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)

Hydantoin derivatives possess a variety of biochemical and pharmacological properties and consequently are used to treat many human diseases. However, there are only few studies focusing on their potential as cancer therapeutic agents. In the present study, we have examined anticancer properties of two novel spirohydantoin compounds, 8-(3,4-difluorobenzyl)-1'-(pent-4-enyl)-8-azaspiro[bicyclo[3.2.1] octane-3,4'-imidazolidine]-2',5'-dione (DFH) and 8-(3,4-dichlorobenzyl)-1'-(pent-4-enyl)-8-azaspiro[bicyclo[3.2.1]octane-3,4'-imidazolidine]-2',5'-dione (DCH). Both the compounds exhibited dose- and time-dependent cytotoxic effect on human leukemic cell lines, K562, Reh, CEM and 8E5. Incorporation of tritiated thymidine ([(3)H] thymidine) in conjunction with cell cycle analysis suggested that DFH and DCH inhibited the growth of leukemic cells. Downregulation of PCNA and p-histone H3 further confirm that the growth inhibition could be at the level of DNA replication. Flow cytometric analysis indicated the accumulation of cells at subG1 phase suggesting induction of apoptosis, which was further confirmed and quantified both by fluorescence-activated cell sorting (FACS) and confocal microscopy following annexin V-FITC/propidium iodide (PI) staining. Mechanistically, our data support the induction of apoptosis by activation of the mitochondrial pathway. Results supporting such a model include, elevated levels of p53, and BAD, decreased level of BCL2, activation and cleavage of caspase 9, activation of procaspase 3, poly (ADP-ribosyl) polymerase (PARP) cleavage, downregulation of Ku70, Ku80 and DNA fragmentation. Based on these results we discuss the mechanism of apoptosis induced by DFH and its implications in leukemia therapy.
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PMID:Novel derivatives of spirohydantoin induce growth inhibition followed by apoptosis in leukemia cells. 1901 9

Methyl angolensate (MA), a natural tetranortriterpenoid, purified from Soymida febrifuga is examined for the first time for its anticancer properties. We find that MA inhibits growth of T-cell leukemia and chronic myelogenous leukemia cells in a time- and dose-dependent manner. Accumulation of cells in the subG1 peak, annexin V binding and DNA fragmentation suggested induction of apoptosis. Besides, upregulation of BAD (proapoptotic) and downregulation of BCL2 (antiapoptotic) gene products further supported induction of apoptosis. Loss of mitochondrial membrane potential, activation of caspase 9, caspase 3, cleavage of PARP, downregulation of Ku70/80 and phosphorylation of MAP kinases suggested that MA could induce intrinsic pathway of apoptosis in leukemic cells.
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PMID:Methyl angolensate, a natural tetranortriterpenoid induces intrinsic apoptotic pathway in leukemic cells. 1902 52

Mild temperatures such as 40 degrees C are physiological and occur during fevers. This study determines whether mild thermotolerance induced at 40 degrees C can protect HeLa cells against activation of the death receptor pathway of apoptosis by lethal hyperthermia (42-45 degrees C). Protein expression of heat shock proteins (Hsps) 27, 32, 60, 72, 90, and 110 was increased in thermotolerant cells (3 h, 40 degrees C). Lethal hyperthermia (42-43 degrees C) caused cell death by apoptosis, but at 45 degrees C there was a switch to necrosis. Mild thermotolerance protected cells against heat-induced apoptosis (Annexin V labelling). Hyperthermia induced apoptosis through generation of reactive oxygen species (ROS) and death receptor signalling. The antioxidant polyethylene glycol-catalase abrogated increased expression of Fas death ligand and caspase-8 activation in response to lethal hyperthermia (42-43 degrees C). Mild thermotolerance attenuated the heat induction of ROS and FasL, which were initiating events in death receptor activation and signalling. Mild thermotolerance inhibited early events in hyperthermia-induced death receptor apoptosis such as Fas-associated death domain (FADD) translocation to membranes, caspase-8 activation, and tBid translocation to mitochondria. Downstream events in apoptosis such as caspase-3 activation, cleavage of PARP and ICAD, and chromatin condensation were also diminished in thermotolerant cells. It is important to improve knowledge about adaptive responses induced by exposure to mild stresses, such as fever temperatures, which can protect cells against subsequent exposure to lethal stress.
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PMID:Thermotolerance induced at a fever temperature of 40 degrees C protects cells against hyperthermia-induced apoptosis mediated by death receptor signalling. 1908

The mechanism of apoptosis induced by SIRT1 deacetylase inhibitors in both human breast cancer MCF-7 and MCF-7 doxorubicin-resistant cells was studied. MTT assay was used to detect growth-inhibitory effect on the cells. Protein expression was detected by Western blotting. Chromatin condensation was detected by a fluorescent microscope after Hoechst 33342 staining. Cell cycle distribution was analyzed with flow cytometry. Apoptotic cells were detected with Annexin V staining. Nicotinamide (NAM) and Sirtinol, two SIRT1 deacetylase inhibitors, exhibited the similar growth-inhibitory effects on MCF-7/DOX cells and MCF-7 cells, but no potentiation of DOX activities. The arrest at G2/M phase was detected by flow cytometry in both MCF-7 and MCF-7/DOX cells after NAM treatment. Activation of caspase pathway in MCF-7 cells, such as the cleavages of PARP, caspase-6, -7, -9, were observed after exposure to NAM 50 mmol x L(-1), accompanied by the occurrence of chromatin condensation and Annexin V positive cells. However, the cleavages of PARP, caspase-6 and -7 in MCF-7/DOX cells delayed after exposure to NAM for 24 h and obviously increased at 48 h with appearance of chromatin condensation and Annexin V positive cells. SIRT1 deacetylase inhibitors show no cross resistance to MCF-7 drug-resistant cells, and the similar growth-inhibitory actions of them to MCF-7 sensitive and drug-resistant cells by which it is mediated by activation of apoptotic caspase pathway.
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PMID:[Mechanism of apoptosis induced by SIRT1 deacetylase inhibitors in human breast cancer MCF-7 drug-resistant cells]. 1912 63

Oroxylin A is a flavonoid that is found in the roots of Scutellaria baicalensis Georgi. Here, we investigated the antitumor effect of oroxylin A in human cervical cancer HeLa cell line in vitro and in vivo. We found that after inoculated with the HeLa cells the mice treated with oroxylin A showed a significant decrease of tumor volumes and tumor weight compared with the control. Meanwhile, the growth inhibition of oroxylin A on HeLa cells were observed by MTT assay and the value of IC(50) was 19.4+/-0.7 microM after treatment for 48h. Upon our previous research, the inhibition by oroxylin A might be through apoptosis. Then apoptosis induced by oroxylin A in HeLa cells was characterized by DAPI staining and Annexin V/PI double staining, and degradation of PARP (poly-ADP-ribose polymerase) was both found in HeLa cells and tumor tissue. Next, activation of the caspase cascade for both the extrinsic and intrinsic pathways were demonstrated in vivo and in vitro, including caspase-8, -9 and -3. We also found that the expression of Bcl-2 protein decreased, which leading to an increase of the Bax/Bcl-2 ratio. Our results showed that oroxylin A exhibited strong antitumor effect in HeLa cell line and apoptosis induction involved in it.
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PMID:Apoptosis induction of oroxylin A in human cervical cancer HeLa cell line in vitro and in vivo. 1913 24

DNA intercalators are one of the most commonly used chemotherapeutic agents. Novel intercalating compounds of pyrimido[4',5':4,5]selenolo(2,3-b)quinoline series having a butylamino or piperazino group at fourth position (BPSQ and PPSQ, respectively) are studied. Our results showed that BPSQ induced cytotoxicity whereas PPSQ was cytostatic. The cytotoxicity induced by BPSQ was concentration- and time-dependent. Cell cycle analysis and tritiated thymidine assay revealed that BPSQ affects the cell cycle progression by arresting at S phase. The absence of p-histone H3 and reduction in the levels of PCNA in the cells treated with BPSQ further confirmed the cell cycle arrest. Further, annexin V staining, DNA fragmentation, nuclear condensation and changes in the expression levels of BCL2/BAD confirmed the activation of apoptosis. Activation of caspase 8 and lack of cleavage of caspase 9, caspase 3 and PARP suggest the possibility of BPSQ triggering extrinsic pathway for induction of apoptosis, which is discussed. Hence, we have identified a novel compound which would have clinical relevance in cancer chemotherapeutics.
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PMID:A novel DNA intercalator, butylamino-pyrimido[4',5':4,5]selenolo(2,3-b)quinoline, induces cell cycle arrest and apoptosis in leukemic cells. 1914 83

Pyrogallol, a catechin compound, is an active component of Emblica officinalis extracts and has an anti-proliferative effect on some human cancer cell lines. In our preliminary study, pyrogallol had highly cytotoxic effect on human lung cancer cell lines and less effect on human bronchial epithelium cell line. This study was performed to investigate the beneficial effect of pyrogallol on human lung cancer cell lines - H441 (lung adenocarcinoma) and H520 (lung squamous cell carcinoma). The MTT (cytotoxic) data showed the inhibition growth of lung cancer cells followed pyrogallol treatment. The cell cycle of lung cancer cells was arrested in G2/M phase using flow cytometry. Using Western blot analysis, the cell cycle related proteins - cyclin B1 and Cdc25c were decreased in a time-dependent manner and the phosphorylated Cdc2 (Thr14) was increased within 4h pyrogallol treatment. Moreover, the higher cleavage of poly (ADP)-ribose polymerase (PARP), the increased of Bax concurrent with the decreased of Bcl-2 indicated that pyrogallol treatment resulted in apoptosis of lung cancer cells. The cell apoptosis was also directly demonstrated using Annexin V-FITC and TUNEL stain. Additionally, the tumoricidal effect of pyrogallol was measured using a xenograft nude mice model. After 5 weeks of pyrogallol treatment could cause the regression of tumor. Taken in vitro and in vivo studies together, these results suggest that pyrogallol can be developed as a promising anti-lung cancer drug particular for the non-small cell lung cancer (NSCLC).
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PMID:Pyrogallol induces G2-M arrest in human lung cancer cells and inhibits tumor growth in an animal model. 1923 5

The aim of this study was to investigate apoptotic effect of 2-methoxyestradiol (2-ME2) on K562 cells and its mechanism. K562 cells were treated with different concentrations of 2-ME2. MTT assay was used to examine the effect inducing growth inhibition. DNA fragmentation assay and Annexin V-FITC/PI staining were used to detect the effect of apoptosis. The change of mitochondrial transmembrane potential was analyzed by flow cytometry. The expressions of related gene mRNA and/or proteins were detected by RT-PCR and Western blot respectively. The results indicated that the 2-ME2 inhibited proliferation of K562 cells in a time- and dose-dependent manners and the concentration of 50% growth inhibition (IC(50)) was 2 micromol/L at 48 hours. 2-ME2 induced DNA ladder and significantly increased apoptosis in K562 cells when exposed to 2 micromol/L of 2-ME2 for 24, 48 and 72 hours, the result of Annexin-V/PI staining showed that rates of the apoptotic cells were 13.78%, 22.32% and 29.43% respectively, which was remarkably higher than that of control (1.78%) (p < 0.05). The FCM analysis showed that the mitochondrial transmembrane potential in K562 cells lowered after exposed to 1, 2 and 4 micromol/L of 2-ME2 for 24 hours. 2-ME2 down-regulated the expression of bcr/abl and bcl-2, up-regulated the expression of bax mRNA, and down-regulated protein expressions of bcl-2, procaspase-3, procaspase-9, PARP (116 kD) and p-Akt, and up-regulated expression of cytoplasmic Cyto-C and PARP 85 kD apoptosis-related cleavage fragment protein, but had no effect on total Akt protein in K562 cells after treated with 2 micromol/L of 2-ME2 for 24, 48 and 72 hours. It is concluded that the 2-ME2 can induce the apoptosis and inhibit the proliferation of K562 cells by increasing the ratio of bax/bcl-2, reducing the mitochondrial transmembrane potential, releasing cytochrome C to cytoplasm, initiating the mitochondrial apoptosis pathway and leading in turn to caspase-3 activation. These findings suggest that interfere PI3K/Akt signal pathway via down-regulating the expression of bcr/abl mRNA is implicated in the effect of 2-ME2 on K562 cells.
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PMID:[Mechanism underlying 2-methoxyestradiol inducing apoptosis of K562 cells]. 1937 63

Astragalus membranaceus has been used to ameliorate the side effects of antineoplastic drugs because of its immunomodulating nature. We had recently demonstrated that total Astragalus saponins (AST) possess anticarcinogenic and proapoptotic properties in human colon cancer cells and tumor xenograft. In this study, we identified NSAID-activated gene (NAG-1) as a potential molecular target of AST. The growth-inhibitory and proapoptotic effects of AST were assessed in a panel of human cancer cell lines. Hoechst 33342 nuclear staining, Annexin V-FITC/propidium iodide staining, Western immunoblotting, real-time PCR, luciferase reporter assay and electrophoretic mobility shift assay were conducted to determine the association of NAG-1 and related transcription factors with AST during its regulation of apoptotic activities. Moreover, the combined proapoptotic and NAG-1 promoting activities of AST and/or inhibitors of the PI3K-Akt pathway were also examined. AST caused overexpression of NAG-1, leading to PARP cleavage and apoptosis. The induction of NAG-1 promoter activity by the drug was associated with increased gene expression, in addition to prior increase in Egr-1 expression and DNA binding activity. AST-induced NAG-1 activation was intensified when PI3K inhibitor LY294002 or Akt inhibitor was co-treated and reversed by NAG-1 siRNA transfection. Nevertheless, the extent of NAG-1 induction could not be altered by the ERK inhibitor PD98059. Our results indicate that NAG-1 is a potential molecular target of AST in its antitumorigenic and proapoptotic actions, which would have additive effects when used along with PI3K-Akt inhibitors. The information obtained could facilitate future development of a novel target-specific chemotherapeutic agent with known molecular pathway.
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PMID:A novel anticancer effect of Astragalus saponins: Transcriptional activation of NSAID-activated gene. 1938 47

Macranthoside B (MB) is a hederagenin saponin extracted from the flower bud of Lonicera macranthoides. In this study, we defined the anticancer effect of MB both in vitro and in vivo using cell proliferation assays and xenograft tumor growth assays. Our data indicate that MB inhibits the proliferation of various kinds of cancer cells with IC(50) values in the range of 10-20 microM. Moreover, the volume and weight of xenograft tumors in nude mice treated with 5mg/kgMB were decreased remarkably compared to those of the vehicle control group. Furthermore, DAPI staining and flow cytometry analysis with Annexin V/PI double staining revealed that more apoptotic cells were observed following MB treatment. In addition, degradation of PARP (poly-ADP-ribose polymerase), and activation of the caspase cascade for intrinsic pathways were observed. We also found that the expression of Bcl-2 protein decreased and the protein level of Bax increased which leading to an increase of the Bax/Bcl-2 ratio. Our results showed that MB exhibited strong anti-tumor effect and mitochondrion-mediated apoptosis induction involved in it.
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PMID:Macranthoside B, a hederagenin saponin extracted from Lonicera macranthoides and its anti-tumor activities in vitro and in vivo. 1940 96


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