BACKGROUND: Histone deacetylase inhibitors (HDACIs) have been reported to induce apoptosis in cancer cells. The effects of trichostatin A (TSA) on gastric cancer cells have not been well characterized. This study was aimed to explore the effects and mechanisms of TSA on human gastric cancer SGC-7901 cells. METHODS: The cells ...

Caffeic acid phenyl ester (CAPE), a biologically active ingredient of propolis, has several interesting biological properties including antioxidant, anti-inflammatory, antiviral, immunostimulatory, anti-angiogenic, anti-invasive, anti-metastatic and carcinostatic activities. Recently, several groups have reported that CAPE is cytotoxic to tumor cells but not to normal cells. In this study, we investigated the ...

Apoptotic signals are typically accompanied by activation of aspartate-specific cysteine proteases called caspases, and caspase-3 and -7 play crucial roles in the execution of apoptosis. Previously, using the proteomic approach, protein disulfide isomerase (PDI) was found to be a candidate substrate of caspase-7. This abundant 55 kDa protein introduces disulfide ...

Protease-activated receptors (PARs) belong to a family of G protein-coupled receptors activated by serine proteases via proteolytic cleavage. PARs are expressed on epithelial cells, endothelial cells, and leukocytes, indicating a role in controlling barrier function against external danger. During inflammation, microorganisms as well as host immune cells release various proteases ...

The potential role of cysteine cathepsins, especially cathepsin B, in Fas/CD95-induced apoptosis was investigated using wild-type and cathepsin B-deficient primary skin fibroblasts. Apoptosis was induced with an anti-Fas/CD95 antibody in the presence of cycloheximide and no difference was observed between the two genotypes. First cells with damaged mitochondria were observed ...

The nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1), which was initially known to be highly activated by oxidative stress-induced DNA strand breaks, has been shown to be involved in the pathophysiology of acute and chronic inflammatory diseases. PARP-1 deficiency in mice led to the discovery of its coactivating function in the nuclear ...

Our quest to understand the complex inner workings of the cell depends on the development of new technologies that allow the study of global regulatory events as they happen within their native cellular environment. Post-translational processing of proteins by proteases is one such regulatory process that can control many aspects ...

Prostate apoptosis response-4 (Par-4) is a proapoptotic gene that selectively induces cell death in most cancer cells. In addition to the increased percentage of apoptotic cells, caspase-3 activity, and poly (ADP-ribose) polymerase (PARP) cleavage, we demonstrate that elevated expression of Par-4 and nuclear entry resulted in apoptosis of nasopharyngeal carcinoma ...

Melittin (MEL), a major polypeptide in bee venom (BV), is known to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in MEL-induced apoptosis have not been fully elucidated, especially in human leukemic cells. In the present study, we report that MEL induces apoptosis in leukemic ...

Response to genotoxic stress may trigger the activation of distinct mechanisms that serve to promote cell death, including apoptosis and necrosis. In this study we examined the response of human fibroblasts, either proficient or deficient for the damage-activated protein kinase ataxia telangiectasia-mutated (ATM), to the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Analysis ...

Bioassay-guided phytochemical study of Androsace umbellata led to the successful isolation of saxifragifolin B (SB) for the first time. The anti-tumor effect of SB was firstly reported that it was shown to have potent cytotoxicity on human hepatoma HepG2 cells with IC50 value of 11.9 microM at 24 h. Mechanistic ...

Giardia intestinalis is a flagellated protozoan which causes enteric disease worldwide. Giardia trophozoites infect epithelial cells of the proximal small intestine and can cause acute or chronic diarrhea. The mechanism of epithelial injury in giardiasis remains unknown. A number of enteric pathogens, including protozoan parasites, are able to induce enterocyte ...

Agaricus blazei is a medicinal mushroom that possesses antimetastatic, antitumor, antimutagenic, and immunostimulating effects. However, the molecular mechanisms involved in A. blazei-mediated apoptosis remain unclear. In the present study, to elucidate the role of the Bcl-2 in A. blazei-mediated apoptosis, U937 cells were transfected with either empty vector (U937/vec) or ...

The aim of the present study was to research the apoptosis of human hepatocellular carcinoma cell line HepG 2 induced by pitavastatin. HepG 2 cells were treated with increasing doses of pitavastatin or with mevalonic acid for 48 h. The proliferation of cells was detected with WST-8. The morphology of ...

Clostridium difficile toxin A (TcdA) is one of two homologous glucosyltransferases that mono-glucosylate Rho GTPases. HT29 cells were challenged with wild-type and mutant TcdA to investigate the mechanism by which apoptosis is induced. The TcdA-induced re-organization of the actin cytoskeleton led to an increased number of cells within the G2/M ...

The first calpain protease was discovered over 40 years ago now, yet despite the vast amount of literature that has subsequently emerged detailing their involvement in the pathophysiology of a variety of human diseases, it is only in the last decade that calpain-mediated actions along the secretory pathway have begun ...

We found previously that organophosphorus pesticides (OPs) significantly inhibited natural killer (NK) activity. To explore the mechanism of OP-induced inhibition of NK activity, we investigated whether OPs can induce apoptosis in NK cells in the present study. We used NK-92CI and NK-92MI cells, which are interleukin-2 independent human NK cell ...

Coxiella burnetii, the cause of human Q fever, is an aerosol-borne, obligate intracellular bacterium that targets host alveolar mononuclear phagocytic cells during infection. In all cell types examined, C. burnetii establishes a replicative niche in a lysosome-like parasitophorous vacuole where it carries out a lengthy infectious cycle with minimal cytopathic ...

Geminin is an important cell cycle regulator having a dual role in cell proliferation and differentiation. During proliferation, Geminin controls DNA synthesis by interacting with the licensing factor Cdt1 and interferes with the onset of differentiation by inhibiting the activity of transcription factors such as Hox and Six3. During early ...

Caspase-3 has classically been defined as the main executioner of programmed cell death. However, recent data supports the participation of this protease in non-apoptotic cellular events including cell proliferation, cell cycle regulation, and cellular differentiation. In this study, astroglial cleavage of caspase-3 was analyzed following excitotoxic damage in postnatal rats ...

Beta-sitosterol is the main dietary phytosterol found in plants and has been shown to inhibit proliferation and induce apoptosis in human solid tumors such as colon and breast cancers. However, the mechanism by which beta-sitosterol induces apoptosis is not completely understood in leukemic cells. This study investigated the mechanism of ...

Caspase-3 is an essential executioner of apoptosis responsible for regulating many important cellular processes, among them the number of circulating monocytes, central players in the innate immune response. The activation of caspase-3 requires its processing from an inactive precursor. Here we show that the small heat shock protein 27 (Hsp27) ...

Anthracenedione derivatives are potent cytotoxic agents to tumor cells. In this study, we investigated the anticancer activities of anthracenedione derivative 1403P-3 separated from the secondary metabolites of the mangrove endophytic fungus No. 1403. Our results demonstrated that 1403P-3 showed potent cytotoxicity not only to human epidermoid carcinoma drug-sensitive parental KB ...

Apoptosis is the major mechanism by which eukaryotic organisms eliminate potentially dangerous, superfluous and damaged cells. Initially, nuclei and mitochondria were found to be the key organelles involved in the process. However, recent data suggest that lysosomes and the endoplasmic reticulum also play important roles in the process. A number ...

Unregulated apoptosis can be due to a disruption in the balance and control of both intra- and inter-cellular proteolytic activities leading to various disease states. Many proteases involved in apoptotic processes are yet to be identified; however, several are already well characterized. Caspases traditionally held the predominant role as prime ...

A series of new pyrazole derivatives from emodin synthesized in our lab have been shown to have much stronger cytotoxicity than emodin against various tumor cell lines. This study was to examine the apoptosis-inducing activity of these new emodin derivatives in human hepatocellular carcinoma HepG2 cell culture for a better ...

The apoptosis of lens epithelial cells has been proposed as the common basis of cataract formation, with oxidative stress as the major cause. This study was performed to investigate the protective effect of the herbal constituent parthenolide against oxidative stress-induced apoptosis of human lens epithelial (HLE) cells and the possible ...

DC-81, an antitumor antibiotic produced by the Streptomyces species, belongs to pyrrolo[2,1-c] [1,4]benzodiazepine (PBD), which are potent inhibitors of nucleic acid synthesis. We previously reported an efficient synthesis of PBD hybrids linked with indole carboxylates. This is the first demonstration on the mechanism of the anticancer effect of PBD hybrid ...

Proteases were, for a long time, mainly considered as protein degrading enzymes. However, in the last decade this view has changed dramatically, and the focus is now on proteases as signalling molecules. One of the best examples is apoptosis, the major mechanism used by eukaryotes to remove superfluous, damaged and ...

Apoptosis is an essential physiological process in embryonic development. In the developing eye of vertebrates, three periods of developmental apoptosis can be distinguished: early, intermediate and later. Within the apoptosis pathway, caspases play a crucial role. It has also been shown that HSP110 may have a potential role in apoptosis. ...

Nanoparticle realgar powders (NRP) inhibited U937 cell growth in a time and dose-dependent manner. U937 cells treated with NRP showed typical characteristics of apoptosis including the morphological changes and DNA fragmentation. Caspase family inhibitor (z-VAD-fmk), caspase-8, -9 inhibitor (z-IETD-fmk, Ac-LEHD-CHO, respectively) and caspase-3 inhibitor (z-DEVD-fmk) partially prevented NRP -induced apoptosis. ...

Although the cardioprotection afforded by the late phase of ischemic preconditioning (PC) in ischemia/reperfusion (I/R) injury has been well studied, it is unknown whether this beneficial effect can be attributed to inhibition of apoptosis. We hypothesized that ischemic PC affords protection by suppressing apoptosis and examined the underlying mechanisms. Myocardial ...

In this study, we show that adenosine monophosphate-activated protein kinase (AMPK) is expressed and activated in multiple myeloma cells. The inhibition of AMPK induced growth arrest and reduction of cell viability in the cell viability assay using the water-soluble tetrazolium salt 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1 assay). Induction of apoptosis was determined ...

Calcium ion is essential for cellular functions including signal transduction. Uncontrolled calcium stress has been linked causally to a variety of neurodegenerative diseases. Thapsigargin, which inhibits Ca(2+)-ATPase in the endoplasmic reticulum (ER) and blocks the sequestration of calcium by the ER, induced apoptotic cell death (chromatin condensation and nuclear fragmentation) ...

AIM: Intravascular brachytherapy efficiently reduces vascular smooth muscle cell (SMC) proliferation, interstitial matrix production, vascular remodeling and restenosis rate after revascularization injury of coronary arteries. In this study we examined the molecular mechanisms of the cytotoxic effect of Re-188-mediated beta-irradiation on a SMC culture model compared to that of paclitaxel. ...

The effects of ginseng extracts (GE) and several ginsenosides on cytokine-induced apoptosis were evaluated. In pancreatic beta-cell line MIN6N8 cells, the inhibitory effect of GE was significantly observed at 25-100 microg/mL: an 86-100% decrease of cytoplasmic DNA fragments quantified by an ELISA. The inhibitory effect of red ginseng (RG) extract ...

This study shows that cilostazol displayed a potent inhibition of PARP with IC(50) of 883+/-41 nM in the enzyme assay, and also significantly reversed H(2)O(2)-evoked elevated PARP activity and reduced NAD(+) levels in the PC12 cells with improvement of cell viability. In in vivo study, inhibition of PARP activity by ...

Norcantharidin (NCTD) is known to have anti-cancer potentials. The aim of this study was to assess the apoptosis-inducing effect of NCTD on human leukemic Jurkat cells. We found that NCTD preferentially inhibited the growth of Jurkat cells in a dose- and time-dependent manner, but not the growth of normal blood ...

Serine proteases such as thrombin, mast cell tryptase, trypsin, or cathepsin G, for example, are highly active mediators with diverse biological activities. So far, proteases have been considered to act primarily as degradative enzymes in the extracellular space. However, their biological actions in tissues and cells suggest important roles as ...

The administration of methimazole is known to induce cell death in rat olfactory receptor neurons (ORNs). We investigated whether this injury occurs via apoptosis or through necrosis and whether it involves the extrinsic or intrinsic pathway. Rats were intraperitoneally injected with vehicle (control) or 300 mg/kg methimazole. The experimental animals ...

Hypersecretion of cytokines and serine proteases has been observed in asthma. However, the influence of proteases and protease-activated receptors (PARs) on monocyte chemoattractant protein-1 (MCP-1) release from airway epithelial cells remains largely unknown. In the present study, A549 cells were challenged with agonists of PARs, and levels of MCP-1 released ...

Sulindac sulfone (also known as exisulind) and its chemical derivatives are promising anticancer agents capable of inducing apoptosis in a variety of malignant cell types with minimal toxicity to normal cells. Here, we tested the ability of alpha-tocopheryl succinate (TOS), another promising anticancer agent, to sensitize colon cancer cells to ...

Cathepsin D (CTSD, EC 3.4.23.5) is well known aspartyl protease. Among different role in cell physiology, a new function of this enzyme is examined. Cathepsin D is an important regulator of apoptotic pathways in cells. It acts at different stage of intrinsic and extrinsic pathway of apoptosis. Cathepsin D can ...

Genistein (G), an isoflavone, and guggulsterone (GS), the active substance in guggulipid, have been reported to possess therapeutic effects for obesity. In the present study, we investigated the effects of combinations of G plus GS on apoptosis and adipogenesis in 3T3-L1 cells. In mature adipocytes, G and GS individually caused ...

To investigate the apoptosis effect of SARS coronavirus nucleocapsid protein on cultured cell lines and to explore the possible pathway of apoptosis. pCDNA3.1(-)/his-myc vector containing the SARS coronavirus nucleocapsid gene (N), matric gene (M), spike gene (S) were transfected into COS-1, Huh-7 and HepG2 cells. Apoptosis induced by SARS coronavirus ...

BACKGROUND: West Nile virus (WNV) infection can cause severe meningitis and encephalitis in humans. Apoptosis was recently shown to contribute to the pathogenesis of WNV encephalitis. Here, we used WNV-infected glioma cells to study WNV-replication and WNV-induced apoptosis in human brain-derived cells. RESULTS: T98G cells are highly permissive for lytic ...

In a preliminary study, we found that benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD- fmk), unlike Boc-aspartyl(OMe)-fluoromethylketone (BocD-fmk), at usual dosage could not prevent genistein-induced apoptosis of p815 mastocytoma cells. This study was undertaken to reveal the mechanism underlying the incapability of zVAD-fmk in preventing this type of apoptosis. We observed that 14-3-3 protein level ...

Trichostatin A (TSA), originally developed as an antifungal agent, is one of potent histone deacetylase (HDAC) inhibitors, which are known to cause growth arrest and apoptosis induction of transformed cells, including urinary bladder, breast, prostate, ovary, and colon cancers. However, the effect of HDAC inhibitors on human non-small cell lung ...

The chemical warfare agent sulfur mustard (SM) is a strong alkylating agent that leads to erythema and ulceration of the human skin several hours after exposure. Although SM has been intensively investigated, the cellular mechanisms leading to cell damage remain unclear. Apoptosis, necrosis and direct cell damage are discussed. In ...

Syringolin A is a new plant elicitor produced by the plant pathogen Pseudomonas syringae pv. syringae. The goal of this study was to investigate whether syringolin A exhibits anti-proliferative properties in cancer cells. The treatment of human neuroblastoma (NB) cells (SK-N-SH and LAN-1) and human ovarian cancer cells (SKOV3) with ...