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: EC:3.4.22.61 (caspase-8)
6,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cell survival activity of human glioma cells is largely dependent on autocrine fibroblast growth factor (FGF) signaling. Caspases, a family of cysteine proteases, play an integral part in the execution phase of apoptosis. To better understand the mechanism of resistance to apoptosis in human glioma cells, we investigated the effect of a blockade of endogenous FGF signaling through the expression of the dominant negative type I FGF receptor (DNFGFR) in U251MG cells. The cells were infected with adenovirus vector expressing DNFGFR (AdDNFGFR) and apoptosis was semi-quantified by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method and flow cytometric annexin V assay. The activation of caspase-3, -8, and -9, the activation of Akt, a serine/threonine protein kinase, and the cleavage of poly(ADP-ribose) polymerase (PARP) were analyzed by immunoblotting. The infection with AdDNFGFR (multiplicity of infection of 200) induced marked apoptosis, along with a down-regulation of akt phosphorylation, and activation of caspase-9 and -3, but not -8. By contrast, LacZ virus (a control) had minimal effects. The level of the cleaved form of PARP was increased in a time-dependent fashion, and this increase was inhibited by adding Z-DEVD-FMK, a caspase-3 inhibitor, and Z-LEHD-FMK, a caspase-9 inhibitor. Moreover, ultraviolet exposure (100 J/m(2)) induced apoptosis and caspase-8, but not caspase-9, activation. Our data suggested that the induction of apoptosis through the inhibition of endogenous FGF signaling is caspase-9 pathway- dependent. The suppression of this or other specific anti-apoptotic pathways may lead to genetic or pharmacological manipulations that favorably modulate the malignant behavior of human gliomas.
...
PMID:Caspase-9 pathway activation by inhibiting endogenous fibroblast growth factor signaling in human glioma cells. 1820 70

The cellular Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitory protein-long form (c-FLIP(L)) is a key regulator of Fas signaling, although owing a dominant-negative homologue of caspase-8, the role of c-FLIP(L) remains controversial. In the present study, two pairs of small interfering RNA (siRNA) directed against c-FLIP(L) were used to assess the effect of c-FLIP(L) on Fas-mediated apoptosis of colon carcinoma in vitro. HT-29 cell line was selected for overexpression of c-FLIP(L) and Fas with RT-PCR and flow cytometry analyses. After electroporation, the mRNA level of c-FLIP(L) was significantly decreased (control siRNA versus c-FLIP(L) siRNA, 77.97+/-5.61% versus 26.22+/-3.79%) and the maximum interfering efficiency was around 66.49% using semi-quantitative RT-PCR analysis. Knockdown of c-FLIP(L) with the specific siRNA sensitized colon carcinoma cells to Fas-mediated apoptosis (control siRNA versus c-FLIP(L) siRNA, 5.68+/-2.11% versus 29.50+/-2.27%) using DNA content analysis and Annexin V-FITC analysis. In conclusion, our study indicated that c-FLIP(L) might be a suppressor of Fas-mediated apoptosis in Fas antigen expressing colon carcinoma and therefore a potential target for novel anticancer therapies.
...
PMID:Critical role for c-FLIP(L) on Fas resistance in colon carcinoma cell line HT-29. 1824 39

Betanodavirus protein alpha induces cell apoptosis or secondary necrosis by a poorly understood process. In the present work, red spotted grouper nervous necrosis virus (RGNNV) RNA 2 was cloned and transfected into tissue culture cells (GF-1) which then underwent apoptosis or post-apoptotic necrosis. In the early apoptotic stage, progressive phosphatidylserine externalization was evident at 24h post-transfection (p.t.) by Annexin V-FLUOS staining. TUNEL assay revealed apoptotic cells at 24-72 h p.t, after which post-apoptotic necrotic cells were identified by acridine orange/ethidium bromide dual dye staining from 48 to 72 h p.t. Protein alpha induced progressive loss of mitochondrial membrane potential (MMP) which was detected in RNA2-transfected GF-1 cells at 24, 48, and 72 h p.t., which correlated with cytochrome c release, especially at 72 h p.t. To assess the effect of zfBcl-xL on cell death, RNA2-transfected cells were co-transfected with zfBcl-x(L). Co-transfection of GF-1 cells prevented loss of MMP at 24 h and 48 h p.t. and blocked initiator caspase-8 and effector caspase-3 activation at 48 h p.t. We conclude that RGNNV protein alpha induces apoptosis followed by secondary necrotic cell death through a mitochondria-mediated death pathway and activation of caspases-8 and -3.
...
PMID:Zebrafish anti-apoptotic protein zfBcl-xL can block betanodavirus protein alpha-induced mitochondria-mediated secondary necrosis cell death. 1827 61

OX40, a member of the tumor necrosis factor receptor (TNF-R) superfamily, has been shown to play an important role in the survival of antigen-specific CD4(+) T cells. We have previously reported that stimulation of the OX40-expressing and HIV-1 chronically infected T cell line, ACH-2/OX40, with either OX40 ligand (OX40L)-expressing cells or with TNF resulted in the activation of HIV-1 followed by apoptotic cell death. In the present study we found that costimulation via OX40 and TNF-R in OX40-expressing HIV-1-infected T cell lines leads to a marked reduction of HIV-1 production associated with rapid cell death. Since HIV-1-negative OX40(+) T cell lines underwent rapid apoptotic cell death after OX40L and TNF stimulation, it was reasoned that the ACH-2/OX40 cell death was unlikely to be due to HIV-1 infection. Furthermore, we found that the OX40-mediated apoptosis of the CD4(+) T cell line, Molt-4/CCR5-OX40 (M/R5-OX40), required (1) signals mediated via the cytoplasmic tail of OX40, (2) activation of the caspase cascade, including caspase-8 and caspase-3, and (3) induction of endogenous TNF-alpha, but not of TNF-beta, FasL, or TNF-related apoptosis-inducing ligand (TRAIL), suggesting that this apoptosis occurred indirectly via the TNF/TNF-R system. Finally, a fraction of primary activated CD4(+) T cells, expressing high levels of OX40, underwent apoptosis, as revealed by annexin V staining, after cocultivation with OX40L(+) cells. These results suggest a new biological role of the OX40L/OX40 system in controlling the fate of activated CD4(+) T cells and of controlling HIV-1 infection in inflammatory environments.
...
PMID:Enhancement of OX40-induced apoptosis by TNF coactivation in OX40-expressing T cell lines in vitro leading to decreased targets for HIV type 1 production. 1832 75

A quaternary benzo[c]phenanthridine alkaloid chelerythrine displays a wide range of biological activities including cytotoxicity to normal and cancer cells. In contrast, less is known about the biological activity of dihydrochelerythrine, a product of chelerythrine reduction. We examined the cytotoxicity of chelerythrine and dihydrochelerythrine in human promyelocytic leukemia HL-60 cells. After 4h of treatment, chelerythrine induced a dose-dependent decrease in the cell viability with IC50 of 2.6 microM as shown by MTT reduction assay. Dihydrochelerythrine appeared to be less cytotoxic since the viability of cells exposed to 20 microM dihydrochelerythrine for 24h was reduced only to 53%. Decrease in the viability induced by both alkaloids was accompanied by apoptotic events including the dissipation of mitochondrial membrane potential, activation of caspase-9 and -3, and appearance of cells with sub-G1 DNA. Moreover, chelerythrine, but not dihydrochelerythrine, elevated the activity of caspase-8. A dose-dependent induction of apoptosis and necrosis by chelerythrine and dihydrochelerythrine was confirmed by annexin V/propidium iodide dual staining flow cytometry. Besides, both alkaloids were found to induce accumulation of HL-60 cells in G1 phase of the cell cycle. We conclude that both chelerythrine and dihydrochelerythrine affect cell cycle distribution, activate mitochondrial apoptotic pathway, and induce apoptosis and necrosis in HL-60 cells.
...
PMID:Chelerythrine and dihydrochelerythrine induce G1 phase arrest and bimodal cell death in human leukemia HL-60 cells. 1835 94

Combined treatment with quercetin and TRAIL induced cytotoxicity and enhanced annexin V staining and poly (ADP-ribose) polymerase (PARP) cleavage in human prostate cancer cell lines DU-145 and PC-3. These indicators of apoptosis resulted from the activation of caspase-8, -9, and -3. Although the expression levels of FLIPs, cIAP1, cIAP2, and the Bcl-2 family were not changed in quercetin-treated cells, significant downregulation of survivin occurred. Knockdown survivin by siRNA significantly increased TRAIL-induced apoptosis. We hypothesized that quercetin-induced activation of MAPK (ERK, p38, JNK) is responsible for downregulation of survivin gene expression. To test this hypothesis, we selectively inhibited MAPK during treatment with quercetin. Our data demonstrated that inhibitor of ERK (PD98059), but not p38 MAPK (SB203580) or JNK (SP600125), significantly maintained the intracellular level of survivin during treatment with quercetin. Interestingly, PD98059 also prevented quercetin-induced deacetylation of histone H3. Data from survivin promoter activity assay suggest that the Sp1 transcription factor binds to the survivin promoter region and quercetin inhibits its binding activity through deacetylation of histone H3. Quercetin-induced activation of the ERK-MSK1 signal transduction pathway may be responsible for deacetylation of histone H3. Taken together, our findings suggest that quercetin enhances TRAIL induced apoptosis by inhibition of survivin expression, through ERK-MSK1-mediated deacetylation of H3.
...
PMID:Quercetin augments TRAIL-induced apoptotic death: involvement of the ERK signal transduction pathway. 1837 72

The mechanism of antitumor action of a synthetic nitroflavone derivative, 2'-nitroflavone, was evaluated in vitro in HeLa human cervix adenocarcinoma cells. We showed that the nitroflavone derivative slowed down the cell cycle at the S phase and increase the population of cells at the G2/M phase after 24h of incubation. The treatment with 2'-nitroflavone also induced an apoptotic response, characterized by an increase of the sub-G1 fraction of cells, by cells with chromatin condensation and membrane blebbing, by a typical ladder of DNA fragmentation and by detection of apoptotic cells stained with Annexin V. The observed apoptosis was regulated by caspase-8 and -9, both contributing to the activation of the effector caspase-3. In addition, inhibitors of caspase-8 or -9 partially protected HeLa cells from 2'-nitroflavone-induced cell death. We also found that 2'-nitroflavone did not affect the total amount of Bax and Bcl-2 proteins, although a translocation of Bax from cytosol to mitochondria was evident after 6h of exposure. Furthermore, 2'-nitroflavone decreased the expression of the anti-apoptotic Bcl-XL protein, induced the release of cytochrome C to cytosol and increased the levels of Fas and Fas-L. Our results indicated that both death receptor and mitochondria-dependent pathways are involved in the apoptotic cell death triggered by 2'-nitroflavone and suggest that this derivative could be a potentially useful agent for the treatment of certain malignancies.
...
PMID:2'-Nitroflavone induces cell cycle arrest and apoptosis in HeLa human cervical carcinoma cells. 1848 87

Recent evidence suggests oxygen as a powerful trigger for cell death in the immature white matter, leading to periventricular leukomalacia (PVL) as a cause of adverse neurological outcome in survivors of preterm birth. This oligodendrocyte (OL) death is associated with oxidative stress, upregulation of apoptotic signaling factors (i.e., Fas, caspase-3) and decreased amounts of neurotrophins. In search of neuroprotective strategies we investigated whether the polysulfonated urea derivative suramin, recently identified as a potent inhibitor of Fas signaling, affords neuroprotection in an in vitro model of hyperoxia-induced injury to immature oligodendrocytes. Immature OLs (OLN-93) were subjected to 80% hyperoxia (48 h) in the presence or absence of suramin (0, 30, 60, 120 microM). Cell death was assessed by flow cytometry (Annexin V, caspase-3 activity assay) and immunohistochemistry for activated caspase-3. Immunoblotting for the death receptor Fas, cleaved caspase-8 and the phosphorylated isoform of the serine-threonin kinase Akt (pAkt) was performed. Suramin lead to OL apoptosis and potentiated hyperoxia-induced injury in a dose-dependent manner. Immunoblotting revealed increased Fas and caspase-8 expression by suramin treatment. This effect was significantly enhanced when suramin was combined with hyperoxia. Furthermore, pAkt levels decreased following suramin exposure, indicating interference with neurotrophin-dependent growth factor signaling. These data indicate that suramin causes apoptotic cell death and aggravates hyperoxia-induced cell death in immature OLs. Its mechanism of action includes an increase of previously described hyperoxia-induced expression of pro-apoptotic factors and deprivation of growth factor dependent signaling components.
...
PMID:Suramin induces and enhances apoptosis in a model of hyperoxia-induced oligodendrocyte injury. 1852 99

To investigate the combined effect of human recombinant soluble TNF-related apoptosis induced ligand (hrsTRAIL) with Ara-C or alone on HL-60 leukemia cell lines and its mechanism, human leukemia cell lines HL-60 were cultured in vitro. HL-60 cells were divided into 5 groups: control group, Ara-C group, rsTRAIL group, Ara-C + rsTRAIL simultaneously given group, Ara-C + rsTRAIL tandem given group (Ara-C followed by rsTRAIL group). The cytotoxic effect was measured by MTT assay; cell apoptosis rate was determined by flow cytometry after Annexin V/PI staining; the expression level of DR5 on surface of HL-60 cells treated with Ara-C at different concentrations for 24 hours was determined by flow cytometry. The expression level of DR5 on surface of HL-60 cells and caspase-8 activity in HL-60 cells of rsTRAIL group and Ara-C + rsTRAIL tandem group was determined by flow cytometry. The result showed that rsTRAIL could inhibit the proliferation of HL-60 cells and induce apoptosis of HL-60 cells in a concentration-dependent manner. The apoptosis rate of HL-60 cells in Ara-C + rsTRAIL tandem given group was higher than that in Ara-C + rsTRAIL simultaneously given group, the expression level of DR5 on surface of HL-60 cells and intracellular activity of caspase-8 in Ara-C + rsTRAIL tandem given group were higher than those in rsTRAIL group. When HL-60 cells treated with 5 and 10 mg/L of Ara-C for 24 hours, the expression level of DR5 on surface of HL-60 cells was higher than that in control group. It is concluded that rsTRAIL can inhibit the proliferation of HL-60 cells, and induce apoptosis of HL-60 cells. Ara-C can upregulate DR5 expression on the surface of HL-60 cells and enhance the effect of rsTRAIL-inducing apoptosis. Tandem treatment of HL-60 cells with Ara-C followed by rsTRAIL induce more apoptosis than that of co-treatment with rsTRAIL and Ara-C. Ara-C and rsTRAIL has a synergistic inhibitory effect on growth of HL-60 cells. The mechanism may correlate with up-regulation of the expression level of DR5 and/or caspase-8 in HL-60 cells by Ara-C.
...
PMID:[Combined effect of TNF-related apoptosis induced ligand and Ara-C in inducing apoptosis of HL-60 cells and its mechanism]. 1854 19

AMAD, an emodin azide methyl anthraquinone derivative, was extracted from the nature giant knotweed rhizome of traditional Chinese herbs. Here, we investigated the anticancer activities and signaling pathways implicated in AMAD-induced apoptosis in human breast cancer cell lines MDA-MB-453 and human lung adenocarcinoma Calu-3 cells. AMAD was found to have a potent cytotoxic effect on both cell lines. Hoechst 33258 staining and Annexin V/propidium iodide double staining exhibited the typical nuclear features of apoptosis and increased the proportion of apoptotic Annexin V-positive cells in a dose-dependent manner, respectively. Moreover, this apoptotic induction was associated with a collapse of the mitochondrial membrane potential and activated caspases (cysteine aspartase) cascade involving in caspase-8, caspase-9, caspase-3, and poly(ADP-ribose) polymerase cleavage in a concentration-dependent manner. It was noteworthy that AMAD also effectively cleaved Bid, a BH3 domain-containing proapoptotic Bcl-2 family member, and induced the subsequent release of cytochrome c from mitochondria into the cytosol. Furthermore, suppression of caspase-8 activity with Z-IETD-FMK partially inhibited release of cytochrome c and Bid cleavage induced by AMAD, whereas exposure to Z-LETD-FMK, a caspase-9 inhibitor, had no effect. Additionally, there was significant change in other mitochondrial membrane proteins triggered by AMAD, such as Bcl-xl and Bad. It was intriguing that AMAD decreased the generation of reactive oxygen species in both cell lines. DNA-binding assay exhibited apoptosis induced by AMAD was not involved in intercalating to DNA. Taken together, these data suggested that AMAD induced apoptosis via a mitochondrial pathway involving caspase-8/Bid activation in both cell lines.
...
PMID:Emodin azide methyl anthraquinone derivative triggers mitochondrial-dependent cell apoptosis involving in caspase-8-mediated Bid cleavage. 1856 40


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

---