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)

Amphotericin B is widely used as antifungal drug. Side effects include anemia. A variety of drugs and diseases associated with anemia has recently been shown to trigger suicidal erythrocyte death or eryptosis, i.e. cell membrane scrambling and cell shrinkage. Eryptosis may be triggered by increased cytosolic Ca2+ activity and by lack of ATP. The present study explored whether amphotericin B stimulates eryptosis. Cell membrane scrambling was estimated from annexin V-binding to phosphatidylserine exposed at the cell surface, cell shrinkage from forward scatter in FACS analysis, cytosolic Ca2+ activity from Fluo3 fluorescence and the cytosolic ATP concentration from a luciferase-based assay. Exposure to amphotericin B (0.1-1 microg/ml) within 48 hours significantly increased annexin V-binding, decreased forward scatter, increased cytosolic Ca2+ activity and decreased cytosolic ATP content. In conclusion, amphotericin B stimulates suicidal cell death of erythrocytes, which may in turn contribute to the clearance of circulating erythrocytes and thus to anemia.
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PMID:Triggering of suicidal erythrocyte death by amphotericin B. 1971 May 41

Vitamin K(3) is an essential micronutrient required for the activation of coagulation factors and thus hemostasis. Administration of vitamin K(3) analogues may cause anemia, which at least in theory could be due to stimulation of suicidal erythrocyte death or eryptosis characterized by cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane leading to exposure of phosphatidylserine at the erythrocyte surface. Eryptosis is triggered by an increase in the cytosolic Ca(2+) activity, by ceramide and by energy depletion (decrease of cytosolic ATP). The present experiments explored, whether vitamin K(3) may influence eryptosis. Hemolysis was estimated from the supernatant hemoglobin concentration, phosphatidylserine-exposing erythrocytes from annexin V-binding in fluorescence-activated cell sorter (FACS) analysis, erythrocyte volume from forward scatter in FACS analysis, ceramide formation from binding of fluorescent antibodies, and erythrocyte ATP content from a luciferin-luciferase assay. As a result, vitamin K(3) (> or =1microM) caused lysis of an only small fraction of erythrocytes, but significantly increased ceramide formation, significantly increased the percentage of annexin V-binding erythrocytes, significantly decreased forward scatter and, at higher concentrations, significantly decreased the cellular ATP content. In conclusion, vitamin K(3) stimulates suicidal erythrocyte death, an effect at least partially due to ceramide formation and ATP depletion.
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PMID:Stimulation of ceramide formation and suicidal erythrocyte death by vitamin K(3) (menadione). 1976 12

The purpose of this study is to investigate the efficacy and the mechanism of Hsp90 inhibition of Withaferin A (WA), a steroidal lactone occurring in Withania somnifera, in pancreatic cancer in vitro and in vivo. Withaferin A exhibited potent antiproliferative activity against pancreatic cancer cells in vitro (with IC(50)s of 1.24, 2.93 and 2.78 microM) in pancreatic cancer cell lines Panc-1, MiaPaCa2 and BxPc3, respectively. Annexin V staining showed that WA induced significant apoptosis in Panc-1 cells in a dose-dependent manner. Western blotting demonstrated that WA inhibited Hsp90 chaperone activity to induce degradation of Hsp90 client proteins (Akt, Cdk4 and glucocorticoid receptor), which was reversed by the proteasomal inhibitor, MG132. WA-biotin pull down assay of Hsp90 using Panc-1 cancer cell lysates and purified Hsp90 showed that WA-biotin binds to C-terminus of Hsp90 which was competitively blocked by unlabeled WA. Co-immunoprecipitation exhibited that WA (10 microM) disrupted Hsp90-Cdc37 complexes from 1 to 24h post-treatment, while it neither blocked ATP binding to Hsp90, nor changed Hsp90-P23 association. WA (3, 6mg/kg) inhibited tumor growth in pancreatic Panc-1 xenografts by 30% and 58%, respectively. These data demonstrate that Withaferin A binds Hsp90, inhibits Hsp90 chaperone activity through an ATP-independent mechanism, results in Hsp90 client protein degradation, and exhibits in vivo anticancer activity against pancreatic cancer.
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PMID:Withaferin A targets heat shock protein 90 in pancreatic cancer cells. 1976 45

Dehydroeburicoic acid (DeEA) is a triterpene purified from medicinal fungi such as Antrodia camphorate, the crude extract of which is known to exert cytotoxic effects against several types of cancer cells. We aim to test the hypothesis that DeEA possesses significant cytotoxic effects against glioblastomas, one of the most frequent and malignant brain tumors in adults. 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase release assays indicated that DeEA inhibited the proliferation of the human glioblastoma cell U87MG. In addition, Annexin V and propidium iodide staining showed that DeEA treatment led to a rapid increase of glioblastomas in the necrotic/late apoptotic fraction, whereas cell cycle analysis revealed that DeEA failed to significantly enhance the population of U87MG cells in the hypodiploid (sub-G1) fraction. Using electron microscopy, we found that DeEA induced significant cell enlargements, massive cytoplasmic vacuolization, and loss of mitochondrial membrane integrity. DeEA treatment triggered an intracellular Ca(2+) increase, and DeEA-induced cell death was significantly attenuated by BAPTA-AM but not ethylenediaminetetraacetic acid or ethylene glycol tetraacetic acid. DeEA instigated a reduction of both mitochondrial transmembrane potential and intracellular ATP level. Moreover, DeEA induced proteolysis of alpha-spectrin by calpain, and DeEA cytotoxicity in U87MG cells was caspase-independent but was effectively blocked by calpain inhibitor. Interestingly, DeEA also caused autophagic response that was prevented by calpain inhibitor. Taken together, these results suggest that in human glioblastomas, DeEA induces necrotic cell death that involves Ca(2+) overload, mitochondrial dysfunction, and calpain activation.
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PMID:Dehydroeburicoic acid induces calcium- and calpain-dependent necrosis in human U87MG glioblastomas. 1984 98

Phytic acid, an anticarcinogenic food component, stimulates apoptosis of tumor cells. Similar to apoptosis, human erythrocytes may undergo suicidal death or eryptosis, characterized by cell membrane scrambling and cell shrinkage. Triggers of eryptosis include energy depletion. Phytate intake could cause anemia, an effect attributed to iron complexation. The present experiments explored whether phytic acid influences eryptosis. Supernatant hemoglobin concentration was determined to reveal hemolysis, annexin V-binding in FACS analysis was utilized to identify erythrocytes with scrambled cell membrane, forward scatter in FACS analysis was taken as a measure of cell volume, and a luciferin-luciferase assay was employed to determine erythrocyte ATP content. As a result, phytic acid (>or=1 mM) did not lead to significant hemolysis, but significantly increased the percentage of annexin V-binding erythrocytes, significantly decreased forward scatter, and significantly decreased cellular ATP content. In conclusion, phytic acid stimulates suicidal human erythrocyte death, an effect paralleling its proapoptotic effect on nucleated cells.
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PMID:Effect of phytic acid on suicidal erythrocyte death. 2005 27

3-Bromopyruvate (3BrPA) is a pyruvate analog known for its alkylating property. Recently, several reports have documented the antiglycolytic and anticancer effects of 3BrPA and its potential for therapeutic applications. 3BrPA-mediated cytotoxicity has been evaluated in vitro by various methods including tetrazolium salt (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide)-based assays such as MTT, MTS, and so on. However, growing body of evidences has shown that tetrazolium reagent may interfere with the test compounds. In this study, we investigated whether the tetrazolium reagent interferes with the assessment of 3BrPA cytotoxicity. The results of the tetrazolium-based MTS assay were compared with 3 distinct cell viability detection methods, that is, Trypan Blue staining, ATP depletion, and Annexin V staining in 2 different cell lines, Vx-2 and HepG2. The MTS assay data showed false positive results by indicating increased cell viability at 1 mM and 2 mM 3BrPA whereas the other cell viability assays demonstrated that both Vx-2 and HepG2 cells are not viable at the same treatment conditions. In order to validate the direct interaction of 3BrPA with MTS reagent, we tested cell-free media incubated with different concentrations of 3BrPA. The results of cell-free media showed an increase in absorbance in a dose-dependent manner confirming the interaction of MTS with 3BrPA. Thus, our data clearly demonstrate that 3BrPA interferes with the accuracy of MTS-based cytotoxicity evaluation. Hence, we suggest that employing multiple methods of biochemical as well as morphological cytotoxicity assays is critical to evaluate 3BrPA-mediated cell death.
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PMID:The pyruvic acid analog 3-bromopyruvate interferes with the tetrazolium reagent MTS in the evaluation of cytotoxicity. 2008 59

Crotonaldehyde is a widespread environmental pollutant and lipid peroxidation product. Crotonaldehyde is a risk factor for many diseases (e.g., chronic pulmonary inflammation). However, its toxicity and its mechanism of action have not been thoroughly investigated. The purpose of this study is to investigate crotonaldehyde-induced oxidative stress and mechanism of cell death in BEAS-2B cells. Crotonaldehyde caused decreases of intracellular reduced glutathione levels and increases of reactive oxygen species in a dose-dependent manner. Crotonaldehyde induced cell death by apoptosis, and gradually transitioned to necrosis at high dose of crotonaldehyde, as demonstrated by Annexin V-FITC/PI staining and cell morphology analysis. Crotonaldehyde-induced ATP decline observed in the study might partially account for the switch from apoptosis to necrosis. Mitochondria membrane potential, cytochrome c release, caspase-9, and caspase-3/7 activity were investigated, and the results suggest that crotonaldehyde-induced apoptosis was activated in a caspase-dependent way. Collectively, these results demonstrate crotonaldehyde induces cell oxidative stress and caspase-dependent apoptosis.
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PMID:Crotonaldehyde induces oxidative stress and caspase-dependent apoptosis in human bronchial epithelial cells. 2015 11

The aim of this work was to demonstrate the advantage of using paclitaxel (PTX)-loaded Pluronic P123/F127 mixed micelles (PF-PTX) against non-small cell lung cancer (NSCLC) compared to Taxol. Modulation of multidrug resistance (MDR) by Pluronic mixed micelles was evaluated in lung resistance protein (LRP)-overexpressing human lung adenocarcinoma A-549 cell line. Influence of PF-PTX on in vitro cytotoxicity was determined by MTT assay, while cellular apoptosis was detected by cell nuclei staining and Annexin V-FITC apoptosis detection kit. Cell cycle arrest was also confirmed by flow cytometry. Additionally, in vivo fate and antitumor efficacy of PF-PTX were extensively evaluated in comparison with Taxol. It was demonstrated that PF-PTX had superior anti-proliferation activity against A-549 cells compared with Taxol as measured by IC(50). The enhanced anti-cancer efficacy of PF-PTX was associated with PTX-induced apoptosis and cell arrest in the G(2)/M phase. Intracellular ATP depletion and decreased mitochondrial potential caused by Pluronic copolymers were found to be related to modulation of MDR. PF-PTX also exhibited significant advantages in pharmacokinetics and A-549 xenograft tumor model versus Taxol. The PF-PTX formulation achieved 3.0-fold longer mean residence time in circulation, 2.2-fold larger area under the plasma concentration-time curve than Taxol. At 28days, tumor volume in PF-PTX group was only 31.8% that of the Taxol. Therefore, PF-PTX significantly enhanced the anti-cancer activity of PTX and might be considered a promising drug delivery system to overcome MDR in lung cancer.
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PMID:Enhanced antitumor efficacy by paclitaxel-loaded pluronic P123/F127 mixed micelles against non-small cell lung cancer based on passive tumor targeting and modulation of drug resistance. 2045 5

QA3 is a derivative of the substituted 1,3-dimethyl-1H-quinoxalin-2-ones, which are compounds that may selectively antagonize P-glycoprotein (P-gp) in multidrug resistance (MDR) cancer cells. Our previous work identified QA3 as a candidate compound for reversing MDR in cancer cells. In the present study, we found that QA3 significantly decreases the intracellular level of ATP, stimulates ATPase activity in membrane microsomes and decreases protein kinase C (PKC) activity. These results indicated that QA3 inhibits P-gp activity by blocking ATP hydrolysis and ATP regeneration. Furthermore, QA3 triggered and increased adriamycin-induced K562/A02 cell apoptosis as evidenced by Annexin V-FITC plus PI staining.Western blot analysis showed that the levels of cleaved caspase-9 and cleaved caspase-3 proteins increased, and similarly, the levels of procaspase-9 and procaspase-3 decreased after QA3 treatment. Consequently, poly ADP-ribose polymerase (PARP) activity increased as evidenced by the presence of the PARP cleavage product in K562/A02 cells. QA3 also enhanced the potency of adriamycin against K562/A02 cells as demonstrated by increased apoptosis and activation of caspase-9,-3 and PARP. These data support the observation that P-gp activity is inhibited after QA3 treatment. Moreover, these results indicate that QA3 is a novel MDR reversal agent with potent inhibitory action against P-gp MDR cancer cells.
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PMID:Modulation of P-glycoprotein activity by the substituted quinoxalinone compound QA3 in adriamycin-resistant K562/A02 cells. 2050 89

Eryptosis, the suicidal erythrocyte death, is characterized by cell membrane scrambling and cell shrinkage. Eryptosis may be triggered by excessive hyperosmotic or isosmotic cell shrinkage leading to increase of cytosolic Ca(2+) concentration. Eryptosis is further stimulated by the K(+) ionophore valinomycin, which leads to exit of KCl and osmotically obliged water, or by energy (glucose) depletion, which compromises the function of the Na(+)/K(+) ATPase thus increasing cytosolic Na(+) concentration. The present study explored whether the Na(+) ionophore monensin affects erythrocyte cell volume and eryptosis. The cell membrane scrambling was estimated from binding of annexin V to phosphatidylserine at the erythrocyte surface, cell volume from forward scatter in FACS analysis, cytosolic Ca(2+) concentration from Fluo3 fluorescence and the cytosolic ATP concentration from a luciferase-based assay. Within 24 hours, exposure to monensin (0.1-10 microg/ml) significantly increased forward scatter, cytosolic Ca(2+) concentration and annexin V-binding. Glucose depletion was followed by decreased forward scatter and increased cytosolic Ca(2+) concentration and annexin V-binding. The effect on forward scatter was partially reversed, the effect on cytosolic Ca(2+) concentration and annexin V binding augmented by additional treatment with monensin. In conclusion, monensin dissociates the alterations of cell membrane and cell volume in suicidal erythrocyte death.
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PMID:Monensin induced suicidal erythrocyte death. 2051 20


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