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

Effects of hydrogen peroxide (H(2)O(2)) on rat thymocytes were examined, using a flow cytometer and three fluorescent probes, annexin V-fluorescein isothiocyanate (annexin V-FITC) for detecting phosphatidylserine expressed on the membrane surface, ethidium bromide for estimating dead cells, and fluo-3-acetoxymethyl ester (fluo-3-AM) for monitoring changes in intracellular Ca(2+) concentration ([Ca(2+)](i)), to characterize H(2)O(2)-induced cytotoxicity. Exposure to H(2)O(2) (30 microM or more) increased the number of annexin V-positive live cells dose- and time-dependently while the number of dead cells increased at concentrations of 1 mM or more. H(2)O(2) (30 microM or more) increased [Ca(2+)](i) in a dose-dependent manner. Threshold concentration of H(2)O(2) to increase [Ca(2+)](i) was similar to that to increase annexin V binding to membranes. The H(2)O(2)-induced change in cell membranes was attenuated under Ca(2+)-free conditions. Therefore, it is likely that Ca(2+) is involved in the H(2)O(2)-induced cytotoxicity. Deferoxamine was effective to protect the cells suffering from H(2)O(2)-induced oxidative stress, suggesting a contribution of hydroxyl radicals generated by the Fenton reaction. Quercetin also exerted a potent protective action on cells suffering from H(2)O(2)-induced oxidative stress. The results indicate that the exposure of rat thymocytes to H(2)O(2) at micromolar concentrations increases annexin V binding to cell membranes in a Ca(2+)-dependent manner, suggesting the possibility that the oxidative stress caused by H(2)O(2) (and/or hydroxyl radicals) induces apoptosis via increasing [Ca(2+)](i).
 ...
PMID:Exposure of rat thymocytes to hydrogen peroxide increases annexin V binding to membranes: inhibitory actions of deferoxamine and quercetin. 1061 19

Quercetin and flavopiridol, both flavonoids which influence oxidative milieu, proliferation, and apoptosis of various cell types, were examined for their effects on acute myelogenous leukemic cells and normal progenitors. Both quercetin and flavopiridol inhibited the growth and viability of various acute myelogenous leukemia (AML) cell lines and AML blasts isolated afresh from patients with AML of various subtypes. The effects on inhibition of proliferation and decreased viability were also significant in normal CD34+ cells isolated from normal marrow donors. In certain AML cases, the effects of flavopiridol appeared to be mediated through activation of caspase 3, offering one possible mechanism for the apoptosis evident after exposure to flavopiridol as measured by annexin V expression. These flavonoid compounds might find use in various therapeutic settings in AML.
 ...
PMID:Flavonoid effects on normal and leukemic cells. 1264 4

In addition to parasite spread, the severity of disease observed in cases of human African trypanosomiasis (HAT), or sleeping sickness, is associated with increased levels of inflammatory mediators, including tumor necrosis factor (TNF)-alpha and nitric oxide derivatives. In the present study, quercetin (3,3',4',5,7-pentahydroxyflavone), a potent immunomodulating flavonoid, was shown to directly induce the death of Trypanosoma brucei gambiense, the causative agent of HAT, without affecting normal human cell viability. Quercetin directly promoted T. b. gambiense death by apoptosis as shown by Annexin V binding. In addition to microbicidal activity, quercetin induced dose-dependent decreases in the levels of TNF-alpha and nitric oxide produced by activated human macrophages. These results highlight the potential use of quercetin as an antimicrobial and anti-inflammatory agent for the treatment of African trypanomiasis.
 ...
PMID:Quercetin induces apoptosis of Trypanosoma brucei gambiense and decreases the proinflammatory response of human macrophages. 1498 85

Evidence has accumulated that dietary polyphenols, in particular, flavonoids, have protective effects against oral cancer. In this study, we have examined the effects of quercetin, a major dietary flavonoid, on cell growth and necrosis/apoptosis and cell cycle regulation in human oral squamous carcinoma SCC-9 cells. Quercetin induced dose- and time-dependent, irreversible inhibition of cell growth and cellular DNA synthesis. Light microscopy and lactate dehydrogenase measurements showed modifications in the morphology and membrane integrity of these cells after quercetin treatment. Propidium iodide/annexin V staining showed that quercetin induced necrosis at 24 h and 48 h, whereas at 72 h cells underwent apoptosis, correlating with caspase-3 activation. Flow cytometry studies of the cell cycle distribution showed that quercetin induced mainly S-phase arrest. Thymidylate synthase (TS), a key S-phase enzyme, was inhibited in a time- and dose-dependent fashion by quercetin at the protein level. A lack of effect on TS mRNA suggested that TS down-regulation occurred at the translational level. In conclusion, our data support a view that quercetin initially induces a stress response, resulting in necrosis of these oral epithelial cells. Prolonged exposure of the surviving cells to quercetin causes apoptosis, presumably mediated by inhibition of TS protein.
 ...
PMID:Quercetin induces necrosis and apoptosis in SCC-9 oral cancer cells. 1657 83

Hepatocellular carcinoma (HCC) is the leading cause of cancer mortality in Asia. The aim of this study was to examine whether reactive oxygen species production is involved in quercetin-induced apoptosis in human HCC cell lines. Quercetin inhibited the growth of hepatoma cells in dose and time dependent manners. Quercetin treatment of hepatoma cells resulted in changes of cell cycle progression. The G0/G1phase was decreased and S phase was increased in HA22T/VGH cells after treatment with quercetin. The levels of apoptotic sub-G0/G1, reactive oxygen species and annexin V were increased prior to cell death and concurrent with lipid peroxidation in two human hepatoma cells after treatment with quercetin. Quercetin also enhanced the apoptotic effect of the chemotherapeutic agent, paclitaxel, in HA22T/VGH cells. Quercetin has therapeutic potential as an anti-cancer drug. These results provide basis for further study into the potential use of quercetin in combination with paclitaxel for treatment of hepatoma.
 ...
PMID:Reactive oxygen species production is involved in quercetin-induced apoptosis in human hepatoma cells. 1704 76

We sought to investigate the apoptosis-inducing activities of quercetin, Siamois 1, and Siamois 2 against invasive estrogen-receptor negative MDA-MB 435 cells xenografted in athymic nude mice. This study clearly demonstrated that these compounds exhibited apoptosis-inducing activities in cell culture system. Quercetin (20 microg/mL), Siamois 1 (100 microg/mL), and Siamois 2 (200 microg/mL) can induce apoptotic cell death by 40 +/-5%, 44 +/- 14 %, and 31 +/- 13 %, respectively. Two-fold of IC50 of these compounds were clearly found to induce apoptosis in breast tumor tissue which can be determined by 99mTc-Annexin V scintigraphy and histological staining. This is the first report that the apoptosis-inducing effects of quercetin, Siamois 1 and Siamois 2 on the MDA-MB 435 cell in vitro were effectively extrapolated to the in vivo situation. These compounds might be considered as a simple dietary supplement and with further clinical investigation for their use as a nutrition-based intervention in breast cancer treatment.
 ...
PMID:Quercetin, Siamois 1 and Siamois 2 induce apoptosis in human breast cancer MDA-mB-435 cells xenograft in vivo. 1722 38

Quercetin is involved in several biological activities including inhibition of cell growth and induction of apoptosis in cancer cells. However, it is unclear and unknown whether quercetin influences cell maturation. We examined the effect of quercetin on the growth and differentiation of human preadipocyte cells AML-I. Induced growth arrest of AML-I by quercetin was accompanied by the appearance of characteristics of apoptosis under the adipogenic stimulation by annexin V-fluorescein isothiocyanate staining method. A decrease of nuclear factor-kappaB and the antiapoptotic protein Mcl-1 and an increase of the proapoptotic protein Bad were observed in time-dependent fashion in the quercetin-treated cells compared with the vehicle-treated cells by Western blot analysis. Structure-related flavonoids, including rutin (quercetin-3-O-rutinoside) and quercitrin (quercetin-3-O-rhamnoside), did not have any cytotoxic effect on AML-I. Interestingly, exposure of AML-I to quercetin for 6 days increased the amount of cytoplasmic lipid droplets as well as the expression of fatty acid synthase and peroxisome proliferator-activated receptor gamma proteins. These results suggested that apoptosis induced by quercetin was not linked to adipogenic conversion of preadipocytes.
 ...
PMID:Growth arrest and apoptosis induced by quercetin is not linked to adipogenic conversion of human preadipocytes. 1799 18

Quercetin, a flavonoid found in fruits and vegetables, exerts beneficial effects that contribute to human health. Therefore, quercetin preparation is expected as complementary or alternative medicine used by general population. The plausible criterion for such medicines is to exert no toxic action on normal cells. In this study, the effects of quercetin on normal cells were examined using rat thymocytes in RPMI-1640 medium. Significant cytotoxic actions of quercetin were observed at 30 microM. Quercetin increased the populations of propidium-stained cells, shrunken cells, annexin V-positive cells, and the cells with hypodiploidal DNA. Thus, the type of cell death induced by quercetin was apoptosis. Z-VAD-FMK, a pan-inhibitor for caspases, partly attenuated the process of quercetin-induced apoptosis. It can be suggested that plasma concentration of quercetin should be below 30 microM after the digestion when quercetin preparation as complementary or alternative medicine is used.
 ...
PMID:Some characteristics of quercetin-induced cytotoxicity on rat thymocytes under in vitro condition. 1835 15

Combined treatment with quercetin and TRAIL induced cytotoxicity and enhanced annexin V staining and poly (ADP-ribose) polymerase (PARP) cleavage in human prostate cancer cell lines DU-145 and PC-3. These indicators of apoptosis resulted from the activation of caspase-8, -9, and -3. Although the expression levels of FLIPs, cIAP1, cIAP2, and the Bcl-2 family were not changed in quercetin-treated cells, significant downregulation of survivin occurred. Knockdown survivin by siRNA significantly increased TRAIL-induced apoptosis. We hypothesized that quercetin-induced activation of MAPK (ERK, p38, JNK) is responsible for downregulation of survivin gene expression. To test this hypothesis, we selectively inhibited MAPK during treatment with quercetin. Our data demonstrated that inhibitor of ERK (PD98059), but not p38 MAPK (SB203580) or JNK (SP600125), significantly maintained the intracellular level of survivin during treatment with quercetin. Interestingly, PD98059 also prevented quercetin-induced deacetylation of histone H3. Data from survivin promoter activity assay suggest that the Sp1 transcription factor binds to the survivin promoter region and quercetin inhibits its binding activity through deacetylation of histone H3. Quercetin-induced activation of the ERK-MSK1 signal transduction pathway may be responsible for deacetylation of histone H3. Taken together, our findings suggest that quercetin enhances TRAIL induced apoptosis by inhibition of survivin expression, through ERK-MSK1-mediated deacetylation of H3.
 ...
PMID:Quercetin augments TRAIL-induced apoptotic death: involvement of the ERK signal transduction pathway. 1837 72

Quercetin is known to protect the cells suffering from oxidative stress. The oxidative stress elevates intracellular Ca(2+) concentration, one of the phenomena responsible for cell death. Therefore, we hypothesized that quercetin would protect the cells suffering from overload of intracellular Ca(2+). To test the hypothesis, the effects of quercetin on the cells suffering from oxidative stress and intracellular Ca(2+) overload were examined by using a flow cytometer with appropriate fluorescence probes (propidium iodide, fluo-3-AM, and annexin V-FITC) and rat thymocytes. The concentrations (1-30 microM) of quercetin to protect the cells suffering from intracellular Ca(2+) overload by A23187, a calcium ionophore, were similar to those for the cells suffering from oxidative stress by H(2)O(2). The cell death respectively induced by H(2)O(2) and A23187 was significantly suppressed by removal of external Ca(2+). Furthermore, quercetin greatly delayed the process of Ca(2+)-dependent cell death although it did not significantly affect the elevation of intracellular Ca(2+) concentration by H(2)O(2) and A23187, respectively. It is concluded that quercetin can protect the cells from oxidative injury in spite of increased concentration of intracellular Ca(2+). Results suggest that quercetin is also used for protection of cells suffering from overload of intracellular Ca(2+).
 ...
PMID:Possible use of quercetin, an antioxidant, for protection of cells suffering from overload of intracellular Ca2+: a model experiment. 1858 79


1 2 3 4 Next >>