Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.22.56 (caspase-3)
35,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sungucine and isosungucine are two bisindole alkaloids isolated from the roots of the African plant Strychnos icaja Baillon. They both exhibit antiplasmodial activities but also show cytotoxic effects against human cancer cell lines. In order to elucidate their mechanism of action, we have investigated the interaction of the alkaloids with DNA and their capacity to inhibit nucleic acids and protein synthesis in the human HL-60 promyelocytic leukemia cell line. Cell treatment with both sungucine and isosungucine leads to the appearance of a hypo-diploid DNA content peak. Western blotting analysis reveals that the two alkaloids induce cleavage of the poly(ADP-ribose) polymerase (PARP) and promote the cleavage of a caspase-3 DEVD peptide substrate. The activation of the caspase cascade is accompanied with a fragmentation of DNA in cells, as revealed by the TUNEL assay. Altogether, the results shed light on the mechanism of action of these two plant alkaloids and identify signaling factors involved in (iso)sungucine-induced apoptosis in HL-60 cells.
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PMID:Apoptosis of HL-60 leukemia cells induced by the bisindole alkaloids sungucine and isosungucine from Strychnos icaja. 1214 90

We studied the effect of momordin I, a compound purified from a plant, Ampelopsis japonica, on cell proliferation and induction of apoptosis in human promyelocytic leukemia (HL-60) cells. Momordin I was cytotoxic to HL-60 cells with an IC50 of 19.0 microg/ml. The antiproliferative effects of momordin I appear to be attributable to its induction of apoptotic cell death, as momordin I induced nuclear morphology changes and internucleosomal DNA fragmentation and it increased the proportion of hypodiploid cells. Momordin I treatment also gradually decreased the expression of.the anti-apoptotic protein Bcl-2, but increased the expression of the pro-apoptotic protein Bax. In addition, momordin I treatment increased the activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase. In this study we showed that momordin I induced apoptosis of HL-60 cells by reduction of the Bcl-2:Bax ratio and by activation of caspase-3. These results provide important information towards understanding the mechanism by which momordin I induces apoptosis.
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PMID:Induction of apoptosis by momordin I in promyelocytic leukemia (HL-60) cells. 1216 88

Recently, it was suggested the potential role of gamma-tocopheryl quinone (gamma-TQ), an oxidative metabolite of gamma-tocopherol, as a powerful chemotherapeutic agent, since it was shown that this molecule exerts powerful cytotoxic effects, induces apoptosis and escapes drug resistance in human acute lymphoblastic leukemia and promyelocytic leukemia cells. We have studied the apoptogenic potential of gamma-TQ in cultured human leukemia HL-60 and colon adenocarcinoma WiDr cells, and in murine thymoma cells growing in vivo in ascites form. The cells were treated with gamma-TQ and apoptosis was evaluated morphologically by acridine-orange staining and cytofluorimetrically by Annexin V binding assay. gamma-TQ-induced apoptosis in a dose- and time-dependent manner in all the cell types tested, although HL-60 and thymoma cells were much more sensitive than WiDr cells. In HL-60 cells apoptosis was mediated by the activation of the caspase-3 cascade. In particular, we observed a time- and dose-dependent increase in the activities of the upstream caspase-9 and caspase-8 and of the downstream caspase-3. The activation of caspase-9 preceded that of caspase-8 and its specific inhibition completely prevented apoptosis. These findings and data showing the precocious release of cytochrome c from mitochondria, a decrease in Bcl-2, and a change in mitochondrial transmembrane potential (Delta psi(m)), all suggest that the intrinsic mitochondrial pathway is primarily involved in the development of gamma-TQ-induced apoptosis. The late activation of caspase-8 and data showing the partial cleavage of pro-apoptotic protein BID suggest that the initial activation of caspase-9 may be potentiated by a feedback amplification loop involving the caspase-8/BID pathway.
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PMID:gamma-Tocopheryl quinone induces apoptosis in cancer cells via caspase-9 activation and cytochrome c release. 1266 1

Herba houttuyniae has been used as a constituent of herval medicine prescriptions for the treatment of inflammation, cancer, and other diseases. In the present study, we investigated the cellular effects of herba houttuyniae extract (HHE) and the signal pathways of HHE-induced apoptosis in HL-60 human promyelocytic leukemia cell line. HHE treatment caused apoptosis of cells as evidenced by discontinuous fragmentation of DNA, the loss of mitochondrial membrane potential, release of mitochondrial cytochrome c into the cytosol, activation of procaspase-9 and caspase-3, and proteolytic cleavage of poly(ADP-ribose) polymerase. Pretreatment of Ac-DEVD-CHO, caspase-3 specific inhibitor, or cyclosporin A, a mitochondrial permeability transition inhibitor, completely abolished HHE-induced DNA fragmentation. Together, these results suggest that HHE possibly causes mitochondrial damage leading to cytochrome c release into cytosol and activation of caspases resulting in PARP cleavage and execution of apoptotic cell death in HL-60 cells.
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PMID:Herba houttuyniae extract induces apoptotic death of human promyelocytic leukemia cells via caspase activation accompanied by dissipation of mitochondrial membrane potential and cytochrome c release. 1275 12

Anthocyanidins are the aglycon nucleuses of anthocyanins, which are reddish pigments widely spread in colored fruits and vegetables. To investigate their anti-cancer effect, induction of apoptosis was tested in human promyelocytic leukemia cells (HL-60), which is a valid model for testing antileukemic or general antitumoral compounds. Of six anthocyanidins representing the aglycons of most of anthocyanins, only those with an ortho-dihydroxyphenyl structure on the B-ring induce apoptosis, suggesting that the ortho-dihydroxyphenyl structure of anthocyanidins may contribute to the induction of apoptosis. Delphinidin, the most potent inducer, causes apoptosis in a time- and dose-dependent manner. The efficacious induction of apoptosis was observed at 100 micro M for 6 h. Concomitant with the apoptosis, delphinidin stimulates JNK pathway activation including JNK phosphorylation and c-jun gene expression, and activates caspase-3. Antioxidants including N-acetyl-L-cysteine (NAC) and catalase effectively block delphinidin-induced JNK phosphorylation, caspase-3 activation, and DNA fragmentation. Moreover, anthocyanidins directly cause HL-60 cells to generate intracellular hydrogen peroxide. Thus, anthocyanidins may trigger an apoptotic death program through an oxidative stress-involved JNK signaling pathway. The induction of apoptosis by anthocyanins may be the pivotal mechanism by which its chemopreventive action against cancer is based.
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PMID:Anthocyanidins induce apoptosis in human promyelocytic leukemia cells: structure-activity relationship and mechanisms involved. 1288 7

Caspases have been shown to play a crucial role in apoptosis induced by various deleterious and physiologic stimuli. In this study, we show for the first time that photodynamic therapy (PDT), using benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) as the photosensitizer, induces the complete cleavage and subsequent activation of caspase-3 (CPP32/Yama/Apopain) but not caspase-1 (ICE) in human promyelocytic leukemia HL-60 cells. Poly(ADP-ribose) polymerase (PARP) and the catalytic subunit of DNA dependent protein kinase (DNA PK(CS)) were cleaved within 60 min of light activation of BPD-MA. The general caspase inhibitor Z-Asp-2,6 dichlorobenzoyloxymethylketone (Z-Asp-DCB) blocked PARP cleavage while the serine protease inhibitors 3,4-dichloroisocoumarin (DCI) and N-tosyl-lysyl chloromethyl ketone (TLCK) blocked the cleavage of caspase-3 suggesting that they act upstream of caspase-3 activation. All three inhibitors were able to block DNA fragmentation that was induced by treatment with BPD-MA followed by light application. These studies demonstrate that protease activity, particularly that of caspase-3, is triggered in HL-60 cells treated with lethal levels of BPD-MA and visible light.
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PMID:Photodynamic therapy induces caspase-3 activation in HL-60 cells. 1455 76

In this study, we evaluated the potential apoptosis effects of baicalein on human promyelocytic leukemia HL-60 cells in vitro. Apoptosis induction, cell viability, morphology and caspase-3 activity were then performed to determine by flow cytometric assay, DNA gel electrophoresis, anti-ADP-ribose stain and determination of caspase-3 activity. There is a significant difference in cell death of HL-60 cells that was detected between baicalein-treated and untreated groups. Furthermore, there was a further significant increase in apoptosis induction when cells were treated with baicalein compared to without baicalein treated groups. Flow cytometric assays and DNA fragmentation gel electrophoresis also confirmed baicalein induced apoptosis in HL-60 cells. Baicalein also promoted caspase-3 activity then leading to cleavage of poly-ADP-ribose polymerase finally leading to DNA fragmentation occurrence. Furthermore, the baicalein-induced apoptosis was markedly blocked by the broad-spectrum caspase inhibitor, z-VAD-fmk. Taken together, these results suggest that treatment of human leukemia HL-60 cells with baicalein induced apoptosis through activation of caspase-3 activity.
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PMID:Baicalein induced in vitro apoptosis undergo caspases activity in human promyelocytic leukemia HL-60 cells. 1463 Jan 28

Vitamin K-related analogs induce growth inhibition via a cell cycle arrest through cdc25A phosphatase inhibition in various cancer cell lines. We report that 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (DDN), a naphthoquinone analog, induces mitochondria-dependent apoptosis in human promyelocytic leukemia HL-60 cells. DDN induced cytochrome c release, Bax translocation, cleavage of Bid and Bad, and activation of caspase-3, -8, -9 upon the induction of apoptosis. Cleavage of Bid, the caspase-8 substrate, was inhibited by the broad caspase inhibitor z-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk), whereas cytochrome c release was not affected, suggesting that activation of caspase-8 and subsequent Bid cleavage occur downstream of cytochrome c release. DDN inhibited the activation of Akt detected by decreasing level of phosphorylation. Overexpression of constitutively active Akt protected cells from DDN-induced apoptosis, while dominant negative Akt moderately enhanced cell death. Furthermore, Akt prevented release of cytochrome c and cleavage of Bad in DDN-treated HL-60 cells. Taken together, DDN-induced apoptosis is associated with mitochondrial signaling which involves cytochrome c release via a mechanism inhibited by Akt.
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PMID:Involvement of Akt in mitochondria-dependent apoptosis induced by a cdc25 phosphatase inhibitor naphthoquinone analog. 1464 18

The antioxidant and anticancer properties of a medicinal plant, Betula platyphylla var. japonica were investigated. The total methanol extract of B. platyphylla var. japonica had protective effects against hydrogen peroxide (H2O2) in the Chinese hamster lung fibroblast (V79-4) cell line and induced apoptotic cell death in human promyelocytic leukemia (HL-60) cells, a cancer cell line. B. platyphylla var. japonica extract significantly increased cell viability against H2O2. The extract also showed high 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (IC50 2.4 microg/ml) and lipid peroxidation inhibitory activity (IC50 below 4.0 microg/ml). Furthermore, B. platyphylla var. japonica extract reduced the number of V79-4 cells arrested in G2/M in response to H2O2 treatment and increased the activities of several cellular antioxidant enzymes, including superoxide dismutase, catalase and glutathione peroxidase. Treatment with B. platyphylla var. japonica extract induced cytotoxicity and apoptosis in HL-60 cells, as shown by nucleosomal DNA fragmentation, increases in the subdiploid cell population, and fluorescence microscopy. B. platyphylla var. japonica extract gradually increased the expression of pro-apoptotic Bax and led to the activation of caspase-3 and cleavage of PARP. These findings suggest that B. platyphylla var. japonica exhibits potential antioxidant and anticancer properties.
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PMID:Antioxidant and anticancer activity of extract from Betula platyphylla var. japonica. 1467 57

In this paper we report the isolation and structural elucidation of a new flavonoid (1) and three known compounds, 6,8-di-C-methylkaempferol 3-methyl ether (2), oleanolic acid, and 2 alpha,3 beta-dihydroxyurs-12-en-28-oic acid, from aerial parts of Eucalyptus occidentalis collected in Algeria. Flavonoids 1 and 2 were used to study their biological activities on the human promyelocytic leukemia cell line, HL-60. Our data show that these compounds induce morphological changes and internucleosomal DNA fragmentation characteristic of apoptotic cell death, which is mediated by caspase-8/caspase-3 activation and cytochrome c release.
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PMID:Isolation from Eucalyptus occidentalis and identification of a new kaempferol derivative that induces apoptosis in human myeloid leukemia cells. 1510 78


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