OBJECTIVES: The incompletely ripened fruit of Rubus coreanum (IRFRC) has been used in traditional herbal medicine to manage various diseases. To explore the possibility that IRFRC has chemopreventive effects, we examined whether or not extracts of IRFRC inhibits HT-29 cell growth and explored the mechanism for this effect. METHODS: We ...

Caspase-3, an apoptotic executor, has been shown in recent years to mediate non-lethal events like cellular proliferation and differentiation, primarily in studies related to non-neural tissue. In central nervous system development, the role of active caspase-3 is still unclear. We provide the first evidence for a potential new role of ...

PURPOSE: The primary purpose of this study was to characterize photoreceptor apoptosis in the rd mouse. Given that apoptosis is the final common pathway in many cases of retinal degeneration, the ability to retard or even arrest this process may ameliorate retinal disorders such as retinitis pigmentosa (RP). The absence ...

Bak Foong Pills (BFP), a traditional Chinese medicine used for centuries for the enhancement of women's health, was shown to display neuro-protective activity in the 1-methyl-4-phenyl-1,2,4,6,-tetrahydro-pyridine (MPTP)-induced mouse model in a previous study. In order to elucidate its mechanism of action, we investigated the anti-apoptotic properties of Bak Foong Pills ...

The activation of caspases is a central step in apoptosis and may also be critical for terminal differentiation of epidermal keratinocytes (KC). In particular, caspase-3 has been implicated in the differentiation of embryonic KC as well as in programmed cell death of KC, and caspase-14 has been suggested to function ...

Decreases in the intracellular concentrations of both K(+) and Cl(-) have been implicated in playing a major role in the progression of apoptosis, but little is known about the temporal relationship between decreases in electrolyte concentration and the key events in apoptosis, and there is no information about how such ...

Hyperoxia induces extensive DNA damage and lung cell death by apoptotic and nonapoptotic pathways. We analyzed the regulation of Poly(ADP-ribose)polymerase-1 (PARP-1), a nuclear enzyme activated by DNA damage, and its relation to cell death during hyperoxia in vitro and in vivo. In lung epithelial-derived A549 cells, which are known to ...

We previously reported that the garlic-derived compound S-allylmercaptocysteine (SAMC) causes growth inhibition, mitotic arrest, and induction of apoptosis in SW480 human colon cancer cells by inducing microtubule depolymerization and c-Jun NH(2) terminus kinase-1 activation. In the present study, we compared the aforementioned effects of SAMC to those of a series ...

The ability of the intracellular bacterium Legionella pneumophila to cause disease is totally dependent on its ability to modulate the biogenesis of its phagosome and to replicate within alveolar cells. Upon invasion, L. pneumophila activates caspase-3 in macrophages, monocytes, and alveolar epithelial cells in a Dot/Icm-dependent manner that is independent ...

Xanthohumol (XN) is one of the major prenylflavonoids found in hop cones (Humulus lupulus L.). In this study, we investigated the cell growth inhibitory potential of XN on cultured human colon cancer cells. Cell proliferation was measured by sulforhodamine B staining. Poly(ADP-ribose)polymerase (PARP) cleavage, activation of caspases-3, -7, -8, and ...

Proteases function at every level in host defense, from regulating vascular hemostasis and inflammation to mobilizing the "rapid responder" leukocytes of the immune system by regulating the activities of various chemoattractants. Recent studies implicate proteolysis in the activation of a ubiquitous plasma chemoattractant, chemerin, a ligand for the G-protein-coupled receptor ...

The cytoskeleton is critical to neuronal functioning and survival. Cytoskeletal alterations are involved in several neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. We studied the possible pathways involved in colchicine-induced apoptosis in cerebellar granule neurons (CGNs). Although colchicine evoked an increase in caspase-3, caspase-6 and caspase-9 activation, selective caspase ...

Although histone deacetylase (HDAC) inhibitors are emerging as a promising new treatment strategy in malignancy, how they exert their effect on human non-small cell lung cancer cells is as yet unclear. This study was undertaken to investigate the underlying mechanism of an HDAC inhibitor, Trichostatin A (TSA), -induced apoptosis in ...

Interleukin-1beta (IL-1beta) is a pivotal proinflammatory cytokine. To investigate the mechanism of IL-1beta-induced cell death in human malignant melanoma A375-S2 cells, MTT assay, photomicroscopical observation, DNA agarose gel electrophoresis, radioimmunoassay and Western blot analysis were carried out. IL-1beta did not only induce nuclear condensation and DNA fragmentation, but also increased ...

We have found in the previous study that 6-methoxydihydrosanguinarine (6ME), a benzophenanthridine alkaloid isolated from Hylomecon species, may have potential as a chemotherapeutic agent. However, the mechanisms of 6ME-induced cell death have not been investigated. The purpose of the present study was to determine the apoptosis-inducing potential of 6ME in ...

AIM: Hydrogen sulfide (H(2)S) is a prominent gaseous constituent of the gastrointestinal (GI) tract with known cytotoxic properties. Endogenous concentrations of H(2)S are reported to range between 0.2-3.4 mmol/L in the GI tract of mice and humans. Considering such high levels we speculate that, at non-toxic concentrations, H(2)S may interact ...

Poly(ADP-ribosyl) ation is a reversible post-translational protein modification implicated in the regulation of a number of biological functions. Whereas an 18 member superfamily of poly(ADP-ribose) polymerase (PARP) enzymes synthesize poly(ADP-ribose) (PAR), a single protein, PAR glycohydrolase (PARG) is responsible for the catabolism of the polymer. PARP-1 accounts for more than ...

1. Cardiotoxin (CTX) III is a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom. This is the first report on the mechanism of the anticancer effect of CTX III on human leukaemia K562 cells. 2. Cardiotoxin III was found to inhibit the growth of K562 ...

Poly(ADP-ribosyl)ation plays an important role in modulating the cellular response to stress. The extent of poly(ADP-ribosyl)ation, chiefly via the activation of the poly(ADP-ribose) polymerase-1 (PARP-1), correlates with the severity of genotoxic stress and this determines the cellular response. Under mild and moderate stress, it plays important roles in DNA processing ...

In many apoptosis pathways, activation of caspase-3 is considered the final stage. In this study, we studied PDT induced caspase-3 activation with fluorescence resonance energy transfer (FRET) technique. A recombinant caspase-3 substrate, SCAT3, was used as the FRET probe. FRET fluorescence images were collected after PDT or TNF-alpha induced apoptosis. ...

The relationship between aging and apoptosis remains unclear. We wondered whether apoptosis could be enhanced in arterial aging in the absence of overt or advanced arterial disease. Apoptosis-related proteins were investigated using three methods: TdT-mediated dUTP digoxigenin nick end labeling (TUNEL) technique, active cysteine-dependant aspartate specific proteases (caspase)-3 and poly ...

Cytokine stimulation induces proliferation and growth of acute myeloid leukemia (AML) blasts and high levels of cytokines have been associated with poor prognosis in AML. The Jak-Stat pathway constitutes a major mediator of cytokine activity. We investigated whether WP-1034, a novel Jak-Stat inhibitor, is active against AML blasts. OCIM2 and ...

HeLa and 16HBE14o(-) bronchial epithelium cells infected with human rhinovirus serotype 14 (HRV14) were found to exhibit typical apoptotic morphological alterations, such as cell contraction and nuclear condensation. These events coincided with high-molecular-weight DNA fragmentation, activation of caspase-9 and caspase-3 and poly(ADP-ribose) polymerase cleavage. Caspase activation was preceded by cytochrome ...

We investigated the possible mechanisms by which petrotetrayndiol A, a polyacetylene from the sponge Petrosia sp., exerts its anti-proliferative activity in cultured SK-MEL-2 human melanoma cells. Petrotetrayndiol A-treated SK-MEL-2 cells showed growth inhibition and induction of apoptosis in a dose-dependent manner as measured by MTT assay, fluorescent microscopy and flow ...

Paclitaxel has been found to exhibit cytotoxic and antitumor activity. There is little information regarding the mechanisms of apoptotic-inducing effect of paclitaxel on human osteogenic sarcoma U-2 OS cells. Several key regulatory proteins are involved in the initiation of apoptosis. Caspase-3 plays a direct role in proteolytic cleavage of cellular ...

A secreted cysteine protease (CP) fraction from Trichomonas vaginalis is shown here to induce apoptosis in human vaginal epithelial cells (HVEC) and is analyzed by mass spectrometry. The trichomonad parasite T. vaginalis causes one of the most common non-viral sexually transmitted infection in humans, trichomoniasis. The parasite as well as ...

Resveratrol (trans-3,4',5-trihydroxystilbene) is a naturally occurring polyphenolic compound highly enriched in grapes, peanuts, red wine, and a variety of food sources. Resveratrol has antiinflammatory and antioxidant properties, and also has potent anticancer properties. Human glioma U251 cells were used to understand the molecular mechanisms by which resveratrol acts as an ...

Ponicidin, an extract from the Chinese herb Rabdosia rubescens, is currently one of the most important traditional Chinese herbal medicines. Ponicidin has been reported to have anti-tumor effects on a large variety of malignant diseases. In this study, we investigated the anti-proliferation effects of ponicidin on human myeloid K562 and ...

Autocrine and paracrine mechanisms modulate the synthesis and secretion of extracellular matrix (ECM); moreover, each component of the ECM is capable of modulating the synthesis and release of other ECM molecules. Therefore, the synthesis of ECM glycoprotein fibronectin and laminin was studied in the human breast cancer cell lines MCF7 ...

PURPOSE: To test whether and how selenium enhances the apoptosis potency of selected chemotherapeutic drugs in prostate cancer (PCA) cells. EXPERIMENTAL DESIGN: DU145 and PC3 human androgen-independent PCA cells were exposed to minimal apoptotic doses of selenium and/or the topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin (SN38), the topoisomerase II inhibitor etoposide or ...

Apoptotic and autophagic cell death have been implicated, on the basis of morphological and biochemical criteria, in neuronal loss occurring in neurodegenerative diseases and it has been shown that they may overlap. We have studied the relationship between apoptosis and autophagic cell death in cerebellar granule cells (CGCs) undergoing apoptosis ...

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by deletions or mutations in the telomeric copy of the survival motor neuron (SMN1) gene. Although the SMN protein has been implicated in the biogenesis of ribonucleoprotein complexes and RNA processing, it is not clear how these functions contribute to the ...

Apoptosis competence is central to the prevention of cancer. Frequency of apoptotic cells, after a sample of colonic tissue is stressed, can be used to gauge apoptosis competence and, thus, possible susceptibility to colon cancer. The gold standard for assessment of apoptosis is morphological evaluation, but this requires an experienced ...

A novel substance, #675, found from an Streptomyces sp. SM675 culture medium, dose-dependently stimulates the proliferation of human functional liver cell 4 (FLC4). When FLC4 cells were incubated under conditions without fetal bovine serum (FBS), typical features of apoptotic cell death such as shrinkage and nuclear condensation appeared; high molecular ...

In this study, the MCF-7 breast cancer cells that lack caspase-3 were transfected with a wild type (WT) or mutant caspase-3 cDNA. Expression of the WT, but not of the mutant, caspase-3 was associated with increased caspase activity and susceptibility to staurosporine (STS)-induced apoptosis. Both derivatives displayed inhibition of cell ...

Cardiotoxin III (CTX III), a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom, has been reported to have anticancer activity. CTX III was found to inhibit the growth of K562 cells in a time-and dose-dependent manner with IC50 value of 1.7 microg/ml, and it displayed ...

Exposure to environmental mercury may be a factor that contributes to idiosyncratic autoimmune disease. Studies have demonstrated that inorganic, ionic mercury (i.e., Hg2+) modulates several lymphocyte signal transduction pathways, which may be a mechanism whereby Hg2+ dysregulates the immune response. The CD95/Fas apoptotic signaling pathway, which is of critical importance ...

On treatment with 7-ketocholesterol (7-keto) or 7beta-hydroxycholesterol (7beta-OH), which are major oxysterols in atherosclerotic plaques, the simultaneous identification of oncotic and apoptotic cells suggests that these compounds activate different metabolic pathways leading to various modes of cell death. With U937, MCF-7 (caspase-3 deficient), MCF-7/c3 cells (stably transfected with caspase-3), we ...

In the present study, we examined the molecular mechanism by which homocysteine causes neuronal cell apoptosis. We further investigated the mechanisms of melatonin's ability to reduce homocysteine-induced apoptosis. Consistent with its antioxidant properties, melatonin reduced homocysteine-induced lipid peroxidation and stimulated glutathione peroxidase enzyme activity in hippocampus of rats with hyperhomocysteinemia. ...

Sulfur mustard [SM; bis-(2-chloroethyl) sulfide], which causes skin blistering or vesication [(1991). Histo- and cytopathology of acute epithelial lesions. In: Papirmeister, B., Feister, A. J., Robinson, S. I., Ford, R. D., eds. Medical Defense Against Mustard Gas: Toxic Mechanisms and Pharmacological Implications. Boca Raton: CRC Press, pp. 43-78.], is a ...

Pseudolaric acid B is a major compound found in the bark of Pseudolarix kaempferi Gordon. In our study, pseudolaric acid B inhibited growth of human melanoma cells, A375-S2 in a time- and dose-dependent manner. A375-S2 cells treated with pseudolaric acid B showed typical characteristics of apoptosis including morphologic changes, DNA ...

The therapeutic goal in liver fibrosis is the reversal of fibrosis and the selective clearance of activated hepatic stellate cells (HSCs) by inducing apoptosis. Over the past several years, we have screened for natural products that mediate apoptosis in activated HSCs. Among the candidate compounds, honokiol, isolated from Magnoliae cortex, ...

Using in vitro model for studying the induction and inhibition of spontaneous apoptosis in human first trimester placental villi, mediated by the free radical scavenger SOD, we have examined the expression of bcl-xL, bax, Caspase-3 and PARP (Poly ADP-ribosyl). An increase in apoptosis was associated with activation of PARP and ...

Matrix metalloproteinases, like MMP-2 and MMP-9 gelatinases, show multiple functions as extracellular/cell-surface enzymes, and are broadly recognised for their matrix-degrading ability and involvement in cell motility. Given that adherent cells have reduced attachment during migration and also detach from their substratum during apoptosis, we now investigated whether extracellular matrix-bound gelatinases ...

BACKGROUND: We are attempting to elucidate the mechanism of apoptotic cell death induced by hypoxia in oral cancer cells. Since hypoxia can render solid tumors more resistant to radiation and chemotherapy, understanding the pathways involved in hypoxia-induced apoptosis of oral cancer cells would be of significant therapeutic value. RESULTS: Here ...

We have developed an oat cell-free apoptosis system to investigate the execution mechanisms of plant apoptosis. Cell extracts derived from oat tissues undergoing toxin (victorin)-induced apoptosis caused nuclear collapse and internucleosomal DNA fragmentation in isolated nuclei. Pharmacological studies revealed that cysteine protease, which is E-64-sensitive but insensitive to caspase-specific inhibitors, ...

Adenosylmethionine decarboxylase (AdoMetDC), a key enzyme in the biosynthesis of polyamines, is often up-regulated in cancers. We have demonstrated previously that overexpression of AdoMetDC alone is sufficient to transform NIH 3T3 cells and induce highly invasive tumors in nude mice. Here, we studied the transformation-specific alterations in gene expression induced ...

Protease inhibitor treatment strongly diminishes mortality in HIV-infected patients. This treatment has also been associated with lipodystrophy and has been shown to alter adipocyte differentiation. The protease inhibitor nelfinavir has been indirectly implicated in the appearance and development of lipodystrophic syndrome, as well as in adipocyte cell death. The aim ...

Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is the only non-steroidal anti-inflammatory drug so far which has been approved by the FDA for adjuvant treatment of patients with familial adenomatous polyposis. The molecular mechanism responsible for the anti-cancer effects of celecoxib is not fully understood. There is little data on the ...

PURPOSE: Unoprostone isopropyl is an ocular hypotensive that was originally produced as a prostaglandin F2alpha analogue and is eventually recognized as a synthetic docosanoid. The compound is recently suggested to have potent neuroprotective ability in the retina. The purpose of this study is to test whether and how the biologically ...