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)

This study is to examine the effects of equol on the H(2)O(2)-induced death of bovine aortic endothelial cells (bAECs) and the mechanism of its protective effects. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] assay showed that in the control group, cell survival rate decreased significantly, each in proportion to the duration of the H(2)O(2) stimulation (P<0.05), but, in the equol-pretreated group, such decrease was not statistically significant. After Hoechst 33342 staining, in the equol-pretreated group the number of cells with apoptotic morphology decreased significantly. Equol pretreatment effectively inhibited the H(2)O(2)-induced cell death by the reduction of intracellular ROS production (P<0.05). Incubation of bAECs with equol increased the expression of phospho-p38 MAPK and Bcl-2 after the H(2)O(2) exposure compared with their expression without the equol pretreatment. Furthermore, SB203580 inhibited phospho-p38 MAPK expression and increased apoptotic cell death. This study proves equol has a significant antioxidant effect on the bAECs that were exposed to H(2)O(2).
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PMID:Antioxidant effects of equol on bovine aortic endothelial cells. 1870 29

In this study, we investigated the effects of continentalic acid (CA, (-)-pimara-8(14), 15-diene-19-oic acid), a diterpenic acid, isolated from Aralia continentalis, on the proliferation and apoptosis induction of HepG2 cells. In 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, the inhibitory effect became gradually stronger with the passage of time, 24, 48 and 72 h after treatment with CA, and the most significant effect was observed at 72 h. CA treatment for 72 h induced DNA fragmentation in a dose-dependent manner. Furthermore, flow cytometric analysis of HepG2 cells exposed to CA showed that apoptotic cells increased in a dose-dependent manner. The induction of apoptosis in HepG2 cells by CA was mediated through the activation of caspase-3, Bak, and Bax, and then through the cleavage of peroxisome proliferator-activated receptor (PARP) and the down-regulation of Bcl-2. These results demonstrate that CA efficiently induces apoptosis and is a good candidate for further evaluation as an effective chemotherapeutic agent.
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PMID:Continentalic acid from Aralia continentalis induces growth inhibition and apoptosis in HepG2 cells. 1880 61

Ubiquitin carboxy terminal hydrolase-L1 (UCH-L1) belongs to the UCH proteases family that deubiquitinates ubiquitin-protein conjugates in the ubiquitin-proteasome system. Previous research showed that UCH-L1 was expressed in mouse retinal cells and testicular germ cells, and its function was associated with apoptosis. But it is still unclear whether UCH-L1 is concerned with apoptosis in tumor cells. In order to clarify the role of UCH-L1 in tumor cells, multi-drug resistance (MDR) human breast carcinoma cell line MCF7/Adr, that expresses relatively high UCH-L1, and its parental cell line MCF7, that expresses relatively low UCH-L1, were chosen for this study. We transfected pcDNA3.1-UCH-L1 plasmid and UCH-L1 siRNA into MCF7 and MCF7/Adr cells, respectively. Using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, western blot, Hoechst 33258 staining assay and flow cytometry, we found that over-expression of UCH-L1 in MCF7 cells induced apoptosis. On the other hand, silencing of UCH-L1 in MCF7/Adr cells led to the opposite effect. Moreover, to explore the mechanism underling these observations, we further investigated the expression of phospho-Akt and its downstream signal phospho-IkB-alpha and other signal molecules including Fas, Fas-L, Trail, DR4, DR5, Bax, cytochrome C, active caspase-3, phospho-p53, phospho-Mdm-2, Bcl-2, Bcl-xL, p21 and p27. The results indicated that the process of apoptosis triggered by UCH-L1 is, at least in part, probably through Phosphoinositide 3-kinase (PI3K)/Akt signal pathway. Our findings suggest that modulating the ubiquitination and deubiquitination pathway could be a novel method for tumor therapy.
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PMID:Over-expression of ubiquitin carboxy terminal hydrolase-L1 induces apoptosis in breast cancer cells. 1894 67

Exposure to various toxicants is known to cause apoptosis in various cell types. The spermatogenic cells are particularly sensitive to various deleterious conditions including toxicant exposure. The affected cells might undergo apoptosis; however, the mechanisms may be different for different kinds of insults to the cells. In the present study, we looked into the mechanisms involved in apoptosis after exposure of testicular cells from mice to two different chemicals, diethyl maleate (DEM) and tert-butyl hydroperoxide (TBHP). For the study, cells were maintained for 4 h under various treatments: control (media only), 0.25 mM DEM, 0.5 mM DEM, 0.25 mM TBHP, and 0.5 mM TBHP. The treated cells were then harvested for various estimations, viz. viability, reduced and oxidized glutathione, redox ratio, free radical generation, and ethidium bromide/acridine orange co-staining. mRNA was extracted for RT-PCR analysis of Caspase 3, Caspase 8, Caspase 9, p53, p21, Bax, and Bcl-2. It was observed that both the treatments resulted in decreased levels of reduced glutathione and a concomitant increase in the oxidized form and ROS levels in a dose-dependent manner. The apoptotic cell death was evident from ethidium bromide/acridine orange staining. The mRNA expression pattern of various Caspases showed progressive increase in Caspase 3 and Caspase 9 mRNA in both the treatments in a dose-dependent manner, whereas there was no change in Caspase 8 mRNA expression. p53, p21, and Bax also showed increased expression, whereas Bcl-2 expression remained unchanged in DEM treatments and increased significantly in both TBHP treatments. Hence, the present study indicates the involvement and activation of various apoptotic factors, particularly Caspase 3 and 9 along with p53, in response to exposure of testicular cells to DEM and TBHP.
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PMID:Regulation of apoptosis by Caspases under oxidative stress conditions in mice testicular cells: in vitro molecular mechanism. 1897 86

Guattegaumerine is a natural product with characteristics of being lipophilic and reaching high concentration in the brain, but its function in the central nervous system has not yet been observed. This study was designed to evaluate the neuroprotective effects of guattegaumerine on rat primary cultured cortical neurons. Following a 24-h exposure of the cells to combined serum-starvation and hydrogen peroxide, a significant augment in neuron damage as determined by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) release were observed. Preincubation of guattegaumerine dramatically improved the cell viability and inhibited LDH release. Preincubation of guattegaumerine also dramatically inhibited malondialhehyde (MDA) production and elevated the decreased total antioxidative capacity in cells caused by the combined injury. Results of flow cytometry and immunohistochemistry showed that pre-addition of guattegaumerine interrupted the apoptosis of the neurons, reversed the up regulation of the pro-apoptotic gene (Bax) and the down regulation of the anti-apoptotic gene (Bcl-2). Furthermore, guattegaumerine suppressed the increase of intracellular calcium ([Ca(2+)](i)) stimulated by either H(2)O(2) or KCl in Ca(2+)-containing extracellular solutions, and high concentration of 2.5 microM guattegaumerine also suppressed the increase of [Ca(2+)](i) induced by H(2)O(2) in Ca(2+)-free solution. These observations suggested that guattegaumerine may possess potential protection against oxidative stress injury, which might be beneficial for neurons.
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PMID:Guattegaumerine protects primary cultured cortical neurons against oxidative stress injury induced by hydrogen peroxide concomitant with serum deprivation. 1901 76

In this study, cationic nanoparticles self-assembled from the amphiphilic copolymer poly(N-methyldietheneamine sebacate)-co-[(cholesteryl oxocarbonylamido ethyl) methyl bis(ethylene) ammonium bromide] sebacate) (P(MDS-co-CES) were synthesized and used to deliver Bcl-2 targeted siRNA into HepG2, HeLa and MDA-MB-231 cell lines, and downregulate Bcl-2 mRNA expression levels. Confocal microscopic studies show that the nanoparticles were able to complex with siRNA and deliver it inside the cells efficiently, but siRNA was easily dissociated from the complexes in the cytoplasm for its biological functions. Bcl-2 mRNA expression levels as low as 10% were achieved after treatment with nanoparticle/siRNA complexes. The downregulation efficiency of Bcl-2 mRNA level was similar to that mediated by Lipofectamine but higher than that induced by PEI. PEG was also conjugated to siRNA via a cleavable disulfide bond, and nanoparticle/siRNA-PEG complexes showed no significant protein adsorption as compared with 26 and 17% for blank nanoparticles and nanoparticle/siRNA complexes, respectively. The presence of serum caused slight aggregation of nanoparticle/siRNA or nanoparticle/siRNA-PEG complexes. However, the size of the complexes was still below 250 nm after being incubated in PBS containing 10% serum for 4 h. On the other hand, PEGylated siRNA delivered by the nanoparticles downregulated Bcl-2 mRNA expression level in the cells as efficiently as unmodified siRNA. Bcl-2 protein was also downregulated efficiently by nanoparticle/siRNA complexes in all cell lines tested. The downregulation of Bcl-2 mRNA or Bcl-2 protein did not show significant cell death in the tested siRNA and polymer concentration range. However, the delivery of siRNA sensitized HeLa cells to paclitaxel treatment, yielding significant improvement over the untreated cells (p<0.05). These cationic nanoparticles may be potentially employed to downregulate Bcl-2 expression and sensitize cancer cells to anticancer drugs for more efficient chemotherapy.
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PMID:Efficient delivery of Bcl-2-targeted siRNA using cationic polymer nanoparticles: downregulating mRNA expression level and sensitizing cancer cells to anticancer drug. 1907 31

In view of the controversial role of catalytic activity on the cytotoxicity of phospholipase A(2) (PLA(2)), the present study is conducted to explore whether PLA(2) induces apoptotic process of human leukemia U937 cells through catalytic activity-independent pathway. Modification of His-48 (according to the sequence alignment with porcine pancreatic PLA(2)) with p-bromophenacyl bromide (BPB) caused over 99.9% drop in enzymatic activity Naja naja atra PLA(2). It was found that BPB-PLA(2)-induced apoptotic death of U937 cells was associated with mitochondrial depolarization, modulation of Bcl-2 family members, cytochrome c release and activation of caspases 9 and 3. Upon exposure to BPB-PLA(2), elevation of intracellular Ca(2+) levels and p38 MAPK activation were observed in U937 cells. Pretreatment with BAPTA-AM (Ca(2+) chelator) and nifedipine (L-type Ca(2+) channel blocker) abrogated Ca(2+) increase and p38 MAPK activation, and rescued viability of BPB-PLA(2)-treated U937 cells. BPB-PLA(2)-induced dissipation of mitochondrial membrane potential and down-regulation of Bcl-2 were suppressed by SB202190 (p38MAPK inhibitor). Although PLA(2) mutants in which His-48 and Asp-49 were substituted by Ala and Lys, respectively, did not display detectable PLA(2) activity, they induced death of U937 cells. The signaling pathway of PLA(2) mutants in inducing cell death was indistinguishable from that of BPB-PLA(2). Taken together, our data indicate that catalytic activity-independent pathway is involved in PLA(2)-induced apoptotic death of human leukemia U937 cells via mitochondria-mediated death pathway triggering by Ca(2+)-mediated p38 MAPK activation.
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PMID:Catalytic activity-independent pathway is involved in phospholipase A(2)-induced apoptotic death of human leukemia U937 cells via Ca(2+)-mediated p38 MAPK activation and mitochondrial depolarization. 1911 7

Liquiritigenin is a flavanone existed in Radix glycyrrhizae. The objective of this study is to explore the effects of liquiritigenin on SMMC-7721 cells and its possible mechanism. The viability of liquiritigenin treat cells was decreased in a dose-dependent manner assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylterazolium bromide (MTT), and apoptotic morphological changes also be observed, such as chromatin condensation and nuclear fragmentation. Assessment of apoptotic cells by flow cytometry indicated that cells fell into apoptosis after 0.4mM liquiritigenin treatment. In addition, a concomitant time-dependent increase in caspase-3 activity was also observed. The level of p53 protein increased and Bcl-2 protein decreased time-dependently. Further studies found the induction of apoptosis by liquiritigenin was accompanied with the production of reactive oxygen species (ROS), disruption of mitochondrial membrane potential and depletion of antioxidant enzymes. The significant ROS generation was firstly found at 3h and being time-dependent until 9h. A time-dependent decrease in membrane potential occurred, and significant loss appeared at 9h and 12h. Furthermore, pretreatment of N-acetyl-cysteine (NAC), ROS production and apoptosis induced by liquiritigenin were both suppressed. In sum, this paper indicated the cytotoxicity of liquiritigenin on SMMC-7721 cells may via effect on generation of ROS, later lead to cell apoptosis.
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PMID:Effect of liquiritigenin, a flavanone existed from Radix glycyrrhizae on pro-apoptotic in SMMC-7721 cells. 1915 Mar 83

The Bcl-2 family of proteins is critical to the life and death of malignant B-lymphocytes. Interfering with their activity using small-molecule inhibitors (SMI) is being explored as a new therapeutic strategy for treating B-cell tumors. We evaluated the efficacy of TW-37, a non-peptidic SMI of Bcl-2 against a range spectrum of human B-cell lines, fresh patient samples and animal xenograft models. Multiple cytochemical and molecular approaches such as acridine orange/ethidium bromide assay for apoptosis, co-immunoprecipitation of complexes and western blot analysis, caspase luminescent activity assay and apoptotic DNA fragmentation assay were used to demonstrate the effect of TW-37 on different B-cell lines, patient derived samples, as well as in animal xenograft models. Nanomolar concentrations of TW-37 were able to induce apoptosis in both fresh samples and established cell lines with IC50 in most cases of 165-320 nM. Apoptosis was independent of proliferative status or pathological classification of B-cell tumor. TW-37 was able to block Bim-Bcl-XL and Bim-Mcl-1 heterodimerization and induced apoptosis via activation of caspases -9, -3, PARP and DNA fragmentation. TW-37 administered to tumor-bearing SCID mice led to significant tumor growth inhibition (T/C), tumor growth delay (T-C) and Log10kill, when used at its maximum tolerated dose (40 mg/kg x 3 days) via tail vein. TW-37 failed to induce changes in the Bcl-2 proteins levels suggesting that assessment of baseline Bcl-2 family proteins can be used to predict response to the drug. These findings indicate activity of TW-37 across the spectrum of human B-cell tumors and support the concept of targeting the Bcl-2 system as a therapeutic strategy regardless of the stage of B-cell differentiation.
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PMID:SMI of Bcl-2 TW-37 is active across a spectrum of B-cell tumors irrespective of their proliferative and differentiation status. 1922 Aug 84

This study examined the mechanism by which the gastric cancer cells lead to early peritoneal metastasis. HMrSV5 cells, a human peritoneal mesothelial cell line, were co-incubated with the supernatants of gastric cancer cells. Morphological changes of HMrSV5 cells were observed. The cell damage was quantitatively determined by MTT assay. The apoptosis of HMrSV5 cells was observed under transmission electron microscope. Acridine orange/ethidium bromide-stained condensed nuclei was detected by fluorescent microscopy and flow cytometry. The expressions of Bcl-2 and Bax was immunochemically evaluated. The results showed that conspicuous morphological changes of apoptosis were observed in HMrSV5 cells 24 h after treatment with the supernatants of gastric cancer cells. The supernatants could induce apoptosis of HMrSV5 cells in a time-dependent manner. The supernatants could up-regulate the expression of Bax and suppress that of Bcl-2 in HMrSV5 cells. These findings demonstrated that gastric cancer cells can induce the apoptosis of HPMCs through supernatants in the early peritoneal metastasis. The abnormal expressions of Bcl-2 and Bax may contribute to the apoptosis. Anti-apoptosis drugs promise to be adjuvant chemotherapeutic agents in the treatment of peritoneal metastasis of gastric cancer.
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PMID:Destruction of gastric cancer cells to mesothelial cells by apoptosis in the early peritoneal metastasis. 1939 97


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