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)

N-(4-hydroxyphenyl)-retinamide (fenretinide) is a synthetic derivative of all-trans-retinoic acid and induces apoptosis in several cancer cell lines. We determined the anti-cancer activity of fenretinide using human hepatoma cell lines, Bel-7402, HepG2 and Smmc-7721. An in-vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that fenretinide exhibited growth inhibition in these cell lines, with IC50 values ranging from 13.1 to 15.5 micromol/l. In Bel-7402 cells, apoptosis with 15 micromol/l fenretinide for 0 and 48 h was 3 and 48%, respectively. In-vivo studies using the Bel-7402 xenografted athymic mouse model showed tumor inhibition rates ranging from 37.2 to 57.2%, with fenretinide administration once per 3 days at the rate of 25-100 mg/kg. Western blot analysis further showed down-regulation of procaspase-3, X-linked inhibitor of apoptosis protein and poly(ADP-ribose) polymerase cleavage in Bel-7402 cells treated with 15 mumol/l fenretinide for 48 h. Overexpression of p53 was observed in a time-dependent manner, along with a decrease in the Bcl-2/Bax ratio. Depolarized mitochondrial membranes were found in fenretinide-induced apoptotic cells, in a time-dependent manner. We conclude that fenretinide effectively inhibits the proliferation of Bel-7402, both in vitro and in vivo. Both procaspase-3 and p53-mediated apoptotic pathways are involved in its potent anti-cancer activity.
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PMID:Anti-proliferative activity of fenretinide in human hepatoma cells in vitro and in vivo. 1715 2

Experiments were performed in C57BL/6J male mice to determine the effects of acetylcholinesterase (AChE) inhibitor pyridostigmine bromide (PB) and stress on cardiovascular function, structure, and apoptosis. Mice were studied for seven days under the following conditions: Controls (osmotic minipump with saline), PB (10 mg/kg/day, minipumps), shaker stress (45 stressors/day, minipump with saline) and PB+Stress combination. AChE activity was significantly reduced in all PB-treated mice. PB caused no changes in 24-h mean arterial pressure (MAP) or heart rate (HR). Stress increased 24-h MAP on day 1 and 24-h HR on day 7 in both Stress and PB+Stress groups. A significant reduction in the aortic wall thickness/diameter ratio (P <0.05 vs. control) and slightly reduced relative heart weight were observed in the PB group. These effects were blunted by simultaneous stress exposure. Immunochemistry was used to stain for Bax and Bcl-2 (apoptosis markers). There was a four-fold increase in Bax/Bcl-2 ratio in the heart of PB and PB+Stress treated mice while an attenuation was observed in aortic endothelium. Results suggest that a relatively short-term continuous PB exposure may have adverse effects on the heart and blood vessels, independently of changes in MAP and HR.
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PMID:Acetylcholinesterase inhibition affects cardiovascular structure in mice. 1717 30

Earlier studies showed that melatonin reduced the growth of 17-beta-estradiol (E(2))-induced rat pituitary prolactin-secreting tumor (prolactinoma) in vivo. The mechanisms of melatonin's inhibitory action on the prolactin-secreting tumor were further explored by investigating the in vitro effects of melatonin on the growth of pituitary prolactin-secreting tumor cells. Primary cultured prolactinoma cells from E(2)-induced rat pituitary prolactin-secreting tumor were treated with 10(-5), 10(-4) or 10(-3) m melatonin for 5 days. Apoptosis was evaluated using flow cytometry and the TdT-mediated dUTP nick-end labeling (TUNEL) method. In addition, cell viability was analyzed by (3,4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It was found that incubation of prolactinoma cells with 10(-5), 10(-4) or 10(-3) m melatonin for 5 days inhibited cell growth and increased cell apoptosis. Furthermore, melatonin increased caspase-3 activity, Bax mRNA expression, and cytochrome c protein expression. Conversely, Bcl-2 mRNA expression and mitochondrial membrane potential were inhibited by melatonin treatment. Our results further suggest that melatonin inhibits tumor growth by inducing apoptosis of rat pituitary prolactin-secreting tumor directly via the damage of mitochondria.
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PMID:Antiproliferative effects of melatonin on the growth of rat pituitary prolactin-secreting tumor cells in vitro. 1728 50

Cyclooxygenase-2 (COX-2) inhibitors have been shown to exert inhibitory effects on many types of malignant tumors and several groups have suggested that COX-2 inhibitors enhance the cytotoxic effects of other anti-cancer agents. We previously reported that meloxicam has an anti-tumorigenic effect on COX-2-expressing osteosarcoma cells. In the current study, we evaluated the synergy between meloxicam and cisplatin (CDDP), doxorubicin (DXR) and 4-hydroperoxy ifosfamide (4OOH-IFM), using the human osteosarcoma cell line, MG-63. Cytotoxicity was determined using 3-(4,5'-dimethylthiazol-2-yl)-2,5'-diphenyltetrazolium bromide (MTT) assays, and isobolographic analysis was used to evaluate any synergy. Apoptotic activity was determined by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL), and by evaluating Bax and Bcl-2 expression levels using real-time RT-PCR and western blotting analysis. Cell cycling was evaluated by flow cytometry. The cytotoxic effects of CDDP and DXR were enhanced synergistically in the presence of meloxicam and were partially due to an increase in apoptosis. By contrast, meloxicam enhanced neither the cytotoxic nor the apoptotic activity of 4OOH-IFM. Combining meloxicam with DXR significantly up-regulated Bax expression, whereas it down-regulated Bcl-2 expression in combination with CDDP. Furthermore, the number of cells in the G2/M phase was significantly increased in DXR-treated samples by the addition of meloxicam, but not in CDDP-treated or 4OOH-IFM-treated samples. These results suggest a potential clinical application of meloxicam in combination with cytotoxic drugs in patients with COX-2-positive osteosarcoma.
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PMID:Synergistic effects of meloxicam and conventional cytotoxic drugs in human MG-63 osteosarcoma cells. 1739 21

In the case of left ventricle remodeling after myocardial infarction, cardiomyocyte apoptosis is attributed to increased cardiac workload by the stimulus such as chronic hypoxia. B-Type natriuretic peptide, being known as a reliable prognostic of cardiovascular pathology, plays an important role in the myocardial infarction. However, the action of B-type natriuretic peptide on cardiomyocytes undergoing apoptosis is unclear. In the present study, B-type natriuretic peptide have exhibited the enhancive effects on the mild hypoxia-induced cardiomyocyte apoptosis with the manifestation of facilitating phosphatidylserine evagination and increasing typical fragmented nuclei. In addition, B-type natriuretic peptide aggravated the dissipation of delta psi(m), the depletion of intracellular ATP and the increase of caspase-3 activity. 8-Bromo-cGMP, which increased cGMP independent of B-type natriuretic peptide, could mimic B-type natriuretic peptide's effects; whereas cGMP-dependent protein kinase inhibitor, Rp-8-br-cGMP inhibited that. Further study revealed the enhancive effect of BNP on down-regulation of Bcl-2 mRNA expression in the presence of mild hypoxia. In conclusion, the present study demonstrated that B-type natriuretic peptide aggravated the cardiomyocyte apoptosis by influencing hypoxia-induced mitochondrial death pathway, which is true at least in this oxygen deprivation model; and this effect was partially realized through intracellular cGMP.
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PMID:B-type natriuretic peptide enhances mild hypoxia-induced apoptotic cell death in cardiomyocytes. 1754 Nov 58

Objective To investigate the effects of 14-3-3 protein overexpression on the 1-methyl-4-phenylpyridinium (MPP(+)) induced pheochromocytoma (PC12) cell death and the potential mechanisms. Methods pcDNA3.1(+)-14-3-3 plasmids, which could be expressed in mammalian cell, were constructed and transfected into PC12 cells with Lipofectamine 2000. The expression of 14-3-3 protein, Bcl-2 protein, and BAD protein were determined by western blot. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, microplate reader, and flow cytometric analysis were used to measure cell viability, the caspase activity, and apoptotic ratio respectively. Results (1) The expression of 14-3-3 protein increased significantly three weeks after pcDNA3.1 (+)-14-3-3 plasmids transfected into PC12 cells. (2) MPP(+) caused a decrease of cell viability in a dose-dependent manner. At 100 mu mol/L MPP(+), cell viability reduced approximately 50%. (3) The caspase activity increased along with the MPP(+) concentrations rising and reached its maximum value (0.34 mu mol/mg protein) at 100 mu mol/L MPP(+). However caspase activity decreased significantly when the MPP(+) concentration exceeded 100 mu mol/L. (4) Overexpression of 14-3-3 protein decreased the apoptosis ratio of PC12 cells treated with 100 mu mol/L MPP(+) from 26.5% to 8.6%. (5) Bcl-2 protein tended to decrease but BAD protein tended to increase after treatment of PC12 cells with 100 mu mol/L MPP(+). Overexpression of 14-3-3 protein significantly increased the cellular level of Bcl-2 protein and decreased that of BAD protein. Conclusion Overexpression of 14-3-3 protein may reduce MPP(+)-induced apoptotic cell death in PC12 cells by up-regulating the Bcl-2 expression and down-regulating the BAD expression. These results may provide a promising target for treatment of Parkinson' s disease.
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PMID:Overexpression of 14-3-3 protein protects pheochromocytoma cells against 1-methyl-4-phenylpyridinium toxicity. 1769 Jul 28

Triptolide, derived from the traditional Chinese herb, Tripterygium wilfordii, sensitizes cancer cells to apoptosis. Glioblastoma multiforme (GBM), which accounts for most cases of central nervous malignancy, has a very poor prognosis and lacks effective therapeutic inventions. We, therefore, investigated the effects of different concentrations of, and different periods of exposure to, triptolide on cell proliferation and apoptosis in the glioma cell lines, U251MG and U87MG, and in normal human fetal astrocytes. Cell proliferation was investigated by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay and growth curve analysis, and apoptosis was assessed from genomic DNA fragmentation. Triptolide showed dose-dependent inhibition of cell proliferation and induction of apoptosis in glioma cells. It also increased the ratio of the pro-apoptotic protein, Bax, to the anti-apoptotic protein, Bcl-2. Since U87MG has the wild-type p53 gene whereas U251MG harbours a mutated p53 gene, our results indicate that triptolide induces apoptosis in GBM cells via a p53-independent pathway. The dose-dependent inhibition of cell proliferation and induction of apoptosis by triptolide may involve upregulation of Bax and downregulation of Bcl-2.
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PMID:The effect of triptolide on apoptosis of glioblastoma multiforme (GBM) cells. 1790 Apr 3

Sulfur is commonly used in Asia as an herbal medicine to treat inflammation and cancer, and potent chemopreventive effects have been demonstrated in various in vivo and in vitro models for sulfur-containing compounds found in naturally occurring products. Here, we report the growth inhibitory and apoptosis-related effects of a newly developed highly purified sulfur (HPS) on immortalized human oral keratinocytes (IHOKs) and on oral cancer cells representing two stages of oral cancer (HN4, HN12) based on a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Western blotting, cell cycle analysis, and nuclear staining. The purity of the sulfur preparation was verified by high-performance liquid chromatography. HPS inhibited the proliferation of immortalized and malignant oral keratinocytes in a dose- and time-dependent manner. FITC-annexin V staining, DNA fragmentation testing, and Hoechst 33258 staining revealed that HPS inhibited cell growth via apoptosis. HPS increased the sub-G1 cell cycle fraction, with decreased expression of cyclins D1, D2, and E and their activating partners cdk2, cdk4, and cdk6, and a concomitant induction of p53 and p21/WAF1. Furthermore, HPS treatment increased the cytosolic level of cytochrome c and resulted in caspase-3 activation; this effect was correlated with Bax up-regulation and Bcl-2 down-regulation. Thus, these data suggest that HPS is a potential candidate for anti-cancer therapy in oral cancer.
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PMID:Anti-cancer activity of highly purified sulfur in immortalized and malignant human oral keratinocytes. 1792 Feb 32

Previous in vivo studies have suggested that lactobacilli can exert anti-proliferative effects on the gastric epithelium. However, few data are available on their mechanisms of action. The aim of this study was to investigate the effects of increasing concentrations of Lactobacillus rhamnosus strain GG (L. GG) homogenate on cell growth and proliferation [by 3-(4,5 di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, [(3)H]-thymidine incorporation and polyamine biosynthesis] and apoptosis processes (by Bax/Bcl-2 mRNA expression) in HGC-27 human gastric cancer cells. To verify which bacterial fraction was involved in the antiproliferative and proapoptotic effects, the cytoplasm and cell wall extracts were tested separately. HGC-27 cells were sensitive to the apoptotic induction and growth inhibition by increased concentrations of bacterial homogenate. HGC-27 cells were resistant to the bacterial cell wall fractions, whereas increasing cytoplasm fraction concentrations induced evident antiproliferative and proapoptotic actions. These data suggest that cytoplasm extracts could be responsible for L. GG action on HGC-27 cell proliferation.
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PMID:Effects of Lactobacillus rhamnosus GG on the cell growth and polyamine metabolism in HGC-27 human gastric cancer cells. 1792 9

Bcl-2 is overexpressed in a variety of human tumors and is involved in tumorigenesis and chemoresistance. In this study, we investigated the inhibitory effect of the hairpin Bcl-2 small interfering (si)RNA on the expression of the Bcl-2 gene in the cisplatin (DDP)-resistant human lung adenocarcinoma cell line A549/DDP, and the effect of Bcl-2 siRNA on drug sensitization in A549/DDP cells. Bcl-2 siRNA and negative siRNA plasmids were constructed and stably transfected into A549/DDP cells. Reverse transcription-polymerase chain reaction, immunofluorescence microscopy and Western blot analysis were used to detect the target gene expression. Spontaneous cell apoptosis was detected by acridine orange and ethidium bromide staining. Drug sensitivity of the cells to DDP and diallyl disulfide (DADS) was analyzed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. Expression levels of Bcl-2 mRNA and protein in siRNA stable transfectants were clearly reduced compared with negative siRNA transfectants and untreated cells. MTT results indicated that Bcl-2 transfectants had a higher cell inhibition rate after treatment with 0.2-200 microg/ml DDP or 50-200 microM DADS. Flow cytometry revealed increased apoptosis in Bcl-2 siRNA cells. After the addition of 20 microg/ml DDP or 100 microM DADS, siRNA targeting of the Bcl-2 gene specifically down-regulated gene expression in A549/DDP cells, increased spontaneous apoptosis, and sensitized cells to DDP and DADS.
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PMID:Bcl-2 small interfering RNA sensitizes cisplatin-resistant human lung adenocarcinoma A549/DDP cell to cisplatin and diallyl disulfide. 1798 74


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