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)

This study evaluated the biologic activity of epicatechin gallate (ECG), a polyphenol in tea, to carcinoma HSC-2 cells and normal HGF-2 fibroblasts cells from the human oral cavity. The relative cytotoxicity of ECG, as compared to five other polyphenols in tea, was evaluated. For the HSC-2 carcinoma cells, ECG, catechin gallate (CG), and epigallocatechin gallate (EGCG) grouped as highly toxic, epigallocatechin (EGC) as moderately toxic, and catechin (C) and epicatechin (EC) as least toxic. For the HGF-2 fibroblasts, ECG and CG grouped as highly toxic, EGCG as moderately toxic, and EGC, C, and EC as least toxic. The cytotoxic effects of the polyphenols were more pronounced to the carcinoma, than to the normal, cells. The addition of ECG to cell culture medium led to the generation of hydrogen peroxide (H2O2). However, ECG, as compared to EGCG, was a poor generator of H2O2 and, hence, the cytotoxicity of ECG was unaffected by the presence of the antioxidants, N-acetyl cysteine and glutathione, and catalase. The cytotoxicity of ECG was unaffected by a metabolic activating system, i.e., a hepatic microsomal S-9 mix. DNA fragmentation, caspase-3 activity, and nuclear staining, both with acridine orange and the TUNEL procedure, were used to assess ECG-induced apoptosis. ECG induced apoptosis in the carcinoma HSC-2 cells, but not in the normal HGF-2 fibroblasts. This research supports those studies suggesting that tea green is an effective chemopreventive agent of oral carcinoma.
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PMID:Differential in vitro cytotoxicity of (-)-epicatechin gallate (ECG) to cancer and normal cells from the human oral cavity. 1564 37

The cholesterol-lowering medications, statins, inhibit cellular proliferation and induce apoptosis in an array of cancer cell lines, including melanoma. We investigated the apoptotic mechanism of lovastatin on human melanoma cell lines in vitro. The cytotoxicity of statins on multiple cell lines was examined by Cell Titer 96 Aqueous One solution cell proliferation assay (MTS assay). Apoptosis was assayed by ethidium bromide and acridine orange morphologic assays, an Annexin V apoptosis detection kit and active caspase 3 assays. Farnesyl pyrophosphate and geranylgeranyl pyrophosphate add-back experiments were performed to better define the molecular mechanisms mediating lovastatin cytotoxicity. Lovastatin caused cytotoxicity in human and murine melanoma cells, but did not induce toxicity in an epidermoid carcinoma cell line A431. For human melanoma cells, lovastatin precipitated cell rounding, increased the percentage of apoptotic cells detected by ethidium bromide and acridine orange staining and by the Annexin V apoptosis detection kit, and resulted in a 50-fold increase in active caspase 3, corroborating that lovastatin induced apoptosis. Adding back geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate, reversed the effects of lovastatin in A375 cells. Of the five statins tested, pravastatin was least effective in killing melanoma cells. Lovastatin induced caspase-dependent apoptosis in multiple melanoma cell lines via a geranylation-specific mechanism. This study supports a possible role of lovastatin as a therapeutic, adjuvant or chemopreventive agent for melanoma.
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PMID:Lovastatin-induced apoptosis in human melanoma cell lines. 1584 40

This study was aimed to investigate the effects of human bone marrow fibroblastoid stromal cell line (HFCL) on chemosensitivity of acute myeloid leukemia sensitive HL-60 cell line and multidrug-resistant (MDR) HL-60/VCR cell line in vitro co-culture. Setting up co-culture system of HL-60 or HL-60/VCR cells in direct contact with HFCL cells, or with HFCL cells separated by transwell, and exposing HL-60 or HL-60/VCR cells to different concentrations of topotecon (TPT), morphologic evidence for apoptosis was determined by staining with Wright-Giemsa stain and acridine orange/ethidium bromide (AO/EB). Cell cycle, sub-G(1) and annexin V FITC staining were detected by flow cytometry. The expression of active caspase-3, Bcl-2 and Pgp was detected by Western blot. The results showed that HL-60 or HL-60/VCR cells treated by TPT revealed characteristic apoptotic morphological changes by Wright-Giemsa and AO/EB staining. The percentage of annexin V-positive cells and apoptotic cells decreased when they were cocultured with HFCL cells. The proportion of G(0)/G(1) HL-60 or HL-60/VCR cells treated by TPT increased and the sub-G(1) appeared significantly, but apoptotic and sub-G cells reduced after direct contact with HFCL cells. Meanwhile, although HL-60 or HL-60/VCR cells treated by TPT expressed activated caspase-3, and the expression of Bcl-2 decreased, the expression of activated caspase-3 decreased and Bcl-2 increased after direct contact with HFCL cells. In conclusion, HFCL stromal cells can prevent TPT-induced apoptosis in HL-60 and HL-60/VCR cells via modulation of Bcl-2 and active caspase-3.
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PMID:[Effect of bone marrow stromal cells on the apoptotic sensitivity of HL-60 and HL-60/VCR cells]. 1585 94

Icariin is a flavonoid isolated from Epimedium and is considered to be the major pharmacological active component of Epimedii Herba. In the present investigation, we studied and confirmed the protective activity of icariin on H2O2-induced injury in human umbilical vein endothelial cell line: ECV-304. Eighteen-hour treatment with 750 micromol l(-1) H2O2 significantly decreased the viability of ECV-304 cells, which was accompanied with apparent apoptotic features, including distinct cell morphological alteration and the increase of caspase-3 expression. In addition, it is observed that H2O2 increased the amounts of malondialdenhyde (MDA) and the dehydrogenase (LDH), and decreased the content of nitric oxide (NO) in ECV-304 cells. However, pretreatment with 0.1-50 micromol l(-1) icariin resulted in a significant recovery from H2O2-induced cell apoptosis. Also, it decreased other H2O2-induced damage in a concentration-dependent manner. Furthermore, pretreatment with icariin decreased the expression of caspase-3, which was known to be involved as a key role executor in H2O2-induced cell apoptosis. The endothelial cells apoptosis were detected by acridine orange/ethidium bromide (AO/EB) dual staining as well as flow cytometry, and the expression of pro-apoptotic factor caspase-3 were detected by immunocytochemical method. Taken together, these data suggest that protective effects of icariin against oxidative injuries of ECV-304 cells may be achieved via decreasing of caspase expression.
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PMID:Protective effects of icariin on human umbilical vein endothelial cell injury induced by H2O2 in vitro. 1596 84

Gentamicin accumulates in lysosomes and induces apoptosis in kidney proximal tubules and renal cell lines. Using LLC-PK1 cells, we have examined the concentration- and time-dependency of the effects exerted by gentamicin (1-3 mM; 0-3 days) on (i) lysosomal stability; (ii) activation of mitochondrial pathway; (iii) occurrence of apoptosis (concentrations larger than 3 mM caused extensive necrosis as assessed by the measurement of lactate dehydrogenase release). Within 2 h, gentamicin induced a partial relocalization [from lysosomes to cytosol] of the weak organic base acridine orange. We thereafter observed (a) a loss of mitochondrial membrane potential (as from 10 h, based on spectrophotometric and confocal microscopy using JC1 probe) and (b) the release of cytochrome c from granules to cytosol, and the activation of caspase-9 (as from 12 h; evidenced by Western blot analysis). Increase in caspase-3 activity (assayed with Ac-DEVD-AFC in the presence of z-VAD-fmk]) and appearance of fragmented nuclei (DAPI staining) was then detected as from 16 to 24 h together with nuclear fragmentation. Gentamicin produces a fast (within 4 h) release of calcein from negatively-charged liposomes at pH 5.4, which was slowed down by raising the pH to 7.4, or when phosphatidylinositol was replaced by cardiolipin (to mimic the inner mitochondrial membrane). The present data provide temporal evidence that gentamicin causes apoptosis in LLC-PK1 with successive alteration of the permeability of lysosomes, triggering of the mitochondrial pathway, and activation of caspase-3.
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PMID:Gentamicin-induced apoptosis in LLC-PK1 cells: involvement of lysosomes and mitochondria. 1603 43

The effects of a novel kind of nitrogen heterocycle compound, which was synthesized in our laboratory previously, on human chronic myelogenous leukemia K562 cells were investigated. The morphological changes were observed by Acridine orange (AO) staining. The screened results through DNA fragmentation and the Annexin V-FITC/PI staining assay showed that compound 8 blocked cell cycles at G(1) phase which led to apoptosis. The increase of caspase-3, 8, and 9 was detected, indicating that both of death-receptor and mitochondria-pathways were activated. Compound 8 induced a biphasic alteration in mitochondrial membrane potential of K562 cells. A dramatic elevation of Ca(2+) was also observed. In addition, a transient increase of ROS was also involved in the process. This study showed that compound 8 might be a potential chemopreventive agent for chronic myelogenous leukemia. It would guide our future work to synthesize more compounds derived from compound 8, which might have better effect, and to determine the target protein. Moreover, it might also provide a background mechanism for the introduction of this new type of promising therapeutic agent.
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PMID:A novel kind of nitrogen heterocycle compound induces apoptosis of human chronic myelogenous leukemia K562 cells. 1646 24

Our aim was to prepare curcumin derivatives and study their apoptosis-inducing effects on bladder cancer cells in order to establish a basis for targeted chemotherapy of cancer. n-Maleoyl-L-valine-curcumin (NVC) and n-maleoyl-glycine-curcumin (NGC) were chemically synthesized. Intracellular esterase activity of the human bladder cancer EJ cell line and renal tubular epithelial (HKC) cells was examined by 6-carboxyfluorescein diacetate fluorometry. After incubation with NVC or NGC for 6-24 h, cell viability was detected by MTT colorimetry. Cell apoptosis and apoptotic rates were measured by acridine orange/ethidium bromide staining, TUNEL labeling and flow cytometry. Intracellular caspase-3 activities were determined by spectrophotometry. The esterase activity within EJ cells was 10.2-fold higher than that of HKC cells, which was abolished by bis-p-nitrophenylphosphate, an esterase inhibitor, resulting in decreases in NVC- and NGC-mediated cell viability arrest. For EJ cells, the IC50 values of NVC (20.1 micromol/l) and NGC (18.7 micromol/l) were close to curcumin (16.5 micromol/l). Meanwhile, their IC50 values on HKC cells were, respectively, 4.06- and 3.23-fold higher than curcumin. Moreover, NVC and NGC induced apoptosis of EJ cells by 10.13-23.36 and 12.42-28.56%, respectively. Administration of these two derivatives resulted in decreased apoptosis of HKC cells compared with curcumin. The caspase-3 activities of EJ cells, but not of HKC cells, were 5.21- and 5.63-fold enhanced by NVC and NGC, respectively. Thus, novel esterase-sensitive curcumin derivatives were synthesized, which induced extensive apoptosis of bladder cancer EJ cells, but not normal cells.
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PMID:Apoptosis-inducing effects of curcumin derivatives in human bladder cancer cells. 1652 Jun 56

Although the apoptosis of chondrocytes plays an important role in endochondral ossification, its mechanism has not been elucidated. In this study, we show that guanosine induces chondrocyte apoptosis based on the results of acridine orange/ethidium bromide staining, caspase-3 activation, and sub-G1 fraction analysis. The potent inhibitory effect of dipyridamole, a nucleoside transporter blocker, indicates that extracellular guanosine must enter the chondrocytes to induce apoptosis. We found that guanosine promotes Fas-Fas ligand interaction which, in turn, leads to chondrocyte apoptosis. These findings indicate a novel mechanism for endochondral ossification via metabolic regulation.
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PMID:Metabolic loading of guanosine induces chondrocyte apoptosis via the Fas pathway. 1695 19

Twenty trihaloacetylazulene derivatives with one atom of fluorine, chlorine, bromine or iodine was investigated for their tumor-specific cytotoxicity and apoptosis-inducing activity against three human normal cells (gingival fibroblast, HGF; pulp cell, HPC; periodontal ligament fibroblast, HPLF) and four human tumor cell lines (squamous cell carcinoma, HSC-2, HSC-3, HSC-4; promyelocytic leukemia, HL-60). There was no apparent difference in the cytotoxic activity between 2-methoxyazulenes [1a-1e, 2a-2e] and 2-ethoxyazulenes [3a-3e, 4a-4e]. Trichloroacetylazulenes [2a-2e, 4a-4e] generally showed higher cytotoxicity and tumor-specificity (expressed as a TS value) as compared with the corresponding trifluoroacetylazulenes [1a-1e, 3a-3e]. Substitution of chloride [1c, 2c, 3c. 4c], bromide [1d, 2d, 3d, 4d] or iodine [1e, 2e, 3e, 4e] at the C-3 position further enhanced cytotoxic activity against four tumor cell lines, especially HL-60 cells. Among twenty trihaloacetylazulene derivatives, two compounds [2d] and [4c] showed the highest tumor specificity (TS = > 3.5 and > 2.5, respectively). Compounds [2d] and [4c] induced apoptotic cell death characterized by caspase-3, -8 and -9 activation and internucleosomal DNA fragmentation in HL-60 cells. On the other hand, compounds [2d] and [4c] induced autophagic cell death characterized by lower activation of caspases, lack of DNA fragmentation, vacuolization and autophagosome formation detected by acridine orange and LC3-GFP fluorescence, without the decline of the intracellular concentration of three major polyamines in HSC-4 cells. The cytotoxic activity of [4c], but not [2d], was slightly reduced by 3-methyladenine, an inhibitor of autophagy. These results suggest the diversity of cell death type induced in human tumor cell lines by trihaloacetylazulene derivatives.
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PMID:Tumor-specificity and type of cell death induced by trihaloacetylazulenes in human tumor cell lines. 1735 25

D-beta-hydroxybutyrate (DbetaHB) is a predominant member of ketone bodies produced by hepatocytes and, to a lesser extent, by astrocytes. It is an alternative source of energy in the brain when glucose supply is depleted such as during starvation. It has been reported that ketone bodies could protect dopaminergic culture. However, the biological function of DbetaHB in Parkinson disease (PD) is still unclear. In the present work, we investigated the role of DbetaHB in protecting rat pheochromocytoma (PC12) cells from apoptosis induced by 6-Hydroxydopamine (6-OHDA). DbetaHB rescued PC12 cells from apoptotic death induced by 6-OHDA by MTT assay, acridine orange (AO) staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and the activity of caspase-3. DbetaHB prevented the decrease of cell viability and the increase of caspase-3 activity induced by 6-OHDA in a dose-dependent manner in PC12 cells. AO and TUNEL staining showed that DbetaHB prevented the apoptosis of PC12 cells induced by 6-OHDA. The ratio of Bcl-2/Bax at mRNA levels, which regulates the apoptosis of PC12 cells when exposed to 6-OHDA, increased when DbetaHB was preincubated. The data showed that DbetaHB inhibited the apoptosis of PC12 cells induced by 6-OHDA in relation to up-regulating the ratio of Bcl-2/Bax mRNA.
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PMID:D-beta-hydroxybutyrate inhibits the apoptosis of PC12 cells induced by 6-OHDA in relation to up-regulating the ratio of Bcl-2/Bax mRNA. 1736 4


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