Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P04637 (p53)
77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fruiting body of Antrodia camphorata is well known in Taiwan as a traditional medicine for treating cancer and inflammation. The purpose of this study was to evaluate the apoptotic effects of ethylacetate extract from A. camphorata (EAC) fruiting bodies in two human liver cancer cell lines, Hep G2 and PLC/PRF/5. Treatment with EAC decreased the cell growth of Hep G2 and PLC/PRF/5 cells in a dose dependent manner. In Fas/APO-1 positive-Hep G2 cells, EAC increased the expression level of Fas/APO-1 and its two forms of ligands, membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), in a p53-indenpendent manner. In addition, EAC also initiated mitochondrial apoptotic pathway through regulation of Bcl-2 family proteins expression, release of cytochrome c, and activation of caspase-9 both in Hep G2 and PLC/PRF/5 cells. Furthermore, EAC also inhibited the cell survival signaling by enhancing the amount of IkappaBalpha in cytoplasm and reducing the level and activity of NF-kappaB in the nucleus, and subsequently attenuated the expression of Bcl-X(L) in Hep G2 and PLC/PRF/5 cells. EAC therefore decreased the cell growth and induced apoptosis both in Hep G2 and PLC/PRF/5 cells.
...
PMID:Apoptotic effects of extract from Antrodia camphorata fruiting bodies in human hepatocellular carcinoma cell lines. 1579 30

Chalcones are discussed to represent cancer preventive food components in a human diet that is rich in fruits and vegetables. In this study, we examined chalcone (1,3-diphenyl-2-propenone) for its effect on proliferation in human breast cancer cell lines, MCF-7 and MDA-MB-231. The results showed that chalcone inhibited the proliferation of MCF-7 and MDA-MB-231 by inducing apoptosis and blocking cell cycle progression in the G2/M phase. Immunoblot assay showed that chalcone significantly decreased the expression of cyclin B1, cyclin A and Cdc2 protein, as well as increased the expression of p21 and p27 in a p53-independent manner, contributing to cell cycle arrest. An enhancement in Fas/APO-1 and its two form ligands, membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), was responsible for the apoptotic effect induced by chalcone. In addition, chalcone also triggered the mitochondrial apoptotic signaling by increasing the amount of Bax and Bak and reducing the level of Bcl-2 and Bcl-X(L), and subsequently activated caspase-9 in MCF-7 and MDA-MB-231 cells. Taken together, our study suggests that the blockade of cell cycle progression and initiation of cell apoptotic system may participate in the antiproliferative activity of chalcone in human breast cancer cells.
...
PMID:Chalcone inhibits the proliferation of human breast cancer cell by blocking cell cycle progression and inducing apoptosis. 1630 39

Stannin (Snn) was discovered using subtractive hybridization methodology designed to find gene products related to selective organotin toxicity and apoptosis. The cDNAs for Snn were first isolated from brain tissues sensitive to trimethyltin, and were subsequently used to localize, characterize, and identify genomic DNA, and other gene products of Snn. Snn is a highly conserved, 88 amino acid protein found primarily in vertebrates. There is a minor divergence in the C-terminal sequence between amphibians and primates, but a nearly complete conservation of the first 60 residues in all vertebrates sequenced to date. Snn is a membrane-bound protein and is localized, in part, to the mitochondria and other vesicular organelles, suggesting that both localization and conservation are significant for the overall function of the protein. The structure of Snn in a micellar environment and its architecture in lipid bilayers have been determined using a combination of solution and solid-state NMR, respectively. Snn structure comprised a single transmembrane domain (residues 10-33), a 28-residue linker region from residues 34-60 that contains a conserved CXC metal binding motif and a putative 14-3-3xi binding region, and a cytoplasmic helix (residues 61-79), which is partially embedded into the membrane. Of primary interest is understanding how this highly-conserved peptide with an interesting structure and cellular localization transmits both normal and potentially toxic signals within the cell. Evidence to date suggests that organotins such as trimethyltin interact with the CXC region of Snn, which is vicinal to the putative 14-3-3 binding site. In vitro transfection analyses and microarray experiments have inferred a possible role of Snn in several key signaling systems, including activation of the p38-ERK cascade, p53-dependent pathways, and 14-3-3xi protein-mediated processes. TNFalpha can induce Snn mRNA expression in endothelial cells in a PKC-epsilon dependent manner. Studies with Snn siRNA suggest that this protein may be involved in growth regulation, since inhibition of Snn expression alone leads to reduced endothelial cells growth and induction of COP-1, a negative regulator of p53 function. A key piece of the puzzle, however, is how and why such a highly-conserved protein, localized to mitochondria, interacts with other regulatory proteins to alter growth and apoptosis. By knowing the structure, location, and possible signaling pathways involved, we propose that Snn constitutes an important sensor of mitochondrial damage, and plays a key role in the mediation of cross-talk between mitochondrial and nuclear compartments in specific cell types.
...
PMID:Functional and structural properties of stannin: roles in cellular growth, selective toxicity, and mitochondrial responses to injury. 1645 79

The insulin-like growth factor (IGF) system plays an important role in the biology of breast cancer. Most of the biological actions of IGF-I and IGF-II are mediated by the IGF-I receptor (IGF-IR), a membrane-bound heterotetramer with potent antiapoptotic and cell survival activities. Caveolin-1 (Cav-1) is one of the main components of caveolae, and it has been shown to interact with multiple signaling molecules. In view of the important roles of IGF-IR and Cav-1 in oncogenically transformed mammary gland cells, in the present study we addressed the potential regulation of IGF-IR gene expression by Cav-1. The results obtained showed that MCF7/Cav-1 cells, expressing the Cav-1 gene in a stable manner, contain significantly higher levels of IGF-IR protein and mRNA than native MCF7 cells. These elevated levels of expression are mediated at the level of transcription, as shown by the results of experiments showing that the activity of the proximal IGF-IR promoter was higher in Cav-1-expressing MCF7 cells than in untransfected MCF7 cells. Furthermore, in subcellular localization studies, intensive IGF-IR staining in membrane ruffles and projections in MCF7/Cav-1 cells were noted, in contrast to typical membrane staining in MCF7 cells. In addition, we demonstrated that transcriptional activation of the IGF-IR gene by Cav-1 requires an intact p53 signaling pathway, since Cav-1 was unable to elevate IGF-IR levels in p53-null cells. Finally, the effect of Cav-1 was associated with an elevation in the levels of Sp1, a zinc-finger protein with important roles in IGF-IR gene transactivation. In summary, we identified the IGF-IR gene as a downstream target for Cav-1 action in breast cancer cells.
...
PMID:Caveolin-1 up-regulates IGF-I receptor gene transcription in breast cancer cells via Sp1- and p53-dependent pathways. 1701 45

Apoptosis of vascular smooth muscle cells (VSMC) plays an important role in remodeling the vessel walls, one of the major determinants of long-term blood pressure elevation and an independent risk factor for cardiovascular morbidity and mortality. Apoptosis in VSMC can be inhibited by inversion of the intracellular [Na+]/[K+] ratio after the sustained blockage of the Na+,K+-ATPase by ouabain. Using two-dimensional gel electrophoresis followed by tandem mass spectroscopy, we compared proteomes of control VSMC and of those with ouabain-inhibited Na+,K+-ATPase and found that ouabain treatment led to overexpression of numerous soluble and membrane-bound proteins. Among proteins, which showed the highest level of ouabain-induced expression, we identified mortalin (also known as GRP75 or PBP-74), a member of the heat shock protein 70 superfamily and a marker for cellular mortal and immortal phenotypes. Further experiments showed that mortalin RNA and protein levels are induced in ouabain-treated VSMC, and that transient transfection of cells with mortalin cDNA inhibited serum deprivation-induced apoptosis via inactivation of the tumor suppressor gene, p53.
...
PMID:Proteomic analysis of vascular smooth muscle cells treated with ouabain. 1717 93

1. Paeoniflorin (PF), isolated from the paeony root, is reported to have immunoregulatory, neuromuscular blocking, anticonvulsant, antihyperglycaemic and antihypotensive effects. 2. The present study investigated the antiproliferative activity of PF. The results showed that PF inhibited the proliferation of A549 by blocking cell cycle progression in the G(0)/G(1) phase and inducing apoptosis. 3. An ELISA showed that G(0)/G(1) phase arrest may be due to p53-independent induction of p21/wild-type p53-activated fragment 1 (WAF1). Increased protein expression of Fas/apoptosis-1 (APO-1) and its two ligands, membrane-bound Fas ligand and soluble Fas ligand, may be responsible for the PF-induced apoptosis. 4. This is the first study to show that the induction of p21/WAF1 and the activity of the Fas/Fas ligand apoptotic system may participate in the antiproliferative activity of PF in A549 cells.
...
PMID:Antiproliferative activity of paeoniflorin is through cell cycle arrest and the Fas/Fas ligand-mediated apoptotic pathway in human non-small cell lung cancer A549 cells. 1794 99

Semicarbazide sensitive amine oxidase (SSAO) is a multifunctional enzyme present mainly in adipocytes, endothelial and smooth muscle cells. It metabolizes primary aliphatic and aromatic amines generating products able to contribute to cellular oxidative stress. SSAO is expressed in a membrane-bound form and is also present as a soluble enzyme in plasma. Both isoforms are increased in several pathologies, and the catalytic products generated by the soluble enzymatic activity can induce cytotoxicity of vascular cells in culture. We have analyzed whether the transmembrane form of the enzyme is able to produce a cytotoxic effect through methylamine oxidation. Since cells in culture lose the expression of this enzyme, we used an SSAO stably transfected smooth muscle cell line. Herein we report that cell treatment with the substrate methylamine induced a dose and time dependent cytotoxic effect. The tumor suppressor protein p53 played an important role in the molecular pathway involved in this cell death. Moreover, we also observed the induction of PUMA-alpha expression with mitochondrial Bcl-2 family proteins being affected, and final effector caspases being activated.
...
PMID:p53 phosphorylation is involved in vascular cell death induced by the catalytic activity of membrane-bound SSAO/VAP-1. 1834 72

Aucubin, an iridoid glycoside isolated from the leaves of Aucuba japonica, inhibits human non-small cell lung cancer A549 cells by blocking cell cycle progression in the G(0)/G(1) phase and inducing apoptosis. An ELISA showed that the G(0)/G(1) phase arrest is due to p53-mediated induction of p21. Enhancement of Fas and its two ligands, membrane-bound and soluble Fas ligand, may be responsible for the apoptotic effect induced by aucubin. The present study shows, for the first time, that the induction of p53 and activity of the Fas/Fas ligand apoptotic system may participate in the antiproliferative activity of aucubin in A549 cells.
...
PMID:Antiproliferative activity of aucubin is through cell cycle arrest and apoptosis in human non-small cell lung cancer A549 cells. 1878 1

Tetrazolium violet (TV), a tetrazolium salt, has been applied in several fields, including estimating respiration rate, as a redox indicator of microbial growth, and for estimating the number of viable animal cells. It has recently been found that TV is capable of inducing apoptosis in rat glioblastoma cells by way of an elusive mechanism. In this study, we demonstrated that TV also induced apoptosis in mouse breast tumor C127 cells as evidenced by nucleus condensation and nucleus fragmentation. Our data showed that TV caused activation of caspase-3 and caspase-8, but not caspase-9. An enhancement in Fas and its two ligands, membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), might be responsible for the apoptotic effect induced by TV. Also, the results first reported that TV not only inhibited C127 cells proliferation but also blocked cell cycle progression in the G1 and G2 phase, determined by MTT assay and flow cytometry analysis. Immunofluorescence assay demonstrated that TV significantly increased the expression of p53 protein, which caused cell cycle arrest. Taken together, p53, Fas/FasL, and the caspase apoptotic system may participate in the antiproliferative activity of TV in C127 cells.
...
PMID:Tetrazolium violet inhibits cell growth and induces cell death in C127 mouse breast tumor cells. 1854 55

DNA damage induced apoptosis, along with precise DNA damage repair, is a critical cellular function, and both of these functions are necessary for cancer prevention. The NBS1 protein is known to be a key regulator of DNA damage repair. It acts by forming a complex with Rad50/Mre11 and by activating ATM. We show here that NBS1 regulates a novel p53 independent apoptotic pathway in response to DNA damage. DNA damage induced apoptosis was significantly reduced in NBS1 deficient cells regardless of their p53 status. Experiments using a series of cell lines expressing mutant NBS1 proteins revealed that NBS1 is able to regulate the activation of Bax and Caspase-3 without the FHA, Mre11-binding, or the ATM-interacting domains, whereas the phosphorylation sites of NBS1 were essential for Bax activation. Expression of apoptosis-related transcription factors such as E2F1 and their downstream pro-apoptotic factors were not related to this apoptosis induction. Interestingly, NBS1 regulates a novel Bax activation pathway by disrupting the Ku70-Bax complex which is required for activation of the mitochondrial apoptotic pathway. This dissociation of the Ku70-Bax complex can be mediated by acetylation of Ku70, and NBS1 can function in this process through a protein-protein interaction with Ku70. Thus, NBS1 is a key protein involved in the prevention of carcinogenesis, not only through the precise repair of damaged DNA by homologous recombination (HR) but also by its role in the elimination of inappropriately repaired cells.
...
PMID:NBS1 regulates a novel apoptotic pathway through Bax activation. 1864 72


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---