Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08758 (annexin V)
 9,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breast cancer is the most commonly diagnosed cancer among women in Western countries. Currently, there is no effective therapy for malignant estrogen-independent breast cancer. We have screened 38 species of edible mushroom on human estrogen-receptor positive (MCF-7) and estrogen-receptor negative (MDA-MB-231, BT-20) breast cancer cells to select potential agents with broad-spectrum antitumor activity against breast cancer cells. Water-based extracts of three mushroom species, Coprinellus sp., Coprinus comatus, Flammulina velutipes (CME, CCE and FVE, respectively), were identified as novel anti-breast cancer agents. The anti-tumor activities include: 1) marked growth inhibition of both ER+ and ER- breast cancer cells; 2) induction of rapid apoptosis on both ER+ and ER- cells; 3) significant inhibition of MCF-7 tumor colony formation in vitro. The antiproliferative and cytotoxic activities of the three mushroom extracts were dose-dependent, regardless of the hormone receptor status of the cancer cells. The degree of produced cytotoxicity on ER- breast cancer cells was very high, while the IC50 of mushroom extract CME was found to be as low as 40 microg/ml on MDA-MB-231 cells and the IC50 of mushroom extract FVE was only 30 microg/ml on BT-20 cells. More interestingly, mushroom extracts CME and FVE induced an exceptionally rapid apoptosis on MCF-7 and MDA-MB-231 detected by Annexin V-FITC within 2 h of treatment and DNA fragment end-labeling assay (TUNEL) in 5 h of treatment. Anchorage-independent growth assays indicated that the MCF-7 tumor colony formation rate was reduced by 60% in CCE- and CME-treated cells and nearly completely inhibited (99%) by FVE treatment. These results suggest that mushroom species Coprinus comatus, Coprinellus sp. and Flammulina velutipes contain potent antitumor compounds for breast cancer. Our finding is important due to the lack of chemotherapeutic and chemopreventive agents for ER- human breast cancer.
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PMID:In vitro effects on proliferation, apoptosis and colony inhibition in ER-dependent and ER-independent human breast cancer cells by selected mushroom species. 1639 63

The mechanisms underlying the cytotoxic action of pure fullerene suspension (nano-C60) and water-soluble polyhydroxylated fullerene [C60(OH)n] were investigated. Crystal violet assay for cell viability demonstrated that nano-C60 was at least three orders of magnitude more toxic than C60(OH)n to mouse L929 fibrosarcoma, rat C6 glioma, and U251 human glioma cell lines. Flow cytometry analysis of cells stained with propidium iodide (PI), PI/annexin V-fluorescein isothiocyanate, or the redox-sensitive dye dihydrorhodamine revealed that nano-C60 caused rapid (observable after few hours), reactive oxygen species (ROS)-associated necrosis characterized by cell membrane damage without DNA fragmentation. In contrast, C60(OH)n caused delayed, ROS-independent cell death with characteristics of apoptosis, including DNA fragmentation and loss of cell membrane asymmetry in the absence of increased permeability. Accordingly, the antioxidant N-acetylcysteine protected the cell lines from nano-C60 toxicity, but not C60(OH)n toxicity, while the pan-caspase inhibitor z-VAD-fmk blocked C60(OH)n-induced apoptosis, but not nano-C60-mediated necrosis. Finally, C60(OH)n antagonized, while nano-C60 synergized with, the cytotoxic action of oxidative stress-inducing agents hydrogen peroxide and peroxynitrite donor 3-morpholinosydnonimine. Therefore, unlike polyhydroxylated C60 that exerts mainly antioxidant/cytoprotective and only mild ROS-independent pro-apoptotic activity, pure crystalline C60 seems to be endowed with strong pro-oxidant capacity responsible for the rapid necrotic cell death.
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PMID:Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene. 1647 88

FMRFamide-related peptides are widespread neurotransmitters or neurohormones regulating somatic or visceral motor activity. Some recent data indicate that these neuropeptides may be involved in the control of cell proliferation and apoptosis. In this work we investigated the possible effect of FMRFamide on cell viability in an invertebrate-type proliferating tissue. As a model, we used the midintestinal gland of the snail, Helix lucorum Linnaeus. Immunohistochemistry demonstrated the direct innervation of the gland cells by FMRFamide-containing nerve fibers. Midintestinal glands of snails were injected with 50 microM FMRFamide and the control with sterile deionised water or bovine serum albumin (BSA). Injections were administrated 4 times. Transmission electron microscopy, annexin V-labeling, thiazolyl blue (MTT) viability tests and ploidy analyses were carried out to define the viable/dead cell ratio in the tissue samples. FMRFamide increased the MTT-reduction of tissues, reduced the amount of apoptotic nuclei and annexin V-labeled cells. Deionised water or BSA injection induced cell death. Cell cycle analysis revealed that FMRFamide significantly elevated the amount of cells in G0/G1 phase, but did not induce mitosis. We conclude, that the FMRFamide can be a life-signal for cells, protect them from apoptosis without altering mitosis.
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PMID:The neuropeptide FMRFamide can protect cells against apoptosis in the snail digestive gland. 1650 56

Coptidis rhizoma (C. rhizoma) had been demonstrated as an antioxidant and anticancer agent, however, its antioral cancer mechanism still remains unclear. Using water extracts of C. rhizoma, growth and apoptosis-related experiments for the treatment of multi-stage of oral cancer were carried out on immortalized human oral keratinocytes (IHOK), primary oral cancer cells (HN4), metastatic oral cancer cells (HN12) and human skin keratinocytes (HaCaT) by MTT assay, three-dimensional (3-D) raft cultures, western blotting, cell cycle analysis, nuclear staining and cytochrome c expression related to the apoptosis signaling pathway. C. rhizoma inhibited the proliferation of immortalized and malignant oral keratinocytes in a dose- and time-dependent manner. In 3-D organotypic culture, C. rhizoma-treated cells showed less maturation than the control cells, displaying low surface keratinization and decreased epithelial thickness. The major mechanism of growth inhibition by C. rhizoma appears to be the induction of apoptosis, which is supported by the results of the cell cycle analysis, FITC-annexin V staining, DNA fragmentation assay and DAPI staining. The induction of apoptosis by C. rhizoma was more prominent in immortalized keratinocytes than in malignant oral keratinocytes. Cytochrome-c release from mitochondria, accompanied by the activation of caspase-3, was observed in C. rhizoma-treated IHOK and oral cancer cells. These results suggest that C. rhizoma has apoptotic effects in immortalized and malignant oral keratinocytes via the mitochondrial signaling pathway.
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PMID:Extract of Coptidis rhizoma induces cytochrome-c dependent apoptosis in immortalized and malignant human oral keratinocytes. 1680 85

Twenty species of edible mushrooms and three purified mushroom polysaccharides were screened for their antitumor potential on human androgen-independent cancer PC-3 cells. A water-soluble extract (POE) prepared from the fresh oyster mushroom Pleurotus ostreatus produced the most significant cytotoxicity on PC-3 cells among the mushroom species tested. At the same time, POE induced a rapid apoptosis on PC-3 cells detected with annexin V-fluorescein isothiocyanate flow cytometry when the cells were exposed to POE (150 microg/mL) for 2 hours. Induced apoptosis was also confirmed by DNA fragment terminal deoxynucleotidyl transferase-mediated X-dUTP nick end labeling staining while POE (200 microg/mL) was added to PC-3 cells for 6 hours. Both cytotoxicity and induced apoptosis mediated by POE in PC-3 cells are dose-dependent. Interestingly, PC-3 cells appeared to be more sensitive to POE in anchorage-independent growth condition. Tumor colony-forming efficiency was dramatically reduced to 4.5% or 0.5% in POE (60 or 120 microg/mL)-supplemented soft agar medium compared with that of POE-free medium (defined as 100%). Temperature in POE processing plays a decisive role for the cytotoxic activity. Bioactivity of POE was eliminated by exposure to high temperature (80 degrees C) for 2 hours; however, it remained stable at a series temperatures of below 40 degrees C. The active fraction POE-F2 was analyzed and identified by size exclusion of high performance liquid chromatography and the CellTiter 96 AQueous Cell Proliferation Assay (Promega, Madison, WI). Since POE-F2 is also sensitive to heat and has strong 280 nm absorption, the results imply that active compounds recovered from P. ostreatus are water-soluble proteins or polypeptides.
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PMID:Cytotoxic effect of oyster mushroom Pleurotus ostreatus on human androgen-independent prostate cancer PC-3 cells. 1682 5

Advances in nanotechnology, in particular the development of novel types of nanoparticles, will result in advanced tools for biomedical research and clinical practice. One exciting aspect of future nanomaterial research will be the possibility to combine therapy and imaging in multifunctional nanoparticle designs. In this context, anisotropic particles with subcellular dimensions may offer so far unattainable capabilities, because they could provide access to directional information with respect to nanoparticle-cell interactions. We have recently developed an electrified jetting process, which can produce water-stable polymer particles with two distinct phases. To address the first critical hurdle towards the application of these biphasic nanocolloids as imaging probes, short-term biocompatibility was evaluated using model cell culture systems. Exposure of human endothelial cells and murine fibroblasts to biphasic nanocolloids made of 0.5% polyacrylic acid and 4.5% poly(acrylamide-co-acrylic acid) did not affect cell proliferation as determined by a colorimetric proliferation assay. Moreover, double staining with Annexin V and propidium iodide and subsequent flow cytometric analysis indicated high cell viability, although slightly decreased viability was observed at the highest dose tested (1mg particles/10(6) seeded cells). Particle internalization as well as surface binding occurred simultaneously for both cell types, as evidenced by confocal laser scanning microscopy. Taken together, these results suggest excellent short-term biocompatibility in physiological systems for wide concentration ranges of the biphasic nanocolloids and open possibilities for future work investigating receptor- or surface marker-mediated targeting.
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PMID:Short-term biocompatibility of biphasic nanocolloids with potential use as anisotropic imaging probes. 1733 97

Fluoride is found in the atmosphere, water, soil, coal, food, dental and industrial uses. There were some case reports concerning acute fluoride poisoning in workplaces and laboratories. However, there is limited information concerning the mechanism of fluoride-induced cell death. To study the cytotoxicity of fluoride, the effect of sodium fluoride (NaF) on rat thymocytes has been examined by using a flow cytometer with appropriate fluorescence probes for membrane and cellular parameters. The cytotoxicity of NaF under nominal Ca2+-free condition was significantly lower than that under control condition. NaF also increased intracellular Ca2+ concentration. NaF significantly increased the population of shrunken cells and the cells positive to annexin V. Both are known to be parameters for early stage of apoptosis. However, NaF decreased the population of cells with hypodiploidal DNA, indicating that NaF apparently attenuated spontaneous apoptosis in rat thymocytes. It may be suggested that NaF induces necrosis, associated with some apoptotic characteristics.
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PMID:Some characteristics of fluoride-induced cell death in rat thymocytes: cytotoxicity of sodium fluoride. 1754 15

Leishmaniasis remains a major health problem of the tropical and subtropical world. The visceral form causes the most fatalities if left untreated. Dramatic increases in the rates of infection and drug resistance and the non-availability of safe vaccines have highlighted the need for identification of novel and inexpensive anti-leishmanial agents. This study reports that racemoside A, a water-soluble steroidal saponin purified from the fruits of Asparagus racemosus, is a potent anti-leishmanial molecule effective against antimonial-sensitive (strain AG83) and -unresponsive (strain GE1F8R) Leishmania donovani promastigotes, with IC(50) values of 1.15 and 1.31 microg ml(-1), respectively. Incubation of promastigotes with racemoside A caused morphological alterations including cell shrinkage, an aflagellated ovoid shape and chromatin condensation. This compound exerts its leishmanicidal effect through the induction of programmed cell death mediated by the loss of plasma membrane integrity as detected by binding of annexin V and propidium iodide, loss of mitochondrial membrane potential culminating in cell-cycle arrest at the sub-G(0)/G(1) phase, and DNA nicking shown by deoxynucleotidyltransferase-mediated dUTP end labelling (TUNEL). Racemoside A also showed significant activity against intracellular amastigotes of AG83 and GE1F8R at a 7-8-fold lower dose, with IC(50) values of 0.17 and 0.16 microg ml(-1), respectively, and was non-toxic to murine peritoneal macrophages up to a concentration of 10 microg ml(-1). Hence, racemoside A is a potent anti-leishmanial agent that merits further pharmacological investigation.
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PMID:Racemoside A, an anti-leishmanial, water-soluble, natural steroidal saponin, induces programmed cell death in Leishmania donovani. 1776 83

The purpose of this article is to present the current state of knowledge regarding the structure and functions of articular cartilage. Articular cartilage is constructed with hyaline cartilage tissue. It is composed of chondrocytes located in lacunae and the extracellular matrix. The chondrial matrix contains water, collagen, proteglycans, non-collagenous matrix proteins, and lipids. Articular cartilage is devided into four zones - superficial, intermediate, deep, and calcified - on the basic of morphology, the orientation of collagen fiber, and the proteoglycan content. The dominant collagen of this tissue is Type II collagen, which, together with smaller quantities of other collagens (i.e. Types IX and XII), forms a network of fibers, with large, aggregating proteoglycans and smaller, non-aggregating proteoglycans. Proteoglycans are proteins that contain covalently attached glycosaminoglycans (GAGs), with water between them. The large aggregating proteoglycans, called "aggrecans", form aggregates that bind hyaluronic acid, and together with collagen they are responsible for the mechanical properties of cartilage. The smallnonaggregating proteoglycans, decorin and fibromodulin, limit the formation of collagen fibres. Other proteins in the cartilage matrix - chondrocalcin and the N-propetide of Type II collagen - participate in fiber formation. Yet other proteins - chondronectin, fibronectin, vitronectin and thrombospondin - take part in the interaction between the chondrocytes and the matrix. Cartilage oligomeric matrix protein (COMP) prevents the vascularization of the cartilage and, perhaps, is responsible for the repair process. The proteins known as Cart-1 and CEP-68 participate in chondrogenesis, while tenascin and Mgp are considered to be cartilage calcification inhibitors. Apart from the structural elements, chondrocytes produce substances that fulfill purely physiological functions: enzymes and cytokines. The enzymes - which include metalloproteinases, adamalysins, serine and cysteine proteases and their inhibitors - participate in cartilage matrix reconstruction. The cytokines - IL-1, TNF-alfa, IL-6, IL-8, and LIF - stimulate the chondrocytes to produce an increased amount of enzymes, while IL-4 inhibits this process. Human articular chondrocytes exibit the constitutive expression of class I molecules of the major histocompatibility complex (MHC), molecules regulating the activation of the complement, and after activation (e.g. under the influence of IFN-alfa, IL-1, TNF-a or in the course of arthritis), also MHC class II and ICAM-1 intracellular adhesion molecules. Numerous studies have shown that chondrocytes also have tissue-specific antigens, which induce the production of antibodies in patients with cartilage grafts, as well as those with rheumatoid arthritis and osteoarthritis. Some of these antibodies react with type II collagen, others are directed against other proteins i.e. anchorin CII and CH65. the role of these diverse molecules, which are present in cartilage cells and separated from the immune system by the matrix, remains unclear.
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PMID:The morphology and selected biological properties of articular cartilage. 1798 77

We report here a novel bioprobe based on Rhodamine B isothiocyanate doped silica-coated fluorescent nanoparticles (RBITC-DSFNPs) for early-stage apoptosis detection and imaging. RBITC-DSFNPs were constructed by synchronous hydrolysis of APTES-RBITC and tetraethoxysilane in water-in-oil microemulsion, and the bioprobes were prepared through modifying Annexin V with RBITC-DSFNPs. The characterization of RBITC-DSFNPs and the bioprobes' application for apoptosis detection and imaging were investigated. It was demonstrated that RBITC-DSFNPs are uniform and possess excellent photostability. The bioprobes could specifically recognize early-stage apoptotic cells through the binding between Annexin V and phosphatidylserine (the externalization of which from the inner to the outer membrane is an early and major event in the apoptotic process) on the outer membrane of apoptotic cells. Moreover, the RBITC-DSFNPs labeling method was also used to monitor the increase of the number of early-stage apoptotic cells along with the extended induction time. Compared with the conventional fluorochrome such as Cy3-labeled Annexin V for staining apoptotic cells, the RBITC-DSFNPs labeling method possesses much better photostability, which offers a promising approach for tumor-related research.
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PMID:Rhodamine B isothiocyanate doped silica-coated fluorescent nanoparticles (RBITC-DSFNPs)-based bioprobes conjugated to Annexin V for apoptosis detection and imaging. 1798 54


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