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)

The effects of insulin-like growth factor-1 (IGF-1) on the cytotoxicity and apoptosis induced by okadaic acid (OA) in SH-SY5Y cells were investigated. Cell viability was measured using the MTT (3-(4,5-dimethylthiazolyl-2)-2,-5-diphenyltetrazolium bromide) assay. Early and late apoptosis/necrosis were analyzed by flow cytometry using Annexin V and propidium iodide (PI) double-staining. Caspase-3 activation was detected by Western blot analysis. Preincubation with IGF-1 for 24 h prevented cytotoxicity induced by 40 nM OA given for 24 h, and the MTT value significantly increased. Incubation with 20 nM OA for 24 h caused a marked increase in the percentage of early apoptotic and late apoptotic/necrotic cells, which was not dependent on the activation of caspase-3. OA-induced apoptosis was significantly decreased by pretreatment with 10 ng/ml of IGF-1 for 24 h. The results supported the hypothesis that IGF-1 may be useful in the treatment of Alzheimer's disease.
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PMID:Effects of insulin-like growth factor-1 on okadaic acid-induced apoptosis in SH-SY5Y cells. 1608 62

The purpose of this study was to investigate the cytotoxicity of iontophoresis treatment using direct current (DC) with or without antibacterial agents. The following antibacterial agents were used: diamine silver fluoride (AgF); sodium fluoride (NaF); and iodine zinc iodide (JJZ). The cytotoxic activity of DC with or without antibacterial agents against human polymorphonuclear cells (PMNs) was evaluated by the 3-[4, 5- dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. It was noted that DC (2 mA) killed PMNs in a time-dependent manner and the cytotoxicity was enhanced when DC was combined with antibacterial agents. The toxic effect of antibacterial agents was in the order: AgF>JJZ>NaF. The death of PMNs by DC was evaluated by flow cytometry using annexin V-FITC/propidium iodide staining. DC appeared to induce necrosis rather than apoptosis of PMNs. These results suggest that iontophoresis treatment using DC and antibacterial agents may induce necrotic cytotoxicity in host cells around periapical lesions.
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PMID:Cytotoxicity of direct current with antibacterial agents against host cells in vitro. 1618 58

Cancer disease is a major cause of death in Western societies. Epidemiologically, antioxidant phenols have been associated with diminished incidence of cancer, while experimentally, they have cytotoxic effects on cancer cells. The aim of this study was to clarify whether natural antioxidant phenols render K562 human leukemic cells more susceptible to natural killer (NK) cell apoptosis and/or necrosis. K562 cells were pre-incubated with 7 different phenols (p-hydroxy benzoic acid, syringic acid, ferulic acid, p-coumaric acid, o-coumaric acid, gallic acid, and rutin) individually and afterwards targeted with NK cells at a ratio 1/5. Percentages of apoptotic and necrotic cells were assayed via flow cytometric analysis of annexin V and PI-stained cells. For the morphological assessment, cells were stained with acridine orange and ethidium bromide and were examined under a fluorescence microscope. Pre-treatment with gallic acid significantly rendered K562 cells more susceptible to NK cell-mediated necrosis, while pre-treatment with rutin significantly rendered K562 cells more susceptible to apoptosis. Gallic acid and rutin exert anticarcinogenic activity via the enhancement of K562 cell susceptibility to NK cell-mediated necrosis and apoptosis, respectively.
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PMID:Effect of phenols on natural killer (NK) cell-mediated death in the K562 human leukemic cell line. 1619 4

Previous investigations have shown that 2-hydroxyethyl methacrylate (HEMA) causes reactive oxygen species (ROS) production, which in turn affects cell survival and cell death. The purpose of this study was to evaluate the effects of the antioxidant N-acetyl-L-cysteine (NAC) on HEMA-induced toxicity in human primary gingival fibroblasts (HGF). HGF were treated with various concentrations of HEMA (0-12 mm) in the absence and presence of NAC (1, 5, and 10 mm). The 3-(4,5 dimethyiazol-2-1)-2-5-diphenyl tetrazolium bromide (MTT) assay was used to evaluate the mitochondrial dehydrogenase activity after HEMA exposure. Viability and cell death were determined by flow cytometry using Annexin V and PI staining. ROS production was detected by the increasing fluorescence of the oxidation-sensitive dye 2',7'-dichlorofluorescein diacetate (DCFH-DA) after HEMA treatment. After a 24h incubation period, HEMA concentrations higher then 10mm caused a decrease of cell viability, mitochondrial activity, and an increase of cell death. HEMA concentrations of 4-12 mm markedly increased ROS levels in a dose-dependent manner. High NAC concentrations (5 and 10 mm) significantly reduced cell death, and restored the mitochondrial activity after a 24 h co-treatment, but 1 mm NAC increased HEMA toxicity (p<0.05). All NAC concentrations significantly reduced ROS levels induced by HEMA after a 2 h exposure (p<0.05), but no such reduction was observed after a 4 h treatment. Furthermore, treatment with 10 mm HEMA and 1 mm NAC for 6h caused an increase in ROS levels compared to 10 mm HEMA alone (p<0.05). In conclusion, our results suggest that high NAC concentrations protect HGF against HEMA cytotoxicity by reducing the induced ROS levels.
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PMID:Effect of N-acetyl-L-cysteine on ROS production and cell death caused by HEMA in human primary gingival fibroblasts. 1628 59

Histone deacetylase inhibitors (HDACIs) can inhibit cell proliferation, induce cell cycle arrest, and stimulate the apoptosis of cancer cells. We investigated the effects of a novel HDACI, Scriptaid, on the Ishikawa endometrial cancer cell line, SK-OV-3 ovarian cancer cell line, and normal human endometrial epithelial cells. Endometrial and ovarian cancer cells were treated with various concentrations of Scriptaid, and its effect on cell growth, cell cycle, apoptosis, and related measurements was investigated. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed that all endometrial and ovarian cancer cell lines were sensitive to the growth inhibitory effect of Scriptaid, although normal endometrial epithelial cells were viable after treatment with the same doses of Scriptaid that induced the growth inhibition of endometrial and ovarian cancer cells. Cell cycle analysis indicated that their exposure to Scriptaid decreased the proportion of cells in the S phase and increased the proportion in the G0/G1 and/or G2/M phases of the cell cycle. Induction of apoptosis was confirmed by annexin V staining of externalized phosphatidylserine and loss of the transmembrane potential of mitochondria. This induction occurred in concert with the altered expression of genes related to cell growth, malignant phenotype, and apoptosis. Furthermore, Scriptaid treatment of these cell lines increased acetylation of H3 and H4 histone tails. These results raise the possibility that Scriptaid may prove particularly effective in the treatment of endometrial and ovarian cancers.
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PMID:A novel histone deacetylase inhibitor, Scriptaid, induces growth inhibition, cell cycle arrest and apoptosis in human endometrial cancer and ovarian cancer cells. 1639 33

Arecoline, the main areca alkaloid in betel quid (BQ), is reported to have cytotoxic, genotoxic, and mutagenic effects in various cells. It shows strong correlation to the incidence of oral submucous fibrosis, leukoplakia, and oral cancer. To clarify the role of arecoline in BQ-induced carcinogenesis, primary human gingival keratinocyes (GK) and human KB epithelial cells were used for studying the molecular mechanisms of arecoline-mediated cell cycle deregulation for comparison. After 24 h of exposure, arecoline (0.2-0.8 mM) inhibited KB cell growth in a dose- and time-dependent manner with a reduction in cell number by 27-37 and 37-58%, respectively, as determined by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. Incubation of KB cells with arecoline (0.1-0.4 mM) caused late-S and G2/M phases' cell cycle arrest. Western blot analysis revealed that arecoline induced cyclin Bl, Wee 1, and phosphorylated cdc2 protein levels whereas it declined p21 protein expression in KB cancer cells. Nevertheless, arecoline induced p21, but decreased cdc2 and cyclin B1 protein levels in GK. We demonstrated that higher concentrations of arecoline (0.2-1.2 mM) induced both cell necrosis and apoptosis as detected by DNA fragmentation and Annexin V-PI staining after long-term (48 h) treatment. Our results suggest that differential regulation of S and/or G2/M cell cycle-related proteins in the GK and KB cells play a crucial role in different stages of BQ-mediated carcinogenesis.
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PMID:Prolonged exposure to arecoline arrested human KB epithelial cell growth: regulatory mechanisms of cell cycle and apoptosis. 1641 51

Arsenic trioxide (As2O3) has recently been used to treat acute promyelocytic leukaemia and has activity in vitro against several solid tumour cell lines where the induction of differentiation and apoptosis are the prime effects. The mechanism of As2O3-induced cell death has yet to be clarified, especially in solid cancers. In the present study, the human breast cancer cell line MCF-7 was examined as a cellular model for As2O3 treatment. The involvement of extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK) was investigated in As2O3-induced cell death. 3. It was found that As2O3 activates the prosurvival mitogen-activated protein kinase kinase (MEK)/ERK pathway in MCF-7 cells, which, conversely, may compromise the efficacy of As2O3. Hence, a combination treatment of As2O3 and MEK inhibitors was investigated to determine whether this treatment could lead to enhanced growth inhibition and apoptosis in MCF-7 cells. 4. Inhibition of MEK/ERK with the pharmacological inhibitors U0126 (10 micromol/L) or PD98059 (20 micromol/L) together with As2O3 (2 and 5 micromol/L) resulted in a significant enhancement of growth inhibition in breast cancer MCF-7 cells as determined by the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay and [Methyl-3H]-thymidine incorporation. Furthermore, the results demonstrated that combined treatment with As2O3 and the MEK1/2 inhibitor U0126 could augment breast cancer MCF-7 cell apoptosis approximately twofold compared with the effects of the two drugs alone, as determined by Hoechst 33258 or annexin V/propidium iodide (PI) staining and flow cytometry. 5. In addition, As2O3 activated p38 in a dose-dependent manner, but had no effect on JNK1/2. Treatment with a p38 inhibitor did not prevent As2O3-induced apoptosis. 6. In conclusion, the results of the present study showed that enhanced apoptosis is detected in breast cancer MCF-7 cells in the presence of As2O3 and an MEK inhibitor, which may be a new promising adjuvant to current breast cancer treatments.
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PMID:Inhibition of mitogen-activated protein kinase kinase enhances apoptosis induced by arsenic trioxide in human breast cancer MCF-7 cells. 1644 69

Resveratrol has been proposed to act as a chemopreventive agent in numerous epidemiologic studies and has been shown to inhibit proliferation of various tumor cells in vitro. In the present study, we investigated the antitumor effects of resveratrol on multiple myeloma (MM) cells and the mechanisms involved. Our findings indicated that resveratrol inhibited proliferation of tumor cells in a dose- [corrected] dependent manner by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and [3H]thymidine incorporation assay. Resveratrol also enhanced the inhibitory effect of dexamethasone on the growth of MM cells by MTT assay. Flow cytometric analysis demonstrated that resveratrol arrested the cells at the G1 and S phases of the cell cycle. Because nuclear factor-kappaB (NF-kappaB) plays a key role in cell survival and proliferation of human MM cells, we tested the effect of resveratrol on NF-kappaB expression by Western blot analysis and immunofluorescence. NF-kappaB was constitutively active in all human MM cell lines examined, and resveratrol down-regulated NF-kappaB expression in all cell lines. Resveratrol also down-regulated the expression of NF-kappaB-regulated gene products by Western blot analysis, gelatin zymography, and enzyme-linked immunosorbent assay, including interleukin-6, Bcl-2, Bcl-xL, XIAP, c-IAP, vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9), which modulates an array of signals controlling cellular survival and proliferation and tumor promotion. Indeed, annexin V-fluoroisothyocyanate and Transwell invasion analyses revealed that incubation of MM cells with resveratrol resulted in apoptotic cell death and inhibition of invasion. In conclusion, these data suggest that resveratrol is an effective in vitro inhibitor of NF-kappaB in human MM cells. Resveratrol plays a role in suppressing the proliferation of MM cells and induces apoptosis, thus providing the molecular basis for the treatment of MM patients with this compound.
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PMID:Resveratrol downregulates the constitutional activation of nuclear factor-kappaB in multiple myeloma cells, leading to suppression of proliferation and invasion, arrest of cell cycle, and induction of apoptosis. 1649 May 92

The study was aimed to investigate the expression of Rac1 in human acute leukemic cell line HL-60 and effect of Rac1 on cell cycle progression and apoptosis. The mRNA expression of Rac1 in HL-60 cell line and normal human peripheral blood mononuclear cells (PBMNC) were examined by semi-quantitative RT-PCR. After transfection of HL-60 cells with different concentrations of Rac1 antisense oligodeoxynucleotide (ASODN) by means of FuGENE6, the survival, cell cycle, apoptosis of HL-60 cells were observed through MTT assay, FCM test, Wright-Giemsa, acridine orange/ethidium bromide (AO/EB) and Annexin V-FITC/PI staining test respectively. The results showed that Rac1 relative amount in HL-60 was 0.84 +/- 0.13, while it in the normal PBMNC was 0.26 +/- 0.1 (P < 0.01); the expression of Rac1 in HL-60 cells was significantly upregulated. Compared with sense oligodeoxynucleotide (SODN), HL-60 cell viability, after exposure to ASODN at a concentration of 2.0 g/L decreased, (73.7 +/- 5.0)% vs (93.2 +/- 3.0)% (P < 0.01), while the proportion of G(1) cells increased as (52.1 +/- 6.8)% vs (31.6 +/- 4.7)% (P < 0.05), the percentage of Annexin V positive cells increased, (19.2 +/- 2.1)% vs (4.1 +/- 1.7)% (P < 0.01), and HL-60 cells were observed to have formation of apoptotic bodies. The data presented indicate that Rac1 may be involved in regulation of HL-60 cell cycle and apoptosis, promote overproliferation of HL-60 cells and inhibit their apoptosis.
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PMID:[Rac1 expression and its effects on the cell cycle progression and apoptosis in human acute leukemic cell line HL-60]. 1658 82

Physiological roles of microsomal (iPLA(2)gamma) and cytosolic (iPLA(2)beta)Ca(2+)-independent phospholipase A(2) were determined in two different epithelial cell models. R- and S-enantiomers of the iPLA(2) inhibitor bromoenol lactone (BEL) were isolated and shown to selectively inhibit iPLA(2gamma) and iPLA(2beta), respectively. The effect of these enantiomers on cell growth was assessed in human embryonic kidney 293 and Caki-1 cells using 3-(4-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT). S-BEL (0-5.0 microM) decreased MTT staining 35% after 24 h compared with control cells, whereas treatment with either R-BEL or R/S-BEL induced 15% decreases. Neither R-BEL nor S-BEL induced cell death as determined by annexin V and propidium iodide staining. Transfection of cells with iPLA(2)beta siRNA reduced MTT staining approximately 35%, whereas transfection of cells with iPLA(2)gamma siRNA only decreased MTT staining 10 to 15% compared with control cells. The effect of iPLA(2)beta and iPLA(2)gamma siRNA on cell number and protein was also determined, and iPLA(2)beta siRNA decreased cell number and protein 25% compared with control cells. In contrast, iPLA(2)gamma siRNA decreased cell number, but not cellular protein, compared with control cells. Selective inhibition of iPLA(2)beta, but not iPLA(2)gamma, decreased several arachidonic acid-containing phospholipids, including 16:1-20:4, 16:0-20:4, 18:1-20:4, and 18:0-20:4 phosphatidylcholine, showing that the ability of iPLA(2)beta inhibitors to decrease cell growth correlates with their ability to decrease arachidonic acid-containing phospholipids. These data show that iPLA(2)beta inhibition results in greater decreases in cell growth and proliferation than iPLA(2)gamma, identifies specific phospholipids whose expressions are differentially regulated by iPLA(2)beta and iPLA(2)gamma, and suggests novel roles for iPLA(2)beta in cell growth.
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PMID:Differential roles for cytosolic and microsomal Ca2+-independent phospholipase A2 in cell growth and maintenance of phospholipids. 1676 94


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