Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chan Su is a traditional Chinese medicine prepared from the dried white secretion of the auricular and skin glands of toads, and has been used as an Oriental drug. However, little is known about the effect of Chan Su on the growth of human cancer cells. This study was undertaken to investigate the underlying mechanism of Chan Su-induced apoptosis in a human bladder carcinoma cell line, T24. The effects of this compound were also tested on cyclooxygenase (COX) activity. Treatment of T24 cells with Chan Su resulted in the inhibition of viability and induction of apoptosis in a concentration-dependent manner, which was proved by trypan blue counts, DAPI staining, agarose gel electrophoresis and flow cytometric analysis. Apoptosis of T24 cells by Chan Su was associated with a down-regulation of anti-apoptotic Bcl-2 and Bcl-X(S/L) expression and an up-regulation of pro-apoptotic Bax expression. Chan Su treatment induced the proteolytic activation of caspase-3 and caspase-9, and a concomitant degradation of poly(ADP-ribose)-polymerase and beta-catenin protein. Furthermore, Chan Su decreased the levels of COX-2 mRNA and protein expression without significant changes in the levels of COX-1, which was correlated with an inhibition in prostaglandin E(2) synthesis. Taken together, these findings partially provide novel insights into the possible molecular mechanisms of the anti-cancer activity of Chan Su.
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PMID:Induction of apoptosis by Chan Su, a traditional Chinese medicine, in human bladder carcinoma T24 cells. 1601 33

Bcl-2 is best known for its anti-apoptotic function in a wide variety of cell types. The objective of this study was to investigate the effects of bcl-2 on the types of cell demise in the HeLa/bcl-2 cells induced by H2O2. The HeLa cell expressed stably bcl-2 was established and defined as the HeLa/bcl-2 cell strain, while the cell transfected with the empty expression vector was defined as the HeLa/vector cell strain. MTT assay revealed that the HeLa/bcl-2 cells showed a shorter life span. BrdU incorporation assay indicated that the bcl-2 exerted anti-demise effect on the HeLa/bcl-2 cells at the low concentration of H2O2. However, at the high concentration of H2O2, the death of the HeLa/bcl-2 cells was more than that of the HeLa/vector cells. The flow cytometry demonstrated that H2O2 mainly induced apoptosis in the HeLa/vector cells and elicited necrosis in the HeLa/bcl-2 cells. The addition of celecoxib to the cells treated by H2O2 could increase apoptosis in the HeLa/vector cells and convert necrosis into apoptosis in the HeLa/bcl-2 cells. The higher levels of cellular free radical and GSH were found in the HeLa/bcl-2 cells, but not in the HeLa/vector cells. With 200 microM H2O2 challenge for 48 h, the level of the cellular free radical was increased in the both strains, while the level of the GSH was decreased in the both strains. Celecoxib could reverse the difference between the both strains led by H2O2. Western blotting showed that the expression of COX-2 was always higher in the HeLa/bcl-2 cells than in the HeLa/vector cells under the both of treated and untreated with H2O2, while the level of COX-1 was relative stable in the both strains. These results suggested that the crosstalk between the bcl-2 and the COX-2 pathways could exist, the bcl-2 might up-regulate COX-2 to modify sensitivity to the types of demise in the HeLa/bcl-2 cell.
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PMID:Bcl-2 switches the type of demise from apoptosis to necrosis via cyclooxygenase-2 upregulation in HeLa cell induced by hydrogen peroxide. 1645 14

The objective of the present study was to determine the influence of cyclooxygenase-2 (COX-2) inhibition by Celecoxib (CLX) in humans with distal colorectal adenocarcinoma (CRC) on serum and tumor levels of progastrin and gastrin and serum levels of proinflammatory cytokines (IL-8, TNF-alpha). In addition, the effects of this CLX treatment on tumor and adjacent mucosa expression of gastrin, its receptors (CCK2), and COX-1 and COX-2, as well as protein expression of the active form of nuclear factor kappa B (NFkappa B) and the apoptotic-related proteins Bcl-2 and survivin, have been examined. Ten distal CRC patients were examined twice, once before and then after 14-day treatment with CLX (200 mg bid). Large biopsy samples were taken from the tumor and intact mucosa 10 cm above the tumor. For comparison, 20 age- and sex-matched healthy controls were enrolled and treated with CLX as CRC patients. Serum levels of IL-8 and TNF-alpha were measured by enzyme-linked immunosorbent assay, and serum levels of amidated gastrins and progastrin, by specific radioimmunoassay. The gene or protein expressions of progastrin, gastrin, CCK2, COX-1, COX-2, Bcl-2, and survivin as well as NFkappa B were determined by RT-PCR or Western blot in biopsy samples of tumor and intact mucosa of CRC patients. Serum IL-8 and TNF-alpha values were severalfold higher in CRC patients than in controls. The increase in serum proinflammatory cytokines was accompanied by increased expression of the active form of NFkappa B. Serum progastrin levels were also found to be significantly higher in CRC than in controls. Treatment of CRC with CLX resulted in a significant decrease in serum levels of progastrin and this was accompanied by an increment in tumor expression of COX-2 with a concomitant reduction in gastrin, Bcl-2, survivin, and NFkappa B expression. We conclude that (1) distal CRC patients show significantly higher serum progastrin levels than matched healthy controls, confirming that this hormone may be implicated in rectal carcinogenesis; (2) CRC patients exhibit significantly higher serum levels of IL-8 and TNF-alpha than healthy controls, probably reflecting more widespread inflammatory reaction in the colonic mucosa in CRC; (3) gastrin, COX-2, Bcl-2, survivin, and NFkappa B were overexpressed in CRC tumor compared to intact mucosa, but treatment with CLX significantly reduced serum levels of progastrin and IL-8 and TNF-alpha, which could mediate the up-regulation of COX-2 in CRC; and (4) CLX also enhanced expression of COX-2, while inhibiting the expression of gastrin, Bcl-2, survivin, and NFkappa B, suggesting that COX-2 inhibition might be useful in chemoprevention against CRC, possibly due to suppression of the antiapoptotic proteins and reduction in progastrin-induced and NFkappa B-promoted tumor growth.
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PMID:Effects of cyclooxygenase-2 inhibition on serum and tumor gastrins and expression of apoptosis-related proteins in colorectal cancer. 1661 3

SC-1, the aqueous phase of soybean fermentation products by bacteria (Bacillus subtilis and Bacillus brevis), significantly inhibited the growth and clonogenesity of human hepatocellular (Hep 3B), mouse hepatocellular (ML-1), and human colorectal (HCT 116 and HT-29) carcinoma cells. Cytotoxicity of SC-1 in Hep 3B cells was through the process of apoptosis characterizing by increase in cell population of sub-G(1) phase, fragmentation of DNA, and change of nuclear morphology. Treatment of Hep 3B cells with SC-1 activated caspase 8 and caspase 3. Elevation of nuclear DNA fragmentation factor 40 (DFF40) and cleavage form of poly(ADP-ribose) polymerase (PARP) were also observed. SC-1 also activated intrinsic pathway via increase of pro-apoptotic (tBid, Bak and Bax) and decrease of anti-apoptotic (Bcl-2 and Bcl-x(L)) proteins on mitochondria, disruption of mitochondrial membrane potential, release of cytochrome c and Smac (second mitochondria-derived activator of caspase/direct IAP binding protein with low PI) from mitochondria, and activation of caspase 9. Inhibition on protein expression of Ku70 in cytosol and cyclooxygenase (COX)-2, but not COX-1, in whole cell lystes were revealed in SC-1-treated Hep 3B cells. These results suggest caspase 8, Ku70 and mitochondria are involved in the antitumor mechanism of SC-1 in Hep 3B cells.
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PMID:Supernatant of bacterial fermented soybean induces apoptosis of human hepatocellular carcinoma Hep 3B cells via activation of caspase 8 and mitochondria. 1703 Mar 78

This study was performed to evaluate whether down-regulation of prostaglandin E(2) (PGE(2)) synthesis by celecoxib treatment is associated with inhibition of cell growth in human colon carcinoma cell lines. Physiologic concentrations of celecoxib (5-10 microM) inhibited 80% to 90% of PGE(2) production in HT-29 cells that express high levels of COX-2 protein. In these concentrations, celecoxib had a minor inhibitory effect (20-30%) on cell growth. There was a significant change in induction of apoptosis only at higher concentrations of celecoxib (>20 microM). Treatment by low concentrations of celecoxib did not alter the levels of COX-1, beta-catenin, P(27), Bcl-2, and Bcl-x proteins. The effect of celecoxib on cell growth inhibition was higher on the COX-2-positive HT-29 cell line (IC(50)=20 microM) than on the COX-2 deficient SW-480 cell line (IC(50)=35 microM). In conclusion, inhibition of PGE(2) synthesis is an early, but not sufficient, step in the mechanism of celecoxib-mediated cell growth inhibition. These results support the need for additional evaluation of independent COX-2 pathways of celecoxib in chemoprevention of CRC.
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PMID:Down-regulation of PGE2 by physiologic levels of celecoxib is not sufficient to induce apoptosis or inhibit cell proliferation in human colon carcinoma cell lines. 1734 86

Rheumatoid arthritis (RA) is a chronic inflammatory disease that is characterized by hyperplasia of the synovial fibroblasts, which is partly the result of decreased apoptosis. This study investigated the mechanisms through which curcumin, a polyphenolic compound from the rhizome of Curcuma longa, exerts its anti-proliferative action in the synovial fibroblasts obtained from patients with RA. Exposure of the synovial fibroblasts to curcumin resulted in growth inhibition and the induction of apoptosis, as measured by MTT assay, fluorescent microscopy and Annexin-V-based assay. RT-PCR and immunoblotting showed that treating the cells with curcumin resulted in the down-regulation of anti-apoptotic Bcl-2 and the X-linked inhibitor of the apoptosis protein as well as the up-regulation of pro-apoptotic Bax expression in a concentration-dependent manner. Curcumin-induced apoptosis was also associated with the proteolytic activation of caspase-3 and caspase-9, and the concomitant degradation of poly(ADP-ribose) polymerase protein. Furthermore, curcumin decreased the expression levels of the cyclooxygenase (COX)-2 mRNA and protein without causing significant changes in the COX-1 levels, which was correlated with the inhibition of prostaglandin E(2) synthesis. These results show that curcumin might help identify a new therapeutic pathway against hyperplasia of the synovial fibroblasts in RA.
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PMID:Curcumin induces apoptosis and inhibits prostaglandin E(2) production in synovial fibroblasts of patients with rheumatoid arthritis. 1767 42

Connections among specific proteins (Bax, Bcl-2, bFGF, COX-1, COX-2, E-cad, p15, p53, PCNA, TGFbeta3, TUNEL, vWF) in control of cell proliferation, apoptosis, cell adhesion, tumor vascularity and PGE2 content were evaluated in colon cancer as related to disease progression and survival. Tumor tissue and adjacent normal colon mucosa were obtained at curative resection in 22 patients. PGE2 concentrations were assessed in tumor tissue and tumor derived blood, splanchnic blood, peripheral venous blood and urine. Host inflammation was determined (CRP, ESR) in relationship to tumor differentiation and stage. Patients survived as expected according to Dukes A-D staging. Growth-related proteins correlated between tumor cells and stroma as well as between protein factors within tumor cells and tumor stroma. COX-2 predicted tumor tissue content of PGE2 (p<0.002), without reflection in tumor derived blood. Systemic inflammation was predicted by p15, TGFbeta3 and Bcl-2 in tumor tissue (p<0.001). p15 and vWF predicted reduced survival in ungrouped patients (p<0.02), while p15, PCNA, TGFbeta3 and vWF predicted reduced survival (p<0.0001) when patient grouping accounted for high tumor content of PGE2. Our results connect systemic inflammation and survival to COX-2 staining and increased PGE2 in colon cancer. Thus, it seems important to understand proximal signals behind upregulation of COX-2 and subsequent PGE2 production in certain tumor cells in colon cancer.
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PMID:Growth associated proteins in tumor cells and stroma related to disease progression of colon cancer accounting for tumor tissue PGE2 content. 1836 Jul 18

It is generally believed that the French paradox is related to the consumption of red wine and not other varieties of wine, including white wine or champagne. Some recent studies have indicated that white wine could also be as cardioprotective as red wine. The present investigation compares the cardioprotective abilities of red wine, white wine, and their principal cardioprotective constituents. Different groups of rats were gavaged with red wine, white wine, resveratrol, tyrosol, and hydroxytyrosol. Red wine and its constituent resveratrol and white wine and its constituents tyrosol and hydroxytyrosol all showed different degrees of cardioprotection as evidenced by their abilities to improve postischemic ventricular performance, reduce myocardial infarct size and cardiomyocyte apoptosis, and reduce peroxide formation. It was discovered in this study that although each of the wines and their components increased the enzymatic activities of the mitochondrial complex (I-IV) and citrate synthase, which play very important roles in oxidative phosphorylation and ATP synthesis, some of the groups were more complex-specific in inducing the activity compared to the other groups. Cardioprotective ability was further confirmed by increased expression of phospho-Akt, Bcl-2, eNOS, iNOS, COX-1, COX-2, Trx-1, Trx-2, and HO-1. The results of this study suggest that white wine can provide cardioprotection similar to red wine if it is rich in tyrosol and hydroxytyrosol.
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PMID:Does white wine qualify for French paradox? Comparison of the cardioprotective effects of red and white wines and their constituents: resveratrol, tyrosol, and hydroxytyrosol. 2241 30

Matrix metalloproteinase 9 (MMP-9) is a Zn(2+)-dependent endopeptidase that degrades some of the components of basement membranes and extracellular matrix and thus participates in leukocyte infiltration during inflammation. In a model of zymosan peritonitis, neutrophil infiltration in MMP-deficient (MMP-9(-/-)) mice was significantly weaker at the time of their maximal influx in wild-type mice (6h). However, during the late stages of peritonitis (24h) an extended accumulation of neutrophils was observed in MMP-9(-/-)versus the wild-type mice. Recently, we reported that the ratio of apoptosis of inflammatory leukocytes is impaired in MMP-9(-/-) mice during late peritonitis and the process depends on COX-1-driven PGE(2). Here we scrutinized the alterations in apoptotic mechanisms by comparisons between MMP-9(-/-) and the wild-type mice. Altered apoptosis occurred only during late (24h) peritonitis and concerned only neutrophils, and not macrophages, mast cells or lymphocytes. Furthermore, expression and activity of caspases was altered in MMP-9(-/-) animals, delayed for caspase-8 and -9, and decreased in the case of caspase-3. Also the expression of Bax/Bcl-2 proteins was changed in MMP-9(-/-) mice. These changes, and in particular the impaired neutrophil apoptosis and weaker caspase-3 activity, were restored by the selective COX-1 inhibition. We conclude that in mice lacking MMP-9 the enhanced COX-1-PGE(2) decreases caspase-3 expression and activity leading to impaired apoptosis of inflammatory neutrophils resulting in abnormal accumulation of the cells at the inflammatory focus. The data also reinforce the notion that MMP-9 is a key enzyme in neutrophil biology.
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PMID:Altered apoptosis of inflammatory neutrophils in MMP-9-deficient mice is due to lower expression and activity of caspase-3. 1968 97

Loading of the rat ulna is an ideal model to examine stress fracture healing. The aim of this study was to undertake a detailed examination of the histology, histomorphometry and gene expression of the healing and remodelling process initiated by fatigue loading of the rat ulna. Ulnae were harvested 1, 2, 4, 6, 8, and 10 weeks following creation of a stress fracture. Stress fracture healing involved direct remodelling that progressed along the fracture line as well as woven bone proliferation at the site of the fracture. Histomorphometry demonstrated rapid progression of basic multicellular units from 1 to 4 weeks with significant slowing down of healing by 10 weeks after loading. Quantitative PCR was performed at 4 hours, 24 hours, 4 days, 7 days, and 14 days after loading. Gene expression was compared to an unloaded control group. At 4 hours after fracture, there was a marked 220-fold increase (P<0.0001) in expression of IL-6. There were also prominent peak increases in mRNA expression for OPG, COX-2, and VEGF (all P<0.0001). At 24 hours, there was a peak increase in mRNA expression for IL-11 (73-fold increase, P<0.0001). At 4 days, there was a significant increase in mRNA expression for Bcl-2, COX-1, IGF-1, OPN, and SDF-1. At 7 days, there was significantly increased mRNA expression of RANKL and OPN. Prominent, upregulation of COX-2, VEGF, OPG, SDF-1, BMP-2, and SOST prior to peak expression of RANKL indicates the importance of these factors in mediating directed remodelling of the fracture line. Dramatic, early upregulation of IL-6 and IL-11 demonstrate their central role in initiating signalling events for remodelling and stress fracture healing.
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PMID:Temporal pattern of gene expression and histology of stress fracture healing. 1983 76


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