Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08758 (annexin V)
 9,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examined the growth inhibitory effects of theasinensin A (from oolong tea) and black tea polyphenols, including theaflavin (TF-1), a mixture (TF-2) of theaflavin-3-gallate (TF-2a) and theaflavin-3'-gallate (TF-2b), and theaflavin-3,3'-digallate (TF-3) in human cancer cells. Theasinensin A, TF-1, and TF-2 displayed strong growth inhibitory effects against human histolytic lymphoma U937, with estimated IC50 values of 12 microM, but were less effective against human acute T cell leukemia Jurkat, whereas TF-3 and (-)-epigallocatechin-3-gallate (EGCG) had lower activities. The molecular mechanisms of tea polyphenol-induced apoptosis as determined by annexin V apoptosis assay, DNA fragmentation, and caspase activation were further investigated. Loss of membrane potential and reactive oxygen species (ROS) generation were also detected by flow cytometry. Treatment with tea polyphenols caused rapid induction of caspase-3, but not caspase-1, activity and stimulated proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). Pretreatment with a potent caspase-3 inhibitor, Z-Asp-Glu-Val-Asp-fluoromethyl ketone, inhibited theasinensin A induced DNA fragmentation. Furthermore, it was found that theasinensin A induced loss of mitochondrial transmembrane potential, elevation of ROS production, release of mitochondrial cytochrome c into the cytosol, and subsequent induction of caspase-9 activity. These results indicate that theasinensin A allows caspase-activated deoxyribonuclease to enter the nucleus and degrade chromosomal DNA and induces DFF-45 (DNA fragmentation factor) degradation. The results suggest that induction of apoptosis by theasinensin A may provide a pivotal mechanism for their cancer chemopreventive function.
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PMID:Induction of apoptosis by the oolong tea polyphenol theasinensin A through cytochrome c release and activation of caspase-9 and caspase-3 in human U937 cells. 1131 5

Induction of apoptosis by different types of pathogenic retroviruses is an important step in disease development. We have observed that infection of thymic lymphocytes by the mink cell focus-forming murine leukemia virus (MCF MLV) during the preleukemic period resulted in an enhancement of apoptosis of these cells. To further study the ability of MCF MLVs to induce apoptosis and the role of this process in viral pathogenesis, we have developed an in vitro system of virus-induced apoptosis. MCF13 MLV infection of mink epithelial cells resulted in the production of cytopathic foci. In contrast, infection of mink cells with the 4070A amphotropic MLV did not produce any cytopathic effects. Staining of MCF13 MLV-infected cells with propidium iodide and annexin V-fluorescein isothiocyanate indicated that virus-induced cell death was due to apoptosis. At 6 days postinfection, the percentage of apoptotic MCF13 MLV-infected cells was 27% compared with 2 to 3% for mock- or amphotropic MLV-infected cells, representing a 9- to 14-fold difference. Assays for caspase-3 activation confirmed the detection by flow cytometry of apoptosis of MCF13 MLV-infected cells. Large amounts of unintegrated linear viral DNA were detectable by Southern blot analysis during the acute phase of infection, which indicated that MCF13 MLV is able to superinfect mink cells. Unintegrated viral DNA of only the linear form was detectable in thymic lymphocytes isolated from MCF13 MLV-inoculated mice during the preleukemic period. These results indicated that the ability of MCF13 MLV to induce apoptosis is correlated with its ability to superinfect cells and that this occurs as an early step in thymic lymphoma development.
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PMID:Mink cell focus-forming murine leukemia virus killing of mink cells involves apoptosis and superinfection. 1139 Jun 2

Glucocorticoids or increases in cellular cAMP promote apoptosis in many cell types, including murine S49 cells. We examined the impact of Bcl-2, an antiapoptotic protein, on S49 cell growth and death promoted by the glucocorticoid dexamethasone or agents that increase cAMP: isoproterenol (a beta-adrenergic agonist) + 3-isobutyl-1-methylxanthine (a phosphodiesterase inhibitor) and forskolin (diterpene). These agents promoted apoptosis (i.e., increased expression of annexin V) of wild-type (WT) S49 cells, but Bcl-2-overexpressing S49 cells were protected from this response. Bcl-2 overexpression did not protect cells from G(1) growth arrest but did allow cells to grow longer in culture and protected cells from culture-dependent necrosis. Commitment to and reversal from apoptosis vs. G(1) growth arrest by isoproterenol + 3-isobutyl-1-methylxanthine showed different kinetics. Although both processes required several hours to develop, removal of agonists readily reversed growth arrest, but not apoptosis. Thus commitment to apoptosis is less reversible than G(1) growth arrest. The findings also indicate that glucocorticoid- and cAMP-mediated G(1) growth arrest is unaffected by Bcl-2 overexpression, even though increased Bcl-2 allows these lymphoma cells to resist necrosis and apoptosis.
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PMID:Bcl-2 protects lymphoma cells from apoptosis but not growth arrest promoted by cAMP and dexamethasone. 1160 Apr 28

Androgens may contribute to higher cardiovascular risk in men via deleterious effects on vascular endothelial cells (EC). We examined the effects of androgens on male human umbilical vein EC (EA.hy926) in culture. [(3)H]Thymidine incorporation assays showed that after 24-h serum deprivation, testosterone (T) (but not dehydroepiandrosterone nor 17beta-E2) induced significant dose-dependent decreases in DNA synthesis (10-16% at 1-100 nmol/liter); the AR antagonist flutamide (100 nmol/liter) abolished this effect of T. After 48-h serum deprivation, typical apoptotic DNA patterns were detected in agarose gels, and the number of floating cells indicative of severe damage was significantly greater after T treatment for 48 and 72 h (13.7 +/- 0.5% and 30.2 +/- 2.5%, respectively) than the control values (9.7 +/- 1.05% and 23.7 +/- 3.0%). Analysis of attached cells by annexin V-fluorescein isothiocyanate/propidium iodide staining showed that after 48-h serum deprivation, T significantly increased the number of cells in the early (16.0 +/- 1.1%) and late (8.3 +/- 0.3%) stages of apoptosis compared with control (6.8 +/- 1.0% and 4.0 +/- 0.2%, respectively); such increases in apoptosis-related damage were also observed, to a lesser degree, in serum-enriched culture. Western blotting showed that B cell leukemia/lymphoma-2 protein (Bcl-2) expression decreased significantly in serum-deprived EC treated with T. Thus, T reduces DNA synthesis and enhances apoptosis after serum deprivation in EC, possibly related to reduced Bcl-2 expression.
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PMID:Testosterone (T) enhances apoptosis-related damage in human vascular endothelial cells. 1186 39

The endogenous viral superantigen 7 in DBA/2 mice serves as a target antigen on syngeneic ESb-MP lymphoma cells for allogeneic graft-vs-leukaemia reactive cells. Allogeneic viral superantigen 7 reactive Vbeta6+ T cells are able to transfer graft-vs-leukaemia reactivity and to kill specifically viral superantigen 7+ ESb-MP tumour cells in vitro. Here we elucidate the mechanism of this superantigen specific cell lysis. Already 10 min after co-incubation with in vitro stimulated Vbeta6+ T cells, viral superantigen 7+ ESb-MP tumour cells show an apoptotic phenotype (Annexin V-positivity, DNA-fragmentation). This extremely rapid type of cell death is not mediated by the death inducing ligands CD95L, TRAIL and TNF but by perforin and granzyme B. Surprisingly, neither mitochondria nor any of the known caspases appear to be involved in this type of tumour cell killing. In contrast, nitric oxide, released by activated macrophages and endothelial cells, induces in the same tumour cells another type of apoptosis which is much slower and involves mitochondria and caspase activation. A synergistic effect between the two different effector mechanisms of superantigen reactive donor cytotoxic T lymphocytes and nitric oxide releasing host macrophages and endothelial cells might explain the effective immune rejection of even advanced metastasised cancer in this graft-vs-leukaemia animal model.
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PMID:Superantigen reactive Vbeta6+ T cells induce perforin/granzyme B mediated caspase-independent apoptosis in tumour cells. 1187 49

This paper evaluates the expression and functional significance of PPAR-gamma on human B cells. Recent interest in PPAR-gamma has focused on its adipogenic effects on non-bone marrow-derived cells. PPAR-gamma agonists also have been proposed as anti-inflammatory agents owing to inhibition of NF-kappa B activation. We report herein the first study evaluating PPAR-gamma expression and functional significance in human B lineage cells. Interestingly, normal human B cells and a variety of B lymphoma cells (e.g., Daudi, Ramos, and Raji) express PPAR-gamma protein as determined by immunocytochemistry. The expression of 80-kDa PPAR-gamma on human B lymphocytes and B lymphomas was confirmed by Western blot analysis. 15-Deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)), a natural PPAR-gamma agonist, has a dose-dependent antiproliferative and cytotoxic effect on normal and malignant B cells as shown by [(3)H]thymidine and MTT assays. Only PPAR-gamma agonists (thiazolidinediones) and not PPAR-alpha agonists mimicked the effect of 15d-PGJ(2) on B lineage cells, indicating that the mechanism by which 15d-PGJ(2) negatively affects B lineage cells involves, in part, PPAR-gamma. The mechanism whereby PPAR-gamma agonists induce cytotoxicity is via apoptosis as shown by Annexin V staining and as confirmed by DNA fragmentation detected using the TUNEL assay. This is the first study evaluating PPAR-gamma expression and its significance on human B lymphocytes. PPAR-gamma agonists may serve as a counterbalance to the stimulating effects of other prostaglandins, namely PGE(2), which promotes B cell immunoglobulin class switching. Finally, the use of prostaglandins such as 15d-PGJ(2) and synthetic PPAR-gamma agonists to induce apoptosis in B lineage cells may lead to the development of novel therapies for potentially fatal B lymphomas.
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PMID:Human B lymphocytes and B lymphomas express PPAR-gamma and are killed by PPAR-gamma agonists. 1198 82

Many therapeutically active anticancer treatments exert their effect by the induction of apoptosis and necrosis. Serial biopsies in breast cancer patients have suggested that response to therapy correlates with early posttreatment increases in tumor apoptotic index. Radiolabeled technetium Tc 99m-recombinant human (rh) annexin V provides a noninvasive technique for imaging treatment-induced cell death. Annexin V is a naturally occurring human protein that binds avidly to membrane-associated phosphatidylserine (PS). PS is normally found only on the inner leaflet of the cell membrane double layer, but it is actively transported to the outer layer as an early event in apoptosis and becomes available for annexin binding. Annexin also gains access to PS as a result of the membrane fragmentation associated with necrosis. In vitro studies of apoptosis using fluorescein annexin have shown good correlation with assessments of apoptosis documented by nuclear DNA degradation and caspase activation. In vivo localization of intravenously administered Tc 99m-annexin V has been demonstrated in numerous preclinical models of apoptosis, including anti-Fas-mediated hepatic apoptosis, rejection of allogeneic heterotopic cardiac allografts, cyclophosphamide treatment of murine lymphoma, cyclophosphamide-induced apoptosis in bone marrow, and leukocyte apoptosis associated with abscess formation. Scintigraphic studies in humans using Tc 99m-rh annexin V have demonstrated the feasibility of imaging cell death in acute myocardial infarction, in tumors with a high apoptotic index, and in response to anti-tumor chemotherapy of non-small cell lung cancer, small-cell lung cancer, breast cancer, lymphoma, and sarcoma. Increased localization of Tc 99m-rh annexin V within 1 to 3 days of chemotherapy has been noted in some, but not all, subjects with these tumors. To date, most subjects showing increased Tc 99m-rh annexin V uptake after the first course of chemotherapy have shown objective clinical responses. A single site study in 15 subjects with 1-year follow-up has suggested that increased posttreatment Tc 99m-rh annexin uptake is associated with improved time to progression of disease and survival time. In vivo imaging of cell death may have the potential to improve the treatment of cancer patients by allowing rapid, objective, patient-by-patient assessment of the efficacy of tumor cell killing.
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PMID:Monitoring apoptosis in real time. 1199 52

Vinorelbine (NVB) is a newly synthesized vinca alkaloid that has been used to treat advanced malignant diseases including lung adenocarcinoma and lymphoma. The effect of NVB on myeloma, however, is unknown. We therefore examined the effect of NVB on the growth of human myeloma cell lines (RPMI8226, U266 and KPMM2) using the trypan blue dye exclusion test and Alamar blue assay. NVB inhibited the growth of myeloma cells of all three cell lines dose-dependently and this effect was intensified when NVB was combined with dexamethasone at 1.0 x 10(-6)mol/l. Flow cytometric analysis using annexin V (AN) and 7-amino-actinomycin D (7AAD) showed that NVB-induced apoptosis of these myeloma cells in all the cell lines. NVB appears to be a potent inducer of apoptosis in myeloma cells, and might have some benefit in the treatment of myeloma patients.
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PMID:Effect of vinorelbine on the growth of human myeloma cell lines in vitro. 1219 68

Eicosapentaenoic acid (EPA; 20:5n-3) may reduce the cell number in cultured leukemia/lymphoma cells owing to reduced cell proliferation, induction of cell death, or a combination of these processes. EPA has been shown to promote apoptosis in Ramos cells, and our present study was focused on a possible cell cycle arrest and the pathways by which the apoptotic process is induced. Apoptosis may proceed along the intrinsic (mitochondrial) or the extrinsic (death receptor) pathway, which are mediated via different caspases. Caspases are a class of homologous cysteine proteases recognized as pivotal mediators of apoptosis. We investigated whether EPA affects progression of the cell cycle or promotes apoptosis directly. By incorporation of [3H]thymidine and [3H]valine, we showed that DNA, as well as protein synthesis, was reduced after incubation of Ramos cells with EPA for 6 h. We monitored cell cycle distribution by 5-bromo-2'-deoxyuridine staining and observed no cell cycle arrest in the EPA-incubated cells. Incubation of cells with EPA caused PS-flipping, as demonstrated by annexin V-binding (flow cytometry), and cleavage of poly(ADP-ribose) polymerase measured by Western blot analysis. Furthermore, we observed increased activity of caspase-3 and -9, but not of caspase-8. Whereas inhibitors of caspase-3 and -9 reduced EPA-induced apoptosis, inhibition of caspase-8 did not. This suggests that EPA may promote apoptosis via the intrinsic pathway in Ramos cells. Thus, the reduction in cell number can be explained by a direct apoptotic effect of EPA rather than via cell cycle arrest.
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PMID:Eicosapentaenoic acid promotes apoptosis in Ramos cells via activation of caspase-3 and -9. 1237 51

Monensin, a Na+ ionophore, regulates many cellular functions, including apoptosis. We investigated the in vitro antiproliferative effect of monensin on nine human lymphoma cell lines. Monensin significantly inhibited the proliferation of all the lymphoma cell lines examined with a 50% inhibition concentration of about 0.5 micromol/l, and induced a G1 and/or a G2-M phase arrest in these cell lines. To address the antiproliferative mechanism of monensin, we examined the effect of this drug on cell-cycle-related proteins in CA46 cells (both G1 and G2 arrest) and Molt-4 cells (G2 arrest). Treatment with monensin for 72 h decreased CDK4 and cyclin A levels in CA46 cells, and cdc2 levels in Molt-4 cells. In monensin-treated CA46 cells, increased p21-CDK2, p27-CDK2 and p27-CDK4 complex forms were observed. And, in monensin-treated Molt-4 cells, increased p21-cdc2 complex form was detected. Furthermore, the activities of CDK2- and CDK4-associated kinases were reduced in association with Rb hypophosphorylation in monensin-treated CA46 cells. The activity of cdc2-associated kinase was decreased in both cell lines, which was accompanied by induction of Wee1. Also, monensin induced apoptosis in these cell lines, as evidenced by annexin V binding assay and flow cytometric detection of sub-G1 DNA content. This apoptotic process was associated with loss of mitochondria transmembrane potential (Delta(psi)m). Taken together, these results demonstrated for the first time that monensin potently inhibits the proliferation of human lymphoma cell lines via cell cycle arrest and apoptosis.
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PMID:Monensin-mediated growth inhibition in human lymphoma cells through cell cycle arrest and apoptosis. 1240 77


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