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)

Dexrazoxane (DEX) prevents the formation of free radical, lipid peroxidation and cardiotoxicity caused by anthracyclines. Due to a concern about its possible interference with anthracyclin cytotoxicity, the in vitro effect of DEX on daunorubicin (DNR) cytotoxicity, cell cycle and induction of apoptosis by annexin-V was investigated. The sensitivity to DEX, DNR and their combination was tested by the MTT assay in human promyelocytic leukemia HL-60, the erythroid blast crisis CML K562 cell lines and in 45 children with ALL and AML. Cell cycle analysis and annexin-V expression were performed by flow cytometry. It has been observed that DEX itself weakly, but significantly caused cytotoxicity in both cell lines and in patient samples, especially in initial ALL samples. DEX sensitized K562 and HL60, but not patient samples, to cytotoxicity of DNR. The percentage of necrotic/apoptotic cells, as detected in cell cycle analysis and annexin V staining, was higher after exposure to DEX +/- DNR, when compared to respective samples not treated with DEX, in both cell lines but not in patient samples. Expression of annexin V induced by DEX in both cell lines was enlarged, regardless of the presence of DNR. This difference was not observed in patient samples, however, the number of cells expressing annexin V was higher after exposure to DEX +/- DNR in comparison to respective samples not treated with DEX. In conclusion, it seems that DEX possibly has no impact on the sensitivity of childhood leukemic blasts to DNR, however, has weak cytotoxic properties itself.
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PMID:Dexrazoxane has no impact on sensitivity of childhood leukemic blasts to daunorubicin. 1198 42

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

A wide spectrum of anti-cancer activity of genistein and beta-lapachone in various tumors has been reported in single treatments. In this study the combined effects of genistein and beta-lapachone on the chemosensitivity of LNCaP and PC3 human prostate cancer cells was determined in vitro, using 3-[4,5-dimethylthiazol-2-yl]-2-,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) to study treatment-induced growth inhibition and cytotoxicity and, annexin V-fluoresceine (FI) and terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-propidium iodide (PI) assays to determine potential treatment-induced apoptosis and/or necrosis. The results showed: i) that both PC3 and LNCaP are sensitive to single and combination treatments regardless of hormone sensitivity status, ii) that treatment induced dual death pathways (apoptosis and necrosis) in both cell types, iii) that growth inhibition in both cell types correlated positively with cell death via apoptosis at lower drug concentrations and necrosis at higher concentrations, iv) that combination of genistein and beta-lapachone had synergistic inhibitory effects on growth and proliferation in both cell types. The synergistic inhibitory effect was correlated positively with treatment-induced cell death via apoptosis and necrosis. The overall results indicate that combination treatments with beta-lapachone and genistein are more potent in killing both PC3 and LNCaP cancer cells than treatment with either genistein or beta-lapachone alone. beta-lapachone acts at the G1 and S phase checkpoints in the cell cycle, while genistein induces cell cycle arrest at the G2-M stage. The current results are therefore in agreement with the hypothesis that drug combinations that target cell cycles at different critical checkpoints would be more effective in causing cell death. This result provides a rationale for in vivo studies to determine whether beta-lapachone-genistein combination will provide effective chemotherapy for prostate cancer, regardless of the tumor sensitivity to hormone.
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PMID:Chemosensitivity of human prostate cancer cells PC3 and LNCaP to genistein isoflavone and beta-lapachone. 1200 Jan 45

For investigation of the killing and proapoptotic effects of sodium salicylate (Na-Sal) on HL-60 cells, the cytotoxic activity of Na-Sal was measured by means of MTT assay. Apoptosis was identified and analyzed with the help of transmission electron microscopy, annexin V staining, and DNA gel electrophoresis, and the association of caspase-8 activation with apoptosis was determined with the specific protease inhibitor IETD-fmk. After exposure of HL-60 cells to increasing concentrations of Na-Sal (0.5, 1, 3, 5, and 7 mmol/L) for 24 hours, the mean cell viability gradually dropped to 92%, 83%, 68%, 50%, and 42%. With treatment of target cells with 5-mmol/L (IC50) Na-Sal for 6, 12, 24, or 36 hours, the mean cell survival tapered to 91%, 81%, 48% (P <.05 versus control), and 14% (P <.05 versus control). Again incubated with 5-mmol/L Na-Sal for 12 or 24 hours, HL-60 cells displayed clear early or late signs of apoptosis, including (1) notable enhancement of phosphatidylserine externalization, (2) cell shrinkage, membrane blebbing, and eventual disintegration into numerous apoptotic bodies, and (3) formation of ladder DNA. The viability of HL-60 cells increased significantly during 24 or 36 hours of coculture with 100-micromol/L IETD-fmk in combination with 5-mmol/L Na-Sal compared with the viability when 5-mmol/L Na-Sal was used alone (P < .05). Moreover, the target cells showed a considerable decrease in phosphatidylserine exposure and DNA fragmentation after coincubation for 12 or 24 hours performed as described above. The findings presented herein strongly suggest that Na-Sal can exert potent killing and proapoptotic activity against HL-60 cells, and this effect appears to depend on caspase-8 activation.
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PMID:Sodium salicylate-triggered apoptosis in HL-60 cells depends on caspase-8 activation. 1204 73

Ganoderma lucidum has been widely used as a remedy to promote health and longevity in China. The polysaccharide component with a branched (1-->3)-beta-D-glucan moiety from G. lucidum (PS-G) has shown evidence of enhancement of immune responses and of eliciting anti-tumor effects. In this study, we investigated the effect of PS-G on neutrophil viability, which is manifested by spontaneous apoptosis. Annexin V staining and MTT assays reveal that PS-G is able to inhibit spontaneous and Fas-induced neutrophil apoptosis, and this effect of PS-G is enhanced by the presence of zVAD (a caspase inhibitor) and GM-CSF. The antiapoptotic effect of PS-G is diminished by the presence of wortmannin and LY294002 (two PI-3K inhibitors), but is not altered by PD98059 (a MEK inhibitor). Western blotting indicates the stimulating effect of PS-G on Akt phosphorylation and its inhibition of procaspase 3 degradation, which occurs in neutrophils undergoing spontaneous apoptosis or triggered death by Fas. Taken together, PS-G elicitation of antiapoptotic effects on neutrophils primarily relies on activation of Akt-regulated signaling pathways.
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PMID:Polysaccharide purified from Ganoderma lucidum inhibits spontaneous and Fas-mediated apoptosis in human neutrophils through activation of the phosphatidylinositol 3 kinase/Akt signaling pathway. 1210 Dec 82

Up-regulation of Bcl-2 protein may contribute to drug resistance, by decreasing apoptosis after treatment, in pre-B and B-cell leukemias in pediatric patients. By contrast, augmented caspase-3 activity, an effector caspase, may be indicative of drug sensitivity due to increased cellular apoptosis. We have reported the development of an in vitro human T-lymphoblastic leukemia model resistant to ara-C and/or native E. coli L-asparaginase (ASNase), mimicking the drug resistance to the Capizzi II regimen. We have investigated the potential drug synergism between Idarubicin (IDA) and Taxotere (TXR) that may be active in the ara-C and ASNase double drug-resistant cell lines. The additive or synergistic activity between IDA and TXR is drug concentration-dependent in inducing caspase-3 activation and cellular apoptosis. We exposed two human drug-resistant cell lines that do not express the MDRI phenotype, one resistant to ASNase alone (CEM/ASNase-1-3) and the other resistant to both ara-C and ASNase (CEM/ara-C/I/ASNase-0.5-2), to physiologically achievable concentrations of IDA, TXR, or their combination. Both lines showed either synergistic drug activity to the combination regimen in comparison to either drug used alone, as determined by MTT assay, or additivity as demonstrated by flow cytometry after Annexin V and propidium iodide (PI) staining. After exposure of the ASNase-resistant line to various concentrations, the intracellular levels of Bcl-2 protein decreased to near zero relative to untreated control cells. The Bcl-2 protein reductions in these cells ranged from 30% to <1%, 49% to <1%, and 27% to 3% when treated with IDA or TXR as a single drug or IDA + TXR combination, respectively. Similarly, intracellular Bcl-2 levels in the double-resistant cell line decreased with reductions ranging from 24% to <1%, 87% to <1%, and 46% to <1% of the untreated control after treatment with IDA, TXR, or their combination, respectively. Conversely, the caspase-3 activity increased in a dose-dependent manner and inversely-correlated with loss of cell viability (r= 0.91) after exposure to IDA + TXR combination in the double drug-resistant line to both ara-C and ASNase. We conclude that the combination of the IDA + TXR regimen is highly synergistic or additive in drug resistant human leukemic cell clones. The molecular mechanism of action is due to the down-regulation of Bcl-2 protein and up-regulation of caspase-3 activity. This drug combination warrants further investigation for use in the treatment of patients with ara-C and/or ASNase refractory leukemias.
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PMID:The combination regimen of idarubicin and taxotere is effective against human drug-resistant leukemic cell lines. 1216 12

The extracellular matrix (ECM) plays an important role in cell differentiation and apoptosis. Collagen is the major component of ECM. Here, an ESR signal of the hydroxyl radicals (.OH) generated via Fe2+ -mediated Fenton reaction was found to be significantly inhibited by type I collagen. Further study showed that type I collagen also inhibited cell apoptosis induced by.OH, as evidenced by morphological criteria (DAPI and annexin V staining) and quantitive assays for apoptotic cells (MTT and flow-cytometric assay for subG1 cells). By addition of type I collagen in HeLa cells, the lipid peroxidation caused by.OH was inhibited and the cellular GSH was protected. In comparison with type I collagen, BSA and the denatured collagen, gelatin, lacked such antioxidative and antiapoptotic effects. Together, the results suggest that type I collagen can uniquely prevent.OH-mediated apoptosis by scavenging free radicals.
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PMID:Type I collagen inhibits hydroxyl radical-induced apoptosis. 1220 5

Phosphatidic acid, the main product of lipid breakdown through phospholipase D activation, has been implicated in important signal transduction pathways able to influence cell fate in many ways. The purpose of this work was to determine possible effects of phosphatidic acid on neuronal cell death pathways. Here we used cerebellar granular cell cultures and cell death was triggered with either staurosporine or H(2)O(2). Cell viability was quantified by spectrophotometry, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) test. Staurosporine (1-3 microM) or H(2)O(2) (50-800 microM) induced cell death in a dose-dependent manner. Using fluorescent staining (propidium iodide or annexin V-Cy3/6-carboxyfluorescein) we showed that cell death was mostly apoptotic in staurosporine treated cells and mostly non-apoptotic (necrotic) in H(2)O(2) treated cells. Phosphatidic acid was able to increase cell viability in staurosporine-, but not in H(2)O(2) - treated cells. We therefore conclude that phosphatidic acid has neuroprotective potential in neurons exposed to stimuli that trigger apoptosis.
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PMID:Selective protection by phosphatidic acid against staurosporine-induced neuronal apoptosis. 1241 61

In order to investigate the role and the mechanism of protein tyrosine phosphatase (PTPase) signaling pathway in the regulation of proliferation, cell cycle and apoptosis in lymphoma cells, the effects of sodium orthovanadate, Na(3)VO(4), a specific PTPase inhibitor, were explored on Raji lymphoblast-like cell line by MTT assay and CFU-Raji culture, morphologic observation, DNA gel electrophoresis, FCM and RT-PCR. Results showed that MTT assay and CFU-Raji culture demonstrated that sodium or thovanadate inhibited the growth of Raji cells in a concentration-dependent fashion; morphologic observations showed that Raji cells exhibited cytoplasm shrinkage, cytoplasm membrane blebbing, nuclear fragmentation and chromatin condensation forming crescents along nuclear membrane characteristic of apoptosis in the presence of Na(3)VO(4); DNA gel electrophoresis revealed typical DNA ladder reminiscent of DNA cleavage at internucleosomal sites in Na(3)VO(4) treated cells; FCM and RT-PCR indicated that Na(3)VO(4) intervention increased the fraction of annexin V(+) PI(-) cells, reduced the value of mitochondrial transmembrane potential, induced G(2)/M arrest and down-regulated the expression of Bcl-2 and cyclin B1 at both mRNA and protein level in a concentration-dependent manner. It was concluded that PTPase pathway might be implicated in the regulation of cell proliferation, cell cycle and apoptosis, and PTPase specific inhibitor Na(3)VO(4) could induce Raji cell growth inhibition, G(2)/M arrest and apoptosis via down-regulation of Bcl-2 and cyclin B1, and reduction of mitochondrial transmembrane potential.
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PMID:[Effects of sodium orthovanadate on proliferation and apoptosis in raji cells and its mechanism]. 1251 65

The objective of this study was to explore the effect of p21(WAF1) on the sensitivity to chemotherapeutic agent VP-16, etoposide, in leukemia cell line K562. A p21(WAF1) retroviral expression vector was constructed, and mediated by FuGENE(TM)6, it was transfected into K562 cells, which without p21(WAF1) expression. The ecotropic expression of p21(WAF1) in K562 cells was identified by RT-PCR and Western blot, and named K562-p21(WAF1) cell. The K562-p21(WAF1) cells were exposed to VP-16 at different concentrations and different times, then, the sensitivity to VP-16 was examined by cell viability and MTT assay, the apoptosis induced by VP-16 was examined by DNA fragments electrophoresis and flow cytometric Annexin V-PI dual labeling technique. The results showed that the ecotropic expression of p21(WAF1) decreased the sensitivity of K562 cells to VP-16. After treatment of VP-16, the DNA ladder was examined in control K562-neo cells at 20 microgram/ml, but in K562-p21(WAF1) cells at 80 microgram/ml. With FCM, the number of apoptotic K562-neo cells was 14.9% and 25.4% respectively after treated with 20 microgram/ml VP-16 for 12 and 24 hours, and it was 6.94% and 10.96% in K562-p21(WAF1) cells. Our results suggest that the expression of p21(WAF1) could reduce the sensitivity of K562 cells to VP-16 and inhibit the apoptosis of K562 cells
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PMID:[p21(WAF1) transfection decreases sensitivity of K562 cells to VP-16]. 1251 33


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