Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that the introduction of human recombinant wild-type p53 mediated by an adenoviral vector (Ad5CMV-p53), either alone or delivered in combination with ionizing radiation, was cytotoxic to two nasopharyngeal carcinoma (NPC) cell lines. To further explore the potential therapeutic role for gene therapy, the combination of Ad5CMV-p53 and cisplatin was examined in two NPC cell lines, CNE-1 and C666-1. The C666-1 cells are particularly relevant because they express Epstein-Barr virus latent gene products analogous to human NPC in situ. Cells were infected with 5 pfu/cell of Ad5CMV-p53 or Ad5CMV-beta-gal, followed by exposure to increasing doses of cisplatin. Clonogenic and MTT assays were used to assess the sensitivity of cells to these treatments, and apoptosis was also quantified. The combination of Ad5CMV-p53 and cisplatin resulted in approximately 25% greater cytotoxicity compared to that observed with cisplatin alone in either cell line. Apoptosis was induced in approximately 50% of cells following administration of both Ad5CMV-p53 and cisplatin, but was induced in considerably fewer cells following either treatment alone. The two modalities appeared to interact in an additive manner. Ad5CMV-p53 gene therapy resulted in the expression of biologically active p53 protein, shown by induction of p21(WAF1/CIP1). Cisplatin treatment showed little effect on either p53 or p21(WAF1/CIP1) expression. Therefore, both p53 gene therapy and cisplatin chemotherapy demonstrated cytotoxicity mediated by apoptosis despite the presence of EBV gene products in the C666-1 cells, but it appears that the two modalities induce cytotoxicity by independent pathways.
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PMID:Cisplatin chemotherapy plus adenoviral p53 gene therapy in EBV-positive and -negative nasopharyngeal carcinoma. 1147 55

We obtained a pulmonary alveolar type II epithelial cell line, MAC7, derived from the lung of p53-deficient mice (p53 -/-). When this cell line was passaged for long periods of time, the epithelial cells grew at a high rate for over 50th passage and never entered the non-growing senescent phase characteristic of the normal cells (p53 +/+). Each pulmonary epithelial outgrowth was characterized morphologically and immunocytochemically, and the growth and viability of the outgrowths were examined by MTT assay. Expression of surfactant-associated protein, SP-B, was detected, and transmission electron microscopy demonstrated a type II phenotype containing lamellar bodies and phospholipids. These findings indicate that MAC7 cells retain the morphological and physiological properties of alveolar type II epithelial cells. This cell line should be useful in experimental systems for studying lung pathology.
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PMID:Establishment of pulmonary alveolar type II cell line from p53-deficient mice. 1147 91

We evaluated the potential activity of novel N-1-sulfonyl derivatives of pyrimidine bases uracil and cytosine on pancreatic carcinoma cells (MIAPaCa2), colon carcinomas cells (HT-29, CaCo2), cervical carcinoma cells (HeLa) and poorly-differentiated cells from lymph node metastasis of colon carcinoma (SW-620). The cytotoxicity of N-1-sulfonylpyrimidine derivatives was analyzed with the MTT cell survival assay and their antiproliferative activity was measured via radioactive precursors incorporation assay. The N-1-sulfonylpyrimidine derivatives affected the growth of all examined cell lines at concentrations of 10(-8)-10(-5) M, by 25-70%. Growth inhibition depended on the tumor cell line type and the concentration of investigated compounds. The compounds 2, 4, 7, 8 and 9 inhibited DNA, RNA and protein synthesis in CaCo2, MIAPaCa2 and HeLa cells. The exposure of tumor cells in vitro to compounds 2, 4, 7, 8, 9, 10 and 11, at the 10(-6) M concentration, caused both morphological (condensation of chromatin, cell shrinkage), as well as biochemical changes (ladder pattern of DNA fragmentation and exposure of phosphatidylserine on outer lipid bilayer plasma membrane) characteristic of apoptosis. After 24 hours of the N-1-sulfonylpyrimidine derivative application, the p53 oncoprotein expression could not be detected by immunocytochemical analysis. On the basis of present results it can be concluded that novel N-1-sulfonylpyrimidine derivatives are promising antitumor agents with a strong antiproliferative activity and an ability to induce apoptosis in treated tumor cells.
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PMID:Antineoplastic activity of novel N-1-sulfonypyrimidine derivatives. 1149 87

Progesterone has been used as an ingredient of anticancer drug for patients with ovarian carcinoma. However, the mechanism of anticancer effects by progesterone has not been understood. In this study, the effects of progesterone on ovarian cancer cells, SNU-840, were investigated. After the incubation with progesterone, the viability of the cells was evaluated by MTT assay. As a result, 45% of the cells were viable after 48 h of incubation with 100 microM progesterone. In addition, [(3)H]thymidine incorporation assay showed that the proliferation of the cells was completely inhibited by progesterone after 48 h of incubation at 100 microM concentration. Colorimetric TUNEL assay revealed the fragmentation of the chromosomal DNA, suggesting that the process of the cell death was apoptosis. The level of the p53 mRNA was determined by northern blotting assay, since many apoptosis processes are mediated by up-regulation of the p53 expression. The level of the p53 mRNA reached its maximum at 12 h and decreased after 24 h of incubation with progesterone. In conclusion, progesterone inhibits the proliferation and elicits apoptosis of SNU-840 cells. Also, it up-regulates the p53 mRNA transiently.
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PMID:Apoptosis induced by progesterone in human ovarian cancer cell line SNU-840. 1150 Sep 21

Aspirin- and non-steroidal anti-inflammatory drug (NSAID)-induced apoptosis is one of the important mechanisms for their anti-tumour effect in gastric cancer. We aimed at determining the role of bcl-2 family proteins and caspases in the apoptotic process. Gastric cancer cell lines AGS (wild-type p53) and MKN-28 (mutant p53) were used. Cell proliferation was measured by MTT assay. Apoptosis was determined by acridine orange staining. Protein expressions were determined by western blotting. Aspirin and indomethacin inhibited cell proliferation and induced apoptosis in both cells. AGS cells were more sensitive compared with MKN-28 cells. The pro-apoptotic proteins bax and bak were overexpressed after treatment, while the protein level of bcl-2 remained unchanged. Apoptosis was accompanied by an increase in caspase-3 activity and cleavage of caspase-3 and poly(ADP-ribose) polymerase. Inhibition of caspase-3 rescued aspirin-induced apoptosis. Our results suggest that one of the major pathways which mediates the anti-tumour response of aspirin and indomethacin in gastric cancer cells is through up-regulation of bax and bak and activation of caspase-3. Bax and bak are important in the chemoprevention of gastric cancer.
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PMID:Non-steroidal anti-inflammatory drugs induce apoptosis in gastric cancer cells through up-regulation of bax and bak. 1153 60

After exposure of H460 cells to an increasing concentrations of cis-diammine-dichloroplatinum(II) (cisplatin, CDDP) for 6 months, cisplatin resistant cells were isolated (H460/CIS). The biologic behaviors of H460 and H460/CIS cells were tested using animal experiments. Only the resistant cells developed lung metastases despite cisplatin treatment. The characteristics of H460/CIS cells are as follows, MTT analyses revealed that H460/CIS cells were markedly resistant to cisplatin compared with their parental cells. Also, H460/CIS cells exhibited cross-resistance to DNA damaging agents such as doxorubicin (DXR) and etoposide. Cisplatin treatment dramatically increased p53 expression in parental cells but not in H460/CIS cells which expressed basal levels of p53. Without cisplatin treatment, Bcl-2 and Bax were expressed in H460/CIS cells, but not in parental cell. Our data suggested that p53, Bax and Bcl-2 were up-regulated in H460/CIS cells. These changes could explain some of the mechanisms of cisplatin resistance. Thus, H460/CIS could be useful to investigate the mechanisms of drug resistance to cisplatin including apoptotic gene expressions conferring drug resistance, thereby making progress in the treatment of cisplatin-resistant tumor cells.
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PMID:In vitro establishment of cis-diammine-dichloroplatinum(II) resistant lung cancer cell line and modulation of apoptotic gene expression as a mechanism of resistant phenotype. 1155 17

This study was made to investigate whether Chiropsalmus Quadrigatus toxins (CqTX), which isolated from box jellyfish C. Quadrigatus venom, could induce apoptosis in human U251 and rat C6 malignant glioma cells and transformed vascular endothelial ECV 304 cell lines. Cell viability was estimated by MTT assay. Apoptosis was evaluated using TdT (terminal deoxynucleotidyl transferase)-mediated dUTP nick-end labeling (TUNEL) method and DNA gel electrophoresis. Furthermore, the expression of p53 protein was examined immunohistochemically in the U251 cells. After the CqTX treatment, the growth of all cell lines was inhibited, the fragmented DNA was observed and some cells became TUNEL positive. The expression of p53 protein was increased in the tested U251 cells. The results suggested that CqTX induced apoptosis in these cell lines. The promotion of the p53 expression might be one mechanism of apoptosis induced by CqTX in the glioma cells.
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PMID:Apoptosis induced by box jellyfish (Chiropsalmus quadrigatus) toxin in glioma and vascular endothelial cell lines. 1173 37

Ethanol impairs insulin-stimulated survival and mitochondrial function in immature proliferating neuronal cells due to marked inhibition of downstream signaling through P13 kinase. The present study demonstrates that, in contrast to immature neuronal cells, the major adverse effect of chronic ethanol exposure (50 mM) in post-mitotic rat cerebellar granule neurons is to inhibit insulin-stimulated mitochondrial function (MTT activity, MitoTracker Red fluorescence, and cytochrome oxidase immunoreactivity). Ethanol-impaired mitochondrial function was associated with increased expression of the p53 and CD95 pro-apoptosis genes, reduced Calcein AM retention (a measure of membrane integrity), increased SYTOX Green and propidium iodide uptake (indices of membrane permeability), and increased oxidant production (dihydrorosamine fluorescence and H2O2 generation). The findings of reduced membrane integrity and mitochondrial function in short-term (24 h) ethanol-exposed neurons indicate that these adverse effects of ethanol can develop rapidly and do not require chronic neurotoxic injury. A role for caspase activation as a mediator of impaired mitochondrial function was demonstrated by the partial rescue observed in cells that were pre-treated with broad-spectrum caspase inhibitors. Finally, we obtained evidence that the inhibitory effects of ethanol on mitochondrial function and membrane integrity were greater in insulin-stimulated compared with nerve growth factor-stimulated cultures. These observations suggest that activation of insulin-independent signaling pathways, or the use of insulin sensitizer agents that enhance insulin signaling may help preserve viability and function in neurons injured by gestational exposure to ethanol.
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PMID:Ethanol impairs insulin-stimulated mitochondrial function in cerebellar granule neurons. 1176 90

Elevated levels of epidermal growth factor receptor in head and neck cancer have been extensively reported, and are correlated with poor prognosis. The combination of cisplatin and 5-fluorouracil is a standard treatment regimen for head and neck cancer, with radiation representing another therapeutic option. Six head and neck cancer cell lines were used to study the cytotoxic effects of combining ZD1839 ('Iressa'), a new selective epidermal growth factor receptor tyrosine kinase inhibitor, and radiation. Two of the cell lines were also used to study the combination of ZD1839 and cisplatin/5-fluorouracil. Cytotoxic effects were assessed by the MTT test. The results indicated that ZD1839 applied before radiation gave the best effects (P=0.002); an effect that was strongest in those p53-mutated cell lines that express the highest epidermal growth factor receptor levels. The effects of ZD1839 with cisplatin and/or 5-fluorouracil were sequence dependent (P<0.003), with the best results achieved when ZD1839 was applied first. For the triple combinations, ZD1839 applied before cisplatin and 5-fluorouracil resulted in a slight synergistic effect (P=0.03), although the effect was greater when ZD1839 was applied both before and during cytotoxic drug exposure. In conclusion, ZD1839 applied before radiation and before and/or during cisplatin/5-fluorouracil may improve the efficacy of treatment for head and neck cancer.
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PMID:Sequence-dependent effects of ZD1839 ('Iressa') in combination with cytotoxic treatment in human head and neck cancer. 1187 48

The effects of nitric oxide (NO) donor sodium nitroprusside (SNP) on the proliferation and apoptosis and on Bcl-2, Bax and p53 proteins of pulmonary fibroblasts were investigated by using MTT cleavage assay, agarose gel electrophoresis and flow cytometric analysis. The results showed increases in the optical density (550 nm) of MTT cleavage assay, the number of cells and the proliferation index (PI), in comparison with the control. The number of apoptotic cells was also increased, though the percentage of apoptotic cells was too low to reveal oligonucleosomal fragmentation of characteristic ladder pattern, which is associated with apoptosis. In the meantime, the level of Bcl-2 decreased and that of Bax increased, while the p53 remained unchanged. These results suggest that exogenous NO has a dual effect on proliferation and apoptosis; and the action of NO on pulmonary fibroblasts is mainly proliferative. Down regulation of Bcl-2 and up regulation of Bax are implicated in the molecular mechanisms of this action.
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PMID:Promotion of pulmonary fibroblast proliferation and apoptosis by sodium nitroprusside. 1193 Feb 31


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