Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hexabromocyclododecane (HBCD) is widely used as a brominated flame retardant, and has been detected in the aquatic environment, wild animals, and humans. However, details of the environmental health risk of HBCD are not well known. In this study, zebrafish embryos were used to assess the developmental toxicity of the chemical. Four-hour post-fertilization (hpf) zebrafish embryos were exposed to various concentrations of HBCD (0, 0.05, 0.1, 0.5, and 1.0 mg L(-1)) until 96 h. Exposure to 0.1, 0.5, and 1.0 mg L(-1) HBCD significantly increased the malformation rate and reduced survival in the 0.5 and 1.0 mg L(-1) HBCD exposure groups. Acridine orange (AO) staining showed that HBCD exposure resulted in cell apoptosis. Reactive oxygen species (ROS) was significantly induced at exposures of 0.1, 0.5, and 1.0 mg L(-1) HBCD. To test the apoptotic pathway, several genes related to cell apoptosis, such as p53, Puma, Apaf-1, caspase-9, and caspase-3, were examined using real-time PCR. The expression patterns of these genes were up-regulated to some extent. Two anti-apoptotic genes, Mdm2 (antagonist of p53) and Bcl-2 (inhibitor of Bax), were down-regulated, and the activity of capspase-9 and caspase-3 was significantly increased. The overall results demonstrate that waterborne HBCD is able to produce oxidative stress and induce apoptosis through the involvement of caspases in zebrafish embryos. The results also indicate that zebrafish embryos can serve as a reliable model for the developmental toxicity of HBCD.
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PMID:Hexabromocyclododecane-induced developmental toxicity and apoptosis in zebrafish embryos. 1935 5

The effects of simulated orthodontic forces such as centrifugal force or water pressure on sodium fluoride (NaF)-induced cytotoxicity against mouse osteoblast-like cells MC3T3-E1 were investigated. Loading with centrifugal force (44.5 g/cm2) or water pressure (5 g/cm2) slightly reduced the cell proliferation and additively enhanced the cytotoxic activity of millimolar concentrations of NaF. NaF induced the appearance of phosphatidylserine at outer cell membrane (detected by Annexin staining) but failed to induce caspase-3 activation even under the water pressure. On the other hand, NaF induced autophagic phenotype characterized by the formation of acidic organelles (detected by acridine orange staining). NaF did not increase, but rather dose-dependently reduced the alkaline phosphatase activity, with or without the loading of water pressure. The present study demonstrates that centrifugal force and water pressure partially enhanced the caspase-independent cytotoxicity of NaF against osteoblasts. These simulated orthodontic forces may be a new factor that affects the physiological activity of NaF.
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PMID:Effect of simulated orthodontic forces on fluoride-induced cytotoxicity in MC3T3-E1 osteoblast-like cells. 1941 11

Beta-sitosterol is an important phytosterol found in plant food. It has been shown to have antiproliferative effects on cancers of the colon, breast, and prostate, but its effect on stomach cancer cells in vitro is unknown. Proliferation, cytotoxicity, and apoptosis in SGC-7901 human stomach cancer cells were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, clone formation, lactate dehydrogenase (LDH) leakage assay, acridine orange (AO)/ethidium bromide (EB) double staining, 4',6-diamidine-2'-phenylindole dihydrochloride (DAPI) staining, comet assay, and Western blotting. The results showed that beta-sitosterol suppresses the proliferation and induces the cell cytotoxicity of SGC-7901 stomach cancer cells in a time- and dose-dependent manner. Cells treated with different concentrations of beta-sitosterol also showed changes typical of apoptosis: morphological changes, DNA damage, increased expression of pro-caspase-3 and bax (p < 0.05), and activation of pro-caspase-3 and suppression of bcl-2 expression (p < 0.05). This study therefore revealed that beta-sitosterol significantly inhibits the growth and induces the apoptosis of SGC-7901 human stomach cancer cells in vitro. The decrease of the bcl-2/bax ratio and DNA damage may be the critical mechanisms of apoptosis induced by beta-sitosterol in SGC-7901 human stomach cancer cells.
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PMID:Beta-sitosterol inhibits cell growth and induces apoptosis in SGC-7901 human stomach cancer cells. 1945 33

Arsenic trioxide, As(2)O(3), has successfully been used to treat acute promyelocytic leukemia (APL). Induction of apoptosis in cancerous cells has been proposed to be the underlying mechanism for the therapeutic efficacy of arsenic. To further understand the cytotoxicity of arsenic compounds in APL cells, HL-60 cells were exposed to graded concentrations of the following arsenicals for up to 48 h: arsenic trioxide (As(III)), sodium arsenate (As(V)), phenylarsine oxide (PAO(III)), monomethylarsonous acid (MMA(III)), monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)), and the viability and modes of cell death assessed. The arsenic-exposed cells were stained with annexin V-PE and 7-aminoactinomycin D (7-AAD) and analyzed by flow cytometry in order to detect apoptotic and viable cells while cell morphology was visualized using scanning and transmission electron microscopy. Acridine orange staining and microtubule-associated protein 1 light chain 3 (MAP-LC3) detection were used to recognize autophagic cell death. The results showed that the compounds reduced viable HL-60 cells by inducing apoptosis in a concentration-dependent manner. None of the compounds tested caused a significant change in binding of acridine orange or redistribution of MAP-LC3. Potencies of the six different arsenic compounds tested were ranked as PAO(III)>MMA(III)> or =As(III)>As(V)>MMA(V)>DMA(V). An increase in caspase-3 activity by PAO(III), MMA(III) and DMA(V) implied that these compounds induced apoptosis in HL-60 cells through a caspase-dependent mechanism, but the other arsenic compounds failed to activate caspase-3, suggesting that they induce apoptosis by an alternative pathway.
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PMID:Differential cytotoxic effects of arsenic compounds in human acute promyelocytic leukemia cells. 1946 42

Quercetin, a widely distributed bioflavonoid, has been shown to induce growth inhibition in a variety of human cancer cells. However, the regulation of survivin and Bcl-2 on the quercetin-induced cell-growth inhibition and apoptosis in cancer cells remains unclear. In the present study, we report that quercetin can inhibit proliferation and induce apoptosis in HepG2 cells in dose- and time-dependent manner. Hoechst 33258 and acridine orange/ethidium bromide (AO/EB) staining showed that HepG2 cells underwent the typical morphologic changes of apoptosis characterized by nuclear shrinkage, chromatin condensation, or fragmentation after exposure to quercetin. Cell-cycle analysis reveals a significant increase of the proportion of cells in G(0)/G(1) phase. We also demonstrate that the levels of survivin and Bcl-2 protein expression in HepG2 cells decreased concurrently, and the levels of p53 protein increased significantly after treatment with quercetin by immunocytochemistry analysis. Relative activity of caspase-3 and caspase-9 increased significantly. These data clearly indicate that quercetin-induced apoptosis is associated with caspase activation, and the levels of survivin and Bcl-2. Our results indicate that the expression of survivin may be associated with Bcl-2 expression, and the inhibition expression of survivin, in conjunction with Bcl-2, might cause more pronounced apoptotic effects. Together, concurrent down-regulated survivin and Bcl-2 play an important role in HepG2 cell apoptosis induced by quercetin.
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PMID:Regulation of survivin and Bcl-2 in HepG2 cell apoptosis induced by quercetin. 1962 60

The tumor-specific cytotoxicity and the type of cell death induced by thirty-eight newly synthesized tetrahydroisoquinoline derivatives in human oral squamous cell carcinoma cell lines were investigated. 6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)(3,4-dimethoxyphenyl) methanone that has bulky substituents (such as 3,4-dimethoxybenzoyl group) (TQ9) and ethyl 2-benzyloxycarbonyl-1,2,3,4-tetrahydroisoquinoline-1-carboxylate that has ethoxycarbonyl group and benzyloxycarbonyl group (TD13) showed the highest tumor-specific cytotoxicity (TS=12.5 and 5.3, respectively). This supports the importance of molecular size for the cytotoxicity induction. TQ9 induced internulceosomal DNA fragmentation and caspase-3 activation only marginally in HL-60 cells, whereas it enhanced the formation of acidic organelles (stained with acridine orange) without induction of DNA fragmentation or caspase-3 activation in human squamous cell carcinoma cell lines (HSC-2, HSC-4), suggesting the induction of autophagy in the latter cells.
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PMID:Tumor-specific cytotoxic activity of 1,2,3,4-tetrahydroisoquinoline derivatives against human oral squamous cell carcinoma cell lines. 1966 19

The modulation of CD40L activity might represent a promising therapeutic target to reduce monocyte inflammatory functions in chronic diseases, such as rheumatoid arthritis. In the present study, we investigated the possible influence of nonsteroidal anti-inflammatory drugs (NSAIDs) on CD40L-induced monocyte survival. Monocytes were isolated from buffy coats by using Ficoll-Percoll gradients. Monocyte apoptosis was evaluated by fluorescence microscopy on cytopreps stained with acridine orange or using flow cytometry analysis of Annexin-V and Propidium Iodide staining. Akt and NF-kappaB activation was assessed using western blot. Caspase 3 activity was determined spectrophotometrically. Among different NSAIDs, only oxaprozin dose-dependently increased apoptosis of CD40L-treated monocytes. Oxaprozin pro-apoptotic activity was associated with the inhibition of CD40L-triggered Akt and NF-kappaB phosphorylation and the activation of caspase 3. In conclusion, our data suggest that oxaprozin-induced apoptosis in CD40L-treated human monocytes is associated with previously unknown cyclooxygenase (COX)-independent pathways. These intracellular proteins might be promising pharmacological targets to increase apoptosis in CD40L-treated monocytes.
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PMID:Oxaprozin-induced apoptosis on CD40 ligand-treated human primary monocytes is associated with the modulation of defined intracellular pathways. 1967 23

Cholesterol secoaldehyde (3beta-hydroxy-5-oxo-5,6-secocholestan-6-al or ChSeco) is an oxysterol known to be formed in reactions of ozone with cholesterol and also when cholesterol-5alpha-hydroperoxide undergoes Hock cleavage. In view of its widespread occurrence and atherogenic potential, we examined the effects of ChSeco on mouse J774 macrophage viability and events associated with apoptosis. A dose-dependent decrease in cell viability, disruptions in mitochondrial transmembrane potential (64+/-5.5%; mean+/-SD, n=3), increased levels of cytosolic cytochrome c (8.8+/-0.84 ng/ml; mean+/-SD, n=3), activation of caspase-3 (ca. 3.6-fold) and caspase-9 (ca.1.8-fold), and increased DNA fragmentation (ca. 5-fold), all indicative of apoptosis, were observed in response to exposure to ChSeco. The apoptotic nature of cell death in macrophages was confirmed by dual staining with acridine orange and ethidium bromide. However, unlike the case with cardiomyoblasts and neuronal cells, the apoptotic process in these immune cells was not mediated by increased levels of reactive oxygen species as indicated by a minimal or no increase in 2',7'-dichlorofluorescein fluorescence. It is suggested that the apoptotic process is mediated via the mitochondrial pathway and that ChSeco formed in biological environments contributes to the initiation, progression, and culmination of atherosclerotic plaque formation, as these processes are critically dependent on macrophage apoptosis.
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PMID:Cholesterol secoaldehyde induces apoptosis in J774 macrophages via mitochondrial pathway but not involving reactive oxygen species as mediators. 1973 50

In the course of screening for substances that inhibit etoposide (10 microg/ml)-induced apoptosis in human leukemia U937 cells, fungal strain F000120, which exhibits potent inhibitory activity, was selected. The active compound was purified from an ethyl acetate extract of the microorganism by Sep-pak C18 column chromatography and HPLC, and was identified as heptelidic acid (koningic acid) by spectroscopic methods. This compound inhibited caspase- 3 induction in U937 cells with an IC(50) value of 40 microM after 8 h of etoposide treatment. Fluorescent dye staining with acridine orange and ethidium bromide showed that heptelidic acid inhibited apoptosis. Furthermore, it was found that DNA fragmentation and caspase-3 activation, the biological hallmarks of apoptosis, were inhibited by the compound in a dose-dependent manner, suggesting that heptelidic acid inhibits etoposide-induced apoptosis via downregulation of caspases.
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PMID:Heptelidic acid, a sesquiterpene lactone, inhibits Etoposide-induced apoptosis in human leukemia U937 cells. 1973 16

Mercury is a well-known highly toxic metal. In this study, we characterize and investigate the cytotoxicity and its possible mechanisms of inorganic mercury in pancreatic beta-cells. Mercury chloride (HgCl2) dose-dependently decreased the function of insulin secretion and cell viability in pancreatic beta-cell-derived HIT-T15 cells and isolated mouse pancreatic islets. HgCl2 significantly increased ROS formation in HIT-T15 cells. Antioxidant N-acetylcysteine effectively reversed HgCl2-induced insulin secretion dysfunction in HIT-T15 cells and isolated mouse pancreatic islets. Moreover, HgCl2 increased sub-G1 hypodiploids and annexin-V binding in HIT-T15 cells, indicating that HgCl2 possessed ability in apoptosis induction. HgCl2 also displayed several features of mitochondria-dependent apoptotic signals including disruption of the mitochondrial membrane potential, increase of mitochondrial cytochrome c release and activations of poly (ADP-ribose) polymerase (PARP) and caspase 3. Exposure of HIT-T15 cells to HgCl2 could significantly increase both apoptotic and necrotic cell populations by acridine orange/ethidium bromide dual staining. Meanwhile, HgCl2 could also trigger the depletion of intracellular ATP levels and increase the LDH release from HIT-T15 cells. These HgCl2-induced cell death-related signals could be significantly reversed by N-acetylcysteine. The intracellular mercury levels were markedly elevated in HgCl2-treated HIT-T15 cells. Taken together, these results suggest that HgCl2-induced oxidative stress causes pancreatic beta-cell dysfunction and cytotoxicity involved the co-existence of apoptotic and necrotic cell death.
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PMID:Inorganic mercury causes pancreatic beta-cell death via the oxidative stress-induced apoptotic and necrotic pathways. 2000 36


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