Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tea polyphenolic constituents induce apoptosis in cancer cells but not in normal cells. To study the mechanism of this selective effect, we used the ornithine decarboxylase (ODC)/Ras double transgenic mouse model that develops spontaneous skin tumors due to over-expression of ODC and a v-Ha-ras transgene. Administration of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) in the drinking water significantly decreased both tumor number and total tumor burden compared with untreated ODC/Ras mice without decreasing the elevated polyamine levels present in the ODC/Ras mice. EGCG selectively decreased both proliferation and survival of primary cultures of ODC over-expressing transgenic keratinocytes but not keratinocytes from normal littermates nor ras-infected keratinocytes. This decreased survival was due to EGCG-induced apoptosis and not terminal differentiation. Moreover, in skin from EGCG-treated ODC transgenic mice, caspase 3 (active form) was detected only in epidermal cells that possess very high levels of ODC protein. Since most transformed cells and tumor tissue possess higher levels of polyamines compared with normal cells or tissue, our data suggest that the elevated levels of polyamines in tumor cells sensitize them to EGCG-induced apoptosis. These results suggest that EGCG may be an effective chemopreventive agent in individuals with early, pre-neoplastic stages of cancer having higher levels of polyamines.
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PMID:Elevated polyamines lead to selective induction of apoptosis and inhibition of tumorigenesis by (-)-epigallocatechin-3-gallate (EGCG) in ODC/Ras transgenic mice. 1537 10

The cultivated mycelium of a Cordyceps sinensis (Cs) fungus was sequentially extracted by petroleum ether, ethyl acetate (EtOAc), ethanol and water. The EtOAc extract showed the most potent cytotoxic effect against the proliferation of human premyelocytic leukemia cell HL-60, with an ED50 < or = 25 microg/ml for 2-day treatment. The EtOAc extract induced the characteristic apoptotic symptoms in the HL-60 cells, DNA fragmentation and chromatin condensation, occurring within 6-8 h of treatment at a dose of 200 microg/ml. The activation of caspase-3 and the specific proteolytic cleavage of poly ADP-ribose polymerase were detected during the course of apoptosis induction. These results suggest that the Cs mycelium extract inhibited the cancer cell proliferation by inducing cell apoptosis.
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PMID:Induction of HL-60 apoptosis by ethyl acetate extract of Cordyceps sinensis fungal mycelium. 1545 42

Studies in cell culture and laboratory animals have shown that green tea and its major component, epigallocatechin-3-gallate, inhibit cell growth and reduce tumor incidence. However, results of epidemiological studies have generated inconsistent, sometimes conflicting data regarding protection by green tea against human cancers. To clarify the findings of these laboratory studies in application to humans, we conducted a pilot intervention study with three heavy smokers (> 10 cigarettes/day) and three nonsmokers (never smokers) in order to evaluate the molecular and cellular effects of drinking green tea using human oral cells as an investigative tool. Green tea total extract (400-500 mg/cup, 5 cups/day) was administered in drinking water to the subjects for four weeks. Two oral cytology samples were taken weekly for measurements of tobacco carcinogen-induced DNA damage, including bulky adducts and oxidized bases, cell growth, DNA content, and apoptosis. The study showed that during the course of green tea administration smoking-induced DNA damage was decreased, cell growth was inhibited, and the percentage of cells in S phase was reduced, cells accumulated in G1 phase (cyclin D1 positive), DNA content became more diploid and less aneuploid, and p53, Caspase-3, and TUNEL, markers of apoptosis, were increased. The study, although preliminary, indicates that drinking green tea reduced the number of damaged cells in smokers by inducing cell growth arrest and apoptosis, a mechanism similar to that observed in cultured cells and animals. These results warrant a large-scale intervention trial to further verify the role of green tea in the prevention of oral cancer in smokers.
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PMID:Molecular and cellular effects of green tea on oral cells of smokers: a pilot study. 1553 15

The cells of the kidney medulla are exposed routinely to high extracellular concentrations of various solutes including NaCl, urea and ammonium (NH4+). Although it is well established that the expression of a variety of osmosensitive genes and proteins, which confer cytoprotection on renal medullary cells, is induced by high NaCl concentrations, the role of NH4+ in these cellular responses is unclear. This study thus addressed the effect of NH4+ on the expression of the betaine/GABA transporter (BGT-1), the sodium/myo-inositol cotransporter (SMIT), aldose reductase (AR), and heat shock protein 70 (HSP70) in Madin-Darby canine kidney (MDCK) cells, using Northern and Western blot analyses and enzyme-linked immunosorbent assay (ELISA). The incidence of apoptosis was monitored by determining caspase-3 activity and annexin V binding. Addition of NH4Cl (50 mM; total osmolality 400 mosmol (kg H2O)(-1) to the medium was more effective than equiosmolar NaCl in increasing BGT-1 and HSP70 mRNA abundance, but less effective in enhancing BGT-1 and HSP70 expression at the protein level. Qualitatively similar results were obtained for SMIT and AR mRNAs. Exposure to both isotonic and hypertonic, NH4Cl-containing medium enhanced apoptosis compared with equiosmolar, NaCl-containing media. These results suggest that, in addition to NaCl, NH4Cl may play a role in regulating the intracellular accumulation of organic osmolytes, the abundance of HSP70 and cell turnover in the renal medulla in vivo.
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PMID:Effect of ammonium on the expression of osmosensitive genes in Madin-Darby canine kidney cells. 1561 70

Gagam-whanglyun-haedoktang (GWH) is a newly designed herbal drug formula based on the traditional oriental pharmacological knowledge for the purpose of treating tumorous diseases. Apoptosis is an evolutionarily conserved suicide program residing in cells. In the present study, apoptosis inducing activities of the decocted water extract of GWH were studied. Results of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that GWH had a strong cytotoxic effect on HL-60 cells. The number of live cells was less than 20% after exposure to 1 mg/ml GWH for 48 h. GWH increased cytotoxicity of HL-60 cells in a dose- and time-dependent manner. The percentage of apoptotic cells by flow cytometric analysis of the DNA-stained cells increased to 28%, 31%, and 37% at 24 h and to 37%, 44%, and 81% at 48 h after treatment with 0.01, 0.1, and 1 mg/ml GWH, respectively. DNA fragmentation also occurred in apoptosis and was characterized by a ladder pattern on agarose gel. In addition, GWH increased the secretion of tumor necrosis factor-alpha. GWH-induced apoptosis was accompanied by activation of caspase-3. These results suggest that GWH induces activation of caspase-3 and eventually leads to apoptosis.
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PMID:Induction of apoptosis by Korean medicine Gagam-whanglyun-haedoktang through activation of caspase-3 in human leukemia cell line, HL-60 cells. 1565 86

Oxysterols have been shown to induce apoptosis in a variety of cell lines. The mechanism of oxysterol-induced apoptosis is mainly known at the post-mitochondrial level. The aim of the present study was to compare the pathway of apoptosis induced by the oxysterols 7beta-hydroxycholesterol (7beta-OH) and cholesterol-5beta,6beta-epoxide (beta-epoxide) in U937 cells. To this end, we employed a range of inhibitors of apoptosis; a broad-spectrum caspase inhibitor, a specific caspase-3 inhibitor and an inhibitor of cytochrome c release and the antioxidants; trolox, ebselen and resveratrol. The three inhibitors of apoptosis prevented cell death induced by 7beta-OH; however, in beta-epoxide-treated cells, the inhibitor of cytochrome c release did not protect against apoptosis. The cellular antioxidant glutathione was depleted in 7beta-OH-treated cells but not in cells incubated with beta-epoxide. Trolox, a water-soluble synthetic analogue of alpha-tocopherol, prevented 7beta-OH-induced apoptosis but did not protect against cell death induced by beta-epoxide. Ebselen and resveratrol did not protect U937 cells against apoptosis induced by either 7beta-OH or beta-epoxide. Our results suggest that differences occur in the pathways of apoptosis induced by 7beta-OH and beta-epoxide in U937 cells.
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PMID:Comparison of the apoptotic processes induced by the oxysterols 7beta-hydroxycholesterol and cholesterol-5beta,6beta-epoxide. 1568 34

Pollutant particles induce apoptosis and inflammation, but the relationship between these two biological processes is not entirely clear. In this study, we compared the proapoptotic and proinflammatory effects of four particles: residual oil fly ash (ROFA), St. Louis particles SRM 1648 (SL), Chapel Hill PM10 (CHP), and Mount St. Helens dust (MSH). Human alveolar macrophages (AM) were incubated with these particles at 100 microg/ml. Cell death was assessed by annexin V (AV) expression, histone release, nuclear morphology, caspase 3-like activity and release of caspase 1 for apoptosis, and propidium iodide (PI) for necrosis, and inflammation was measured by interleukin (IL)-1beta and IL-6. We found that particle effects on these cell death measurements varied, and ROFA affected most (four out of five) endpoints, including nuclear morphological changes. CHP and SL also caused necrosis. For cytokine release, the potency was CHP > SL > ROFA > MSH. The proapoptotic and proinflammatory effects induced by the whole particles were unaltered after the particles were washed with water. The water-soluble fraction was relatively inactive, as were individual soluble metals (V, Ni, Fe). ROFA-induced nuclear fragmentation was associated with upregulation and mitochondrial release of apoptosis-inducing factor (AIF), a caspase-independent chromatin condensation factor, and upregulation of DNase II, a lysosomal acid endonuclease. These results indicate that the potential for particles to induce apoptosis does not correlate with their proinflammatory properties, although active components for both processes reside in the water-insoluble core. Both apoptosis and inflammatory endpoints should be included when the toxicity of different pollutant particles is assessed.
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PMID:Apoptotic and inflammatory effects induced by different particles in human alveolar macrophages. 1576 74

Neonatal hypoxic-ischemic brain injury remains a significant cause of morbidity and mortality and lacks effective therapies for prevention and treatment. Recently, interest in the biology of polyphenol compounds has led to the discovery that dietary supplementation with foods rich in polyphenols (e.g. blueberries, green tea extract) provides neuroprotection in adult animal models of ischemia and Alzheimer's disease. We sought to determine whether protection of the neonatal brain against a hypoxic-ischemic insult could be attained through supplementation of the maternal diet with pomegranate juice, notable for its high polyphenol content. Mouse dams were provided ad libitum access to drinking water with pomegranate juice, at one of three doses, as well as plain water, sugar water, and vitamin C water controls during the last third of pregnancy and throughout the duration of litter suckling. At postnatal day 7, pups underwent unilateral carotid ligation followed by exposure to 8% oxygen for 45 min. Brain injury was assessed histologically after 1 wk (percentage of tissue area loss) and biochemically after 24 h (caspase-3 activity). Dietary supplementation with pomegranate juice resulted in markedly decreased brain tissue loss (>60%) in all three brain regions assessed, with the highest pomegranate juice dose having greatest significance (p < or = 0.0001). Pomegranate juice also diminished caspase-3 activation by 84% in the hippocampus and 64% in the cortex. Ellagic acid, a polyphenolic component in pomegranate juice, was detected in plasma from treated but not control pups. These results demonstrate that maternal dietary supplementation with pomegranate juice is neuroprotective for the neonatal brain.
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PMID:Maternal dietary supplementation with pomegranate juice is neuroprotective in an animal model of neonatal hypoxic-ischemic brain injury. 1577 34

Apples contain several classes of polyphenols: monomers (catechins, epicatechins) and oligomers/polymers, such as the procyanidins. Our aim was (i) to study anti-proliferative mechanisms on human metastatic colon carcinoma (SW620 cells) of apple polyphenol fractions (monomers or procyanidins) and (ii) to evaluate their anti-carcinogenic properties in vivo. Two polyphenol-enriched fractions were isolated from apples. Fraction non-procyanidins contained 73% phenolic monomers and no procyanidins, while fraction procyanidins contained 78% procyanidins and no monomers. Inhibition of SW620 cell growth was only observed with fraction P (IC50 = 45 microg/ml). After a 24-h exposure of cells to fraction P, protein kinase C activity was inhibited by 70% and a significant increase in extracellular signal-regulated kinases 1 and 2 and c-jun N-terminal kinases expression was observed together with the down-regulation of polyamine biosynthesis and the activation of caspase-3. Colon carcinogenesis was induced in rats by intraperitoneal injections of azoxymethane, once a week for 2 weeks. Seven days after the last injection, Wistar rats received fraction P (0.01%) dissolved in drinking water. After 6 weeks of treatment, the colon of rats receiving procyanidins showed a significant (P < 0.01) reduction of the number of preneoplastic lesions when compared with controls receiving water. The total number of hyperproliferative crypts and of aberrant crypt foci was reduced by 50% in rats receiving 0.01% apple procyanidins in their drinking water. Our results show that apple procyanidins alter intracellular signaling pathways, polyamine biosynthesis and trigger apoptosis in tumor cells. These compounds antagonize cancer promotion in vivo. In contrast with absorbable drugs, these natural, non toxic, dietary constituents reach the colon where they are able to exert their antitumor effects.
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PMID:Chemopreventive properties of apple procyanidins on human colon cancer-derived metastatic SW620 cells and in a rat model of colon carcinogenesis. 1579 May 89

Fluorine compounds are widely used for the prevention of caries, and recently sodium fluorosilicate has been used in water fluorination. The cytotoxic effects of sodium fluorosilicate in several osteosarcoma and oral cancer cells were evaluated in this study by measurement of inhibition of cell proliferation. Human osteogenic sarcoma (HOS) cells were the most sensitive to sodium fluorosilicate treatment. Induction of apoptosis, such as nucleosomal DNA fragmentation and the appearance of apoptotic bodies, were observed in HOS cells by agarose gel electrophoresis and by flow cytometric analysis, respectively. The molecular mechanism of apoptosis induction in HOS was investigated by Western blot analysis. The level of Bcl-2 was decreased and consequent release of cytochrome c was increased. Caspase-3 was activated and the cleavage of poly (ADP-ribosyl) polymerase was increased. In conclusion, sodium fluorosilicate induces apoptosis in HOS cells through decrease in Bcl-2, the release of cytochrome c to the cytosol and activation of caspase-3.
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PMID:Induction of apoptosis by sodium fluorosilicate treatment in human osteogenic sarcoma (HOS) cells. 1581 63


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