Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rotenone, an inhibitor of NADH dehydrogenase complex, is a naturally occurring insecticide, which is capable of inducing apoptosis. Rotenone-induced apoptosis is considered to contribute to its anticancer effect and the etiology of Parkinson's disease (PD). We demonstrated that rotenone induced internucleosomal DNA fragmentation, DNA ladder formation, in human cultured cells, HL-60 (promyelocytic leukemia) and BJAB cells (B-cell lymphoma). Flow cytometry showed that rotenone induced H2O2 generation, followed by significant changes in the mitochondrial membrane potential (DeltaPsim). Caspase-3 activity increased in HL-60 cells in a time-dependent manner. These apoptotic events were delayed in HP100 cells, an H2O2-resistant clone of HL-60, confirming the involvement of H2O2 in apoptosis. Expression of anti-apoptotic protein, Bcl-2, in BJAB cells drastically inhibited DeltaPsim change and DNA ladder formation but not H2O2 generation, confirming the participation of mitochondrial dysfunction in apoptosis. NAD(P)H oxidase inhibitors prevented H2O2 generation and DNA ladder formation. These results suggest that rotenone induces O2(-)-derived H2O2 generation through inhibition of NADH dehydrogenase complex and/or activation of NAD(P)H oxidase, and H2O2 generation causes the disruption of mitochondrial membrane in rotenone-induced apoptosis.
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PMID:Mechanism for generation of hydrogen peroxide and change of mitochondrial membrane potential during rotenone-induced apoptosis. 1456 32

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

We have recently found that sodium fluoride (NaF) induced apoptotic cell death in tumor cell lines. We investigated here whether 6 popular antitumor compounds modify the cytotoxic activity of NaF against human squamous cell carcinoma (HSC-2) and human promyelocytic leukemia (HL-60) cell lines. Cytotoxic concentrations of cisplatin, etoposide, doxorubicin or peplomycin (tentatively termed as Group I compounds), but not methotrexate and 5-FU (tentatively termed as Group II compounds), enhanced the cytotoxic activity of NaF. NaF and Group I compounds induced internucleosomal DNA fragmentation in HL-60 cells, whereas Group II compounds were inactive even in the presence of NaF. Most Group I compounds except doxorubicin (which induced DNA fragmentation less effectively than others) activated caspase 3 more efficiently than Group II compounds. Caspase 8 (involved in non-mitochondrial extrinsic pathway) and caspase 9 (involved in mitochondrial intrinsic pathway) were also activated, but to a much lesser extent. NaF reduced the glucose consumption at early stage, possibly by inhibition of glycolysis, whereas cisplatin and etoposide reduced the glucose consumption at later stage, suggesting that early decline of glucose consumption is rather specific to NaF.
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PMID:Effect of antitumor agents on cytotoxicity induction by sodium fluoride. 1498 20

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

A series of simple alpha, beta-unsaturated carbonyl compounds (1-26) was characterized for their cytotoxic profiles against oral human normal and tumor cells. Several cycloalkenones showed potent cytotoxic activities against human oral squamous cell carcinoma HSC-2 cell line. Among them, 4,4-dimethyl-2-cyclopenten-1-one (12) exhibited low cytotoxic activity against a normal human cell, gingival fibroblast HGF, and displayed higher tumor-specific cytotoxicity (SI value = CC50 (HGF)/CC50 (HSC-2) = 4.0). The cytotoxicities of the unsaturated lactones were moderately tumor-specific (SI = 1.5-1.9). Agarose gel electrophoresis showed that the induction of internucleosomal DNA fragmentation in human promyelocytic leukemia cell HL-60 is dependent on the structure of alpha, beta-unsaturated carbonyl compounds. Fluorometric protease assay showed that some, but not all compounds, activated the caspase 3 in a dose-dependent manner. All alpha, beta-unsaturated carbonyl compounds studied did not activate caspases 8 and 9. The cytotoxic activity of alpha, beta-unsaturated carbonyl compounds was profoundly reduced in the presence of N-acetylcysteine. The study suggests that the presence of a non sterically hindered Michael acceptor seems to be an essential structural requirement for the cytotoxic activity in alpha, beta-unsaturated ketones.
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PMID:Structure-activity relationships of alpha, beta-unsaturated ketones as assessed by their cytotoxicity against oral tumor cells. 1516 Oct 20

Hydroxyketone chelators, deferiprone (HK1), maltol (HK3) and their related compounds (HK2, 4-8), were characterized for their cytotoxic profiles against oral human normal and tumor cells. Most hydroxyketones except HK6 showed relatively higher tumor-specific cytotoxicity. Deferiprone (HK1), which showed the highest tumor specificity, had 10 times higher cytotoxicity than maltol (HK3) in both human promyelocytic leukemia HL-60 and human oral squamous cell carcinoma HSC-2 cell lines. The cytotoxic activity of HK1 against HL-60 and HSC-2 cells was reduced in the presence of FeCl3, while that of HK3 was significantly increased by FeCl3. Agarose gel electrophoresis showed that HK1 induced internucleosomal DNA fragmentation in HL-60 cells, but the addition of FeCl3 inhibited the DNA fragmentation. HK3 did not induce DNA fragmentation in HL-60 cells, regardless of the presence or absence of FeCl3. In HSC-2 cells, HK1 and 3 did not induce DNA fragmentation in the presence or absence of FeCl3. Colorimetric protease assay showed that HK1 activated the caspase 3, 8 and 9 in HL-60 cells. On the other hand, HK3 did not activate the caspase 3, 8 and 9 in HL-60 cells, but activated the caspase 3 only slightly in the presence of FeCl3. HK1 and 3 also activated the caspase 3, 8 and 9 in HSC-2 cells, but to a lesser extent. The present study suggested that the antitumor activity of hydroxyketones may be modified by Fe3+ concentration.
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PMID:Cytotoxic activity of deferiprone, maltol and related hydroxyketones against human tumor cell lines. 1516 Oct 23

In this study, we have evaluated the chemopreventive role of aloe-emodin in human promyelocytic leukemia HL-60 cells in vitro by studying the regulation of proliferation, cell cycle and apoptosis. Aloe-emodin inhibited cell proliferation and induced G2/M arrest and apoptosis in HL-60 cells. Investigation of the levels of cyclins B1, E and A by immunoblot analysis showed that cyclin E level was unaffected, whereas cyclin B1 and A levels increased with aloe-emodin in HL-60 cells. Investigation of the levels of cyclin-dependent kinases, Cdk1 and 2, showed increased levels of Cdk1 but the levels of Cdk2 were not effected with aloe-emodin in HL-60 cells. The levels of p27 were increased after HL-60 cells were cotreated with various concentrations of aloe-emodin. The increase of the levels of p27 may be the major factor for aloe-emodin to cause G2/M arrest in these examined cells. Flow cytometric assays and DNA fragmentation gel electrophoresis also confirmed aloe-emodin induced apoptosis in HL-60 cells. The levels of caspase-3 were increased after HL-60 cells were cotreated with 10 microM aloe-emodin for 12, 24, 48, and 72 hours. Taken together, aloe-emodin therefore appears to exert its anticarcinogenesis properties by inhibiting proliferation and inducing cell cycle arrest and apoptosis underwent activation of caspase-3 in human leukemia HL-60 cells.
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PMID:Aloe-emodin induced in vitro G2/M arrest of cell cycle in human promyelocytic leukemia HL-60 cells. 1520 75

Echinocystic acid (EA) is a natural triterpone enriched in various herbs and used for medicinal purpose in many Asian countries. In the present study, we reported that EA can induce apoptosis in human promyelocytic leukemia cells (HL-60), as characterized by DNA fragmentation, poly (ADP) ribose polymerase cleavage. The efficacious induction of apoptosis was observed at 100 microM for 6 h. Further molecular analysis showed that EA induced the cleavage of Bid protein, the loss of mitochondrial membrane potential (DeltaPsim) cytochrome c release from mitochondria into cytosol, and activation of caspase-3, -8 and -9. However, EA did not generate reactive oxygen species (ROS), and antioxidants including N-acetyl cysteine and catalase could not block EA-induced apoptosis in the HL-60 cells. These data suggest that EA induces apoptosis in HL-60 cells through ROS-independent mitochondrial dysfunction pathway.
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PMID:Echinocystic acid induces apoptosis in HL-60 cells through mitochondria-mediated death pathway. 1524 58


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