~ 13

Author(s):

R Padmanabhan ◽

T H Howard ◽

B H Howard

Keyword(s):

Dna Sequences ◽

Hela Cells ◽

Human Embryo ◽

Inhibitory Activity ◽

Genomic Dna ◽

Molecular Mechanisms ◽

Growth Inhibitory ◽

Growth Inhibitory Activity ◽

Embryo Fibroblasts

We used HeLa cells as recipients in a gene transfer assay to characterize DNA sequences that negatively regulate mammalian cell growth. In this assay, genomic DNA from quiescent human embryo fibroblasts was more inhibitory for HeLa replication than was DNA from either Escherichia coli or HeLa cells. Surprisingly, growth inhibitory activity depended on the growth state of the cells from which genomic DNA was prepared; it was strongest in DNA prepared from serum-deprived, quiescent embryo fibroblasts. This latter observation implies a role for DNA modification(s) in regulating the activity of the inhibitory sequences detected in our assay. The level of the observed growth inhibitory activity was sometimes high, suggesting that the relevant sequences may be abundantly represented in the mammalian genome. We speculate that these findings may provide new insights into the molecular mechanisms involved in cellular quiescence and in vitro senescence.

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Synthesis of new oxathiazinane dioxides and their in vitro cancer cell growth inhibitory activity

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2009.09.019 ◽

2010 ◽

Vol 20 (17) ◽

pp. 5353-5356 ◽

Cited By ~ 4

Author(s):

Françoise Borcard ◽

Matthias Baud ◽

Claudia Bello ◽

Giovanna Dal Bello ◽

Francesco Grossi ◽

...

Keyword(s):

Cell Growth ◽

Cancer Cell ◽

Inhibitory Activity ◽

Cancer Cell Growth ◽

Growth Inhibitory ◽

Growth Inhibitory Activity

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E-Cadherin Suppresses Cellular Transformation by Inhibiting β-Catenin Signaling in an Adhesion-Independent Manner

The Journal of Cell Biology ◽

10.1083/jcb.153.5.1049 ◽

2001 ◽

Vol 153 (5) ◽

pp. 1049-1060 ◽

Cited By ~ 380

Author(s):

Cara J. Gottardi ◽

Ellen Wong ◽

Barry M. Gumbiner

Keyword(s):

Tumor Suppressor ◽

Cell Line ◽

Inhibitory Activity ◽

Growth Suppression ◽

Binding Region ◽

Suppressor Activity ◽

Growth Inhibitory ◽

Growth Inhibitory Activity ◽

Sw480 Cells ◽

E Cadherin

E-cadherin is a tumor suppressor protein with a well-established role in cell–cell adhesion. Adhesion could contribute to tumor suppression either by physically joining cells or by facilitating other juxtacrine signaling events. Alternatively, E-cadherin tumor suppressor activity could result from binding and antagonizing the nuclear signaling function of β-catenin, a known proto-oncogene. To distinguish between an adhesion- versus a β-catenin signaling–dependent mechanism, chimeric cadherin constructs were expressed in the SW480 colorectal tumor cell line. Expression of wild-type E-cadherin significantly inhibits the growth of this cell line. Growth inhibitory activity is retained by all constructs that have the β-catenin binding region of the cytoplasmic domain but not by E-cadherin constructs that exhibit adhesive activity, but lack the β-catenin binding region. This growth suppression correlates with a reduction in β-catenin/T cell factor (TCF) reporter gene activity. Importantly, direct inhibition of β-catenin/TCF signaling inhibits the growth of SW480 cells, and the growth inhibitory activity of E-cadherin is rescued by constitutively activated forms of TCF. Thus, the growth suppressor activity of E-cadherin is adhesion independent and results from an inhibition of the β-catenin/TCF signaling pathway, suggesting that loss of E-cadherin expression can contribute to upregulation of this pathway in human cancers. E-cadherin–mediated growth suppression was not accompanied by overall depletion of β-catenin from the cytosol and nucleus. This appears to be due to the existence of a large pool of cytosolic β-catenin in SW480 cells that is refractory to both cadherin binding and TCF binding. Thus, a small pool of β-catenin that can bind TCF (i.e., the transcriptionally active pool) can be selectively depleted by E-cadherin expression. The existence of functionally distinct pools of cytosolic β-catenin suggests that there are mechanisms to regulate β-catenin signaling in addition to controlling its level of accumulation.

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