UNIPROT:P08758 - FACTA Search

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Query: UNIPROT:P08758 (annexin V)
9,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Radioimmunotherapy with radiolabeled antibodies may cause inhibition of the growth of epithelial tumors, despite low total radiation doses and comparatively low radiosensitivity of epithelial tumor cells. The induction of apoptosis by low-dose radiation, such as delivered in radioimmunotherapy, was investigated in vitro in human HeLa Hep2 carcinoma cells. The cultured cells were exposed to defined radiation doses from a (60)Co radiation therapy source. The radiation source delivered 0.80 +/- 0.032 (mean +/- SD) Gy/min and the cells were given total doses of 1, 2, 5, 10 and 15 Gy. Using fluorescein-labeled Annexin V, followed by flow cytometry and DNA ladder analysis, apoptotic cells were detected and quantified. Radiation doses below 2 Gy did not cause any significant increase in apoptosis. Compared to control cells, apoptosis was pronounced after 5-10 Gy irradiation and was correlated to the radiation dose, with up to 42 +/- 3.5% of the cells examined displaying apoptosis. Clonogenic assays confirmed significantly decreased viability of the cells in the interval 2 to 10 Gy with low-dose-rate radiation, 60 +/- 2% compared to 2 +/- 2%. Lethal effects on the tumor cells were also evaluated by an assay of the cytotoxic effects of the release of (51)Cr. Significant cytotoxicity, with up to 64 +/- 6% dead cells, was observed at 5 Gy. Similar results were obtained when the dose rate was reduced to 0.072 +/- 0.003 Gy/min (mean +/- SD). In the case of the (137)Cs source, the dose rate could be reduced to 0.045 Gy/h, a level comparable to radioimmunotherapy, which induced significant apoptosis, and was most pronounced at 72-168 h postirradiation. It can be concluded that in vitro low-dose and low-dose-rate radiation induces apoptosis in epithelial HeLa Hep2 cells and thus may explain a mechanism by which pronounced inhibition of growth of HeLa Hep2 tumors at doses used in radioimmunotherapy has been obtained previously.
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PMID:Apoptosis in HeLa Hep2 cells is induced by low-dose, low-dose-rate radiation. 1238 41

Anionic phospholipids are largely absent from the external leaflet of the plasma membrane of mammalian cells under normal conditions. Exposure of phosphatidylserine on the cell surface occurs during apoptosis, necrosis, cell injury, cell activation, and malignant transformation. In the present study, we determined whether anionic phospholipids become exposed on tumor vasculature. A monoclonal antibody, 9D2, which specifically recognizes anionic phospholipids, was injected into mice bearing a variety of orthotopic or ectopic tumors. Other mice received annexin V, a natural ligand that binds to anionic phospholipids. Both 9D2 and annexin V specifically localized to vascular endothelium in all of the tumors, and also to tumor cells in and around regions of necrosis. Between 15 and 40% of endothelial cells in tumor vessels were stained. No localization was detected on normal endothelium. Various factors and tumor-associated conditions known to be present in the tumor microenvironment were examined for their ability to cause exposure of anionic phospholipids in cultured endothelial cells, as judged by 9D2 and annexin V binding. Hypoxia/reoxygenation, acidity, thrombin, and inflammatory cytokines all induced exposure of anionic phospholipids. Hydrogen peroxide was also a strong inducer. Combined treatment with inflammatory cytokines and hypoxia/reoxygenation had greater than additive effects. Possibly, injury and activation of tumor endothelium by cytokines and reactive oxygen species induce exposure of anionic phospholipids, most likely phosphatidylserine. Anionic phospholipids on tumor vessels could potentially provide markers for tumor vessel targeting and imaging.
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PMID:Increased exposure of anionic phospholipids on the surface of tumor blood vessels. 1241 38

Dietary conjugated linoleic acid (CLA) has been shown to reduce colon tumor incidence in rodents by mechanisms probably involving apoptosis. The aim of this study was to evaluate the effects of three commercial CLA preparations (pure c9, t11-CLA, pure t10, c12-CLA and a CLA mixture, containing 29.5% c9, t11 and 29% t10, c12-CLA) on caspase-dependent apoptosis in colon SW480 tumor cells. After 4 days incubation, all CLA-treated cells displayed an increase in caspase 3 (27-34%) and caspase 9 activities (37-47%), cleavage of pro-caspase 3 (32 kDa) to 17 and 12 kDa subunits, increased membrane annexin V levels and reduced expression of bcl-2 compared with untreated controls. Cytosolic cytochrome c was increased (p < 0.05) by all CLA preparations, with the t10, c12-CLA isomer being the most potent. The data indicate that t10, c12-CLA may be the more biologically active isomer for inhibition of colon tumor cell proliferation in vitro.
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PMID:Cis 9, trans 11- and trans 10, cis 12-conjugated linoleic acid isomers induce apoptosis in cultured SW480 cells. 1255 8

p75(NTR) was identified as a tumor and metastasis suppressor that functions in part via induction of apoptosis in tumor cells. To examine p75(NTR)-dependent apoptosis in tumor cells, we demonstrated that a dose-dependent increase in p75(NTR) expression was associated with a concomitant increase in the mitochondrial proapoptotic effector proteins Bad, Bax and Bik and a decrease in the mitochondrial prosurvival effector proteins phospho-Bad, Bcl-2 and Bcl-x(L). Significantly, p75(NTR)-dependent induction of cytochrome c release from the mitochondria occurred during CHX potentiation of apoptosis. Furthermore, p75(NTR) expression largely suppressed expression of IAP-1 and induced cleavage of procaspase-9 and procaspase-7 but not of procaspases 2, 3, 6, 8 and 10. A specific peptide inhibitor of procaspase-9 cleavage also inhibited cleavage of procaspase-7, indicating that caspase-7 is downstream of caspase-9. As end points of apoptosis, we observed p75(NTR)-dependent annexin V binding to the plasma membrane, an indicator of early apoptotic events, and Hoechst staining of DNA nuclear fragmentation, an indicator of late apoptotic events, whereas control tumor cells that lack expression of the p75(NTR) protein did not exhibit either of these apoptotic markers. Together, these results delineate the mitochondria-mediated apoptotic pathway of the p75(NTR) tumor-suppressor gene product.
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PMID:The p75(NTR) tumor suppressor induces caspase-mediated apoptosis in bladder tumor cells. 1267 29

Noninvasive imaging using radioactive annexin V is an emerging strategy for the assessment of cell death in vivo (F. G. Blankenberg, and H. W. Strauss. Apoptosis, 6: 117-123, 2001.). Therefore, we investigated whether annexin V labeled with the fluorophore Cy5.5 (Cy) could serve as a probe for imaging of tumor apoptosis using near infrared fluorescence (NIRF). We prepared active Cy-annexin (an equimolar dye:protein ratio) that bound to apoptotic Jurkat T cells and an inactive Cy-annexin probe (>2 dyes/mol protein) that did not. Active Cy annexin was used to image a 9L gliosarcoma, constitutively expressing green fluorescent protein marker, and the CR8 variant of Lewis lung carcinoma, stably transfected to express DsRed2. The expression of transfected fluorescent protein provided an indication of tumor margins and a means of defining tumor-associated NIRF signal intensity with both tumor models. Tumors were imaged with and without cyclophosphamide treatment. In both tumor models active Cy-annexin V tumor NIRF signal increased two to three times after the treatment. Tumor NIRF signal developed by 75 min after active Cy-annexin injection and remained for a 20-h observation period. Inactive annexin V was used as a control in the CR8 carcinoma experiments and resulted in a low nonspecific signal. With the 9L gliomosacrcoma model, active Cy-annexin V bound to both tumor cells (Cy-annexin V staining only) and endothelial cells (costained with Cy-annexin V and antibody to the endothelial marker CD31). Our results demonstrate that active Cy-annexin can be used as a NIRF probe to image apoptosis from outside an intact living animal and may provide nonradioactive method of measuring the antiproliferative effects of cancer chemotherapeutic regimens.
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PMID:Near-infrared fluorescent imaging of tumor apoptosis. 1270 86

The relative activities of interferon-alpha2b (IFN-alpha2b) and polyethylene glycol(12000)-IFN-alpha2b (PEG-IFN-alpha2b) were assessed in cell culture studies using WM9 melanoma or ACHN renal cell carcinoma cell lines. Interferon-alpha2b and PEG-IFN-alpha2b had identical antiproliferative activities when tested in cell proliferation studies conducted with equivalent antiviral units of each IFN preparation. Neither IFN formulation was effective in inducing apoptosis in WM9 melanoma cells, but both increased slightly the percentage of ACHN cells undergoing apoptosis as assessed by Annexin V staining. Interferon-alpha2b and PEG-IFN-alpha2b both activated signal transducer and activator of transcription complexes, and the duration of complex activation was similar for both IFN formulations. Induction of different IFN-stimulated genes was assessed by Northern blotting and the quantitative real-time reverse transcription-coupled polymerase chain reaction (RT-PCR) in WM9 melanoma, ACHN renal cell carcinoma, U937 lymphoma, and MOLT-4 and Mono Mac 6 leukemia cell lines. Interferon-alpha2b and PEG-IFN-alpha2b had equivalent gene-modulatory activities within each of these tumor cell lines, although cell line-specific induction patterns were observed. When compared with the antiviral 50% inhibitory concentration (IC(50)) values, the dose-dependent gene expression data correlated with cell sensitivity to IFN treatment. Together, the drug comparability and cell sensitivity data suggest a predictive relation between dose, time, antiviral activity, and gene transcription effects. Therefore, although the specific activity of IFN-alpha2b is approximately three times greater than PEG-IFN-alpha2b, the two preparations have identical in vitro biologic activities when applied to cells at equivalent antiviral units.
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PMID:Biologic activity of polyethylene glycol12000-interferon-alpha2b compared with interferon-alpha2b: gene modulatory and antigrowth effects in tumor cells. 1280 74

The current study characterizes the lipogenic enzyme fatty acid synthase (FAS; EC 2.3.1.85) in pediatric tumor cell lines of neural or neural crest origin [medulloblastoma (Daoy), malignant rhabdoid tumor of kidney (SM II), retinoblastoma (Y79), and neuroblastoma (SK-N-SH)]. Constitutive FAS content and activity in these lines were compared to human fibroblast cell line Hs27. Hs27 exhibits low levels of FAS and recapitulates enzyme status in normal human tissues under most physiological conditions. Western analysis detected significantly larger amounts of FAS protein in Y79 and SK-N-SH than Daoy, SM II and Hs27. Incorporation of radiolabeled malonyl-CoA into total cellular lipid revealed that enzyme activity correlated with amount. Increased FAS content and activity in Y79 and SK-N-SH relative to the other cell lines and Hs27, in particular, implied enzyme activation in retinoblastoma and neuroblastoma lineages. The enzyme also showed evidence of hormonal regulation, as dexamethasone induced FAS protein in Daoy and SK-N-SH. However, hormonal induction of FAS protein levels did not correlate with activity levels, which led us to speculate phosphorylation as a means of regulating the enzyme's activity. Finally, the FAS inhibitor cerulenin was investigated for its ability to suppress tumor cell growth. After four days of propagation, short-term treatment of cell lines with drug produced mean IC50s less than 10.5 micrograms/ml (i.e., 5.6 +/- 1.9 for SM II; 9.3 +/- 1.5 for Daoy; 10.2 +/- 0.2 for SK-N-SH; and 10.4 +/- 2.6 for Y79). Annexin V assays revealed that cerulenin initiated apoptosis. The antineoplastic properties of cerulenin documented here are consistent with prior studies showing its cytotoxic effects upon other types of cancer cells and illustrate the potential utility of FAS inhibition as a novel chemotherapeutic approach.
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PMID:Characterization and inhibition of fatty acid synthase in pediatric tumor cell lines. 1282 Mar 77

The active vitamin D metabolite 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) and related substances have previously been tested in tissue culture and animal models of retinoblastoma for their use as anti-tumor drugs. However, despite of the potential therapeutic value, the molecular mechanisms through which 1,25-(OH)(2)D(3) inhibits the growth of retinoblastoma cells are incompletely understood. To elucidate possible signalling pathways for the anti-proliferative action of vitamin D compounds in retinal tumor cells, we analyzed the effect of 1,25-(OH)(2)D(3) and its synthetic analogue KH1060 on the growth of human retinoblastoma-derived Y79 cells. Vitamin D receptor (VDR) mRNA was detected by reverse transcription PCR in Y79 cells and in tissue specimens of human retinoblastoma. VDR transcripts were confirmed at the protein level by strong immunostaining of solid retinal tumors for VDR. Incubation with 1,25-(OH)(2)D(3) and KH1060 (10(-10)-10(-6)moll(-1)) decreased the number of Y79 cells in a timely and dose-dependent manner. Treatment with 1,25-(OH)(2)D(3) (10(-10)moll(-1)) for 24 hr caused cell cycle arrest in the G0/1 phase. Apoptosis of Y79 cells in response to 1,25-(OH)(2)D(3) was demonstrated by the means of TdT-dUTP terminal nick-end labelling (TUNEL), annexin V staining, and detection of DNA fragmentation on agarose gels. 1,25-(OH)(2)D(3)-induced programmed death of Y79 cells was accompanied by a concentration-dependent increase in Bax protein and a reduction in Bcl-2 content. These findings suggest that 1,25-(OH)(2)D(3) inhibits the growth of retinoblastoma cells by causing cell cycle arrest and apoptosis. 1,25-(OH)(2)D(3)-induced programmed death of retinoblastoma cells appears to involve reciprocal changes in Bcl-2 and Bax proteins.
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PMID:1,25-dihydroxyvitamin D3-induced apoptosis of retinoblastoma cells is associated with reciprocal changes of Bcl-2 and bax. 1282 82

Head and neck cancer is a frequent malignancy with a complex, and up to now not clear etiology. Therefore, despite of improvements in diagnosis and therapy, the survival rate with head and neck squamous-cell carcinomas is poor. For a better understanding of the molecular mechanisms behind the process of tumorigenesis and tumor progression, we have analyzed changes of protein expression between microdissected normal pharyngeal epithelium and tumor tissue by ProteinChip technology. For this, cryostat sections from head and neck tumors (n = 57) and adjacent mucosa (n = 44) were laser-microdissected and analyzed on ProteinChip arrays. The derived mass spectrometry profiles exhibited numerous statistical differences. One peak significantly higher expressed in the tumor (p = 0.000029) was isolated by two-dimensional gel electrophoresis and identified as annexin V by in-gel proteolytic digestion, peptide mapping, tandem mass spectrometry analysis, and immuno-deplete assay. The relevance of this single marker protein was further evaluated by immunohistochemistry. Annexin-positive tissue areas were re-analyzed on ProteinChip arrays to confirm the identity of this protein. In this study, we could show that biomarker in head and neck cancer can be found, identified, and assessed by combination of ProteinChip technology, two-dimensional gel electrophoresis, and immunohistochemistry. In our experience, however, such studies only make sense if a relatively pure microdissected tumor tissue is used. Only then minute changes in protein expression between normal pharyngeal epithelium and tumor tissue can be detected, and it will become possible to educe a tumor-associated protein pattern that might be used as a marker for tumorigenesis and progression.
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PMID:Biomarker discovery and identification in laser microdissected head and neck squamous cell carcinoma with ProteinChip technology, two-dimensional gel electrophoresis, tandem mass spectrometry, and immunohistochemistry. 1282 40

Infrared microspectroscopic characterization of radiation-induced apoptosis was used as a new analytical tool to study the kinetics of apoptosis in human peripheral blood lymphocytes at the molecular level. This vibrational technique, which has already been used to investigate biomolecules in normal and tumor cells, allows the simultaneous detection of the biochemical changes in the various subcellular compartments. Normal circulating lymphocytes from five healthy human donors were given a single dose of 6 Gy ((60)Co) and deposited on ZnS windows for infrared spectral acquisition 1, 2 and 4 days after irradiation. Apoptosis was assessed simultaneously by flow cytometry analysis of lymphocytes displaying annexin V-positive staining, and by detection of the DNA laddering that is characteristic of apoptosis. The flow cytometry study showed that about 80% of sham-irradiated lymphocytes were annexin V(neg)/PI(neg) at 1, 2 and 4 days. One day after irradiation, 46% of irradiated lymphocytes were annexin V(neg)/PI(neg), 48% were annexin V(pos)/PI(neg), 5% were annexin V(pos)/PI(pos), and 1% were annexin V(neg)/PI(pos). These mean percentages were respectively 31, 59, 9 and 1 at day 2 and 23, 36, 30, and 11 at day 4. Irradiated lymphocytes presented a DNA laddering pattern characteristic of apoptosis from day 1 after irradiation. In the infrared spectra of irradiated lymphocytes, qualitative and quantitative changes were observed from days 1 and 2, respectively. In the range of 960-1245 cm(-1) mainly attributed to nucleic acids, changes corresponding to conformational changes in DNA were associated with a decrease in the amount of detectable DNA. Conformational changes were also observed in secondary protein structures, in particular an increase in the amount of beta structures. These DNA and protein changes were associated with an increase in the detectable amount of lipids at day 4 after irradiation. These results showed that DNA is probably the first cellular target of radiation-induced apoptosis, which, however, also requires conformational changes and synthesis of cell proteins. Our results are in agreement with biochemical and morphological data on radiation-induced apoptosis of normal human circulating lymphocytes, and they demonstrate that infrared microspectroscopy may be useful for assessing the process of apoptosis at the molecular level.
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PMID:Infrared microspectroscopic characteristics of radiation-induced apoptosis in human lymphocytes. 1285 36

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