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: UNIPROT:P42574 (caspase-3)
45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A total of thirty-nine naphtho[2,3-b]furan-4,9-diones and related compounds were tested for their cytotoxicity against three human normal oral cells (gingival fibroblast, HGF, pulp cell, HPC, periodontal ligament fibroblast, HPLF) and four human tumor cell lines (oral squamous cell carcinoma HSC-2, HSC-3, HSC-4, promyelocytic leukemia HL-60). 2-Acetylnaphtho[2,3-b]furan-4,9-dione [1] was highly cytotoxic to both normal and tumor cells, yielding low tumor-specificity. 2-Acetyl-4,9-dimethoxynaphtho[2,3-b]furan [4], the 2-(3-furanoyl) benzoic acids [5, 6] and the 1,4-naphthoquinones [7, 8] showed much reduced cytototoxicity and low tumor-specificity. The introduction of phenoxy [18], isopropylamino [23] or 2-methylpiperidino [33] groups to the 2-position of naphtho[2,3-b]furan-4,9-dione yielded compounds that showed the greatest tumor-specificity. These compounds, at twice or four times higher concentrations than CC50, induced the activation of caspase-3, caspase-8 and caspase-9 in the HSC-2 and HL-60 cells, but not so apparently in the HSC-4 cells. However, they did not induce internucleosomal DNA fragmentation in the HSC-2 and HSC-4 cells even after 24 hours incubation and only slightly induced DNA fragmentation in the HL-60 cells. Compound [18] induced the production of annexin-positive cells, but did not induce microtubule-associated protein light chain 3 (LC3) accumulation in autophagosomes in LC3-green fluorescent protein (GFP)-transfected HSC-2 cells. These data suggested that naphtho[2,3-b]furan-4,9-diones may induce the early apoptotic marker, without induction of caspase activation and DNA fragmentation in oral squamous cell carcinoma cell lines. Quantitative structure-activity relationship (QSAR) analysis suggests the applicability of the theoretical calculations such as frontier molecular orbital, dipole moments and hydrophobicity in predicting their cytotoxic activity.
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PMID:Tumor-specific cytotoxicity and type of cell death induced by naphtho[2,3-b]furan-4,9-diones and related compounds in human tumor cell lines: relationship to electronic structure. 1933 Nov 86

A total of twenty benzo[b]cyclohept[e] [1,4]oxazines and their S-analogs, and 2-aminotropone derivatives were investigated for their cytotoxicity against three human normal cells and four tumor cell lines. These compounds showed moderate tumor-specific cytotoxicity. The cytotoxicity was enhanced by bromination at the tropone ring and replacement by formylbenzene. The cytotoxicity of 2-(2-hydroxyanilino) tropone was enhanced by introduction of bromine or isopropyl group to the tropone ring. The presence of a hydroxyl group at ortho or para-position should be necessary for the appearance of cytotoxicity and tumor-specificity. The highly active derivatives, 7-bromo-2-(4-hydroxyanilino)tropone [16] and 4-isopropyl-2-(2-hydroxyanilino)tropone [20], induced internucleosomal DNA fragmentation and caspase-3, -8 and -9 activation in human promyelocytic leukemia HL-60 cells, but only at concentrations twice or four times higher than CC(50) values. These compounds induced no discernible DNA fragmentation, and activated caspases much more weakly in human oral squamous cell carcinoma HSC-2 cells. Both [16] and [20] failed to induce the production of acidic organelles, a marker of autophagy, in contrast to the nutritional starvation. These data demonstrated that 2-aminotropones showed relatively higher tumor-specificity than benzo[b]cyclohept[e] [1,4]oxazine, and that 2-aminotropones induced little or no apoptotic cell death in oral squamous cell carcinoma, in contrast to HL-60 cells.
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PMID:Tumor-specific cytotoxicity and type of cell death induced by benzo[b]cyclohept[e][1,4]oxazine and 2-aminotropone derivatives. 1941 54

Mastic is a resinous exudate obtained from the stem and the main leaves of Pistacia lentiscus. We have reported the antiplaque effect of mastic-containing chewing gum on the oral cavity. We hypothesize that mastic may be a multifunctional food which has some beneficial pharmaceutical properties. The aim of this study was to assess the biological activity of solid and liquid types of mastic by cytotoxicity against fibroblasts, radical-scavenging activities and inhibitory effect on cell death of oral polymorphonuclear leukocytes (OPMNs). Mastic showed selective antibacterial action against Porphyromonas gingivalis and Prevotella melaninogenica, but no anti-HIV activity. Among a total of thirteen human cell types, promyelocytic leukemia HL-60 was the most sensitive to the cytotoxicity of mastic, followed by myeloblastic leukemia (ML-1, KG-1), erythroleukemia (K-562), oral squamous cell carcinoma (HSC-2, HSC-3, HSC-4), hepatocellular carcinoma (HepG2), glioblastoma (T98G, U87MG) and normal oral cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast, most resistant). Mastic did not induce the differentiation of myelogenous leukemic cells into maturing cells with higher nitroblue tetrazolium-reducing activity, but induced apoptotic cell death, characterized by internucleosomal DNA fragmentation, caspase-3 activation and a decline in the intracellular concentration of putrescine. The cytotoxicity of mastic against leukemic cells did not diminish during its storage. On the other hand, mastic inhibited the spontaneous apoptosis of OPMNs. Mastic showed hydroxyl radical-scavenging activity. The selective antibacterial and apoptosis-modulating activity of mastic suggests its possible beneficial effects on oral health.
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PMID:Selective antibacterial and apoptosis-modulating activities of mastic. 1941 6

Terminalia calamansanai (Blanco) Rolf. (Combretaceae) is used medicinally as lithontriptic in Philippines. The 70% acetone extracts of T. calamansanai leaves inhibited the viability of human promyelocytic leukemia HL-60 cells. 1-Alpha-O-galloylpunicalagin, punicalagin, 2-O-galloylpunicalin, sanguiin H-4, and methyl gallate were the main components isolated from T. calamansanai with the IC(50) values of 65.2, 74.8, 42.2, 38.0 and >100 microM, respectively, for HL-60 cells. Apoptosis of HL-60 cells treated with 1-Alpha-O-galloylpunicalagin, punicalagin, 2-O-galloylpunicalin, and sanguiin H-4 was noted by the appearance of a sub-G(1) peak in flow cytometric analysis and DNA fragmentation by gel electrophoresis. 2-O-Galloylpunicalin and sanguiin H-4 induced a decrease of the human poly(ADP-ribose)polymerase (PARP) cleavage-related procaspase-3 and elevated activity of caspase-3 in HL-60 cells, but not normal human peripheral blood mononuclear cells (PBMCs), suggesting that both compounds may be new candidates for drug development in the prevention and treatment of cancer.
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PMID:Ellagitannins from Terminalia calamansanai induced apoptosis in HL-60 cells. 1949 Aug 39

Eight new spirostanol saponins (1-8) and three new furostanol saponins (9-11) were isolated from the whole plants of Agave utahensis. The structures of 1-11 were determined by analysis of extensive spectroscopic data. The saponins were evaluated for their cytotoxic activity against HL-60 human promyelocytic leukemia cells. Compound 1 showed cytotoxicity against HL-60 cells with an IC(50) value of 4.9 microg/mL, induced apoptosis in HL-60 cells, and markedly activated caspase-3.
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PMID:Steroidal glycosides from Agave utahensis and their cytotoxic activity. 1964 63

Selenium is an essential chemopreventive antioxidant element to oxidative stress, although high concentrations of selenium induce toxic and oxidative effects on the human body. However, the mechanisms behind these effects remain elusive. We investigated toxic effects of different selenium concentrations in human promyelocytic leukemia HL-60 cells by evaluating Ca(2+) mobilization, cell viability and caspase-3 and -9 activities at different sample times. We found the toxic concentration and toxic time of H(2)O(2) as 100 microM: and 10 h on cell viability in the cells using four different concentrations of H(2)O(2) (1 microM: -1 mM: ) and six different incubation times (30 min, 1, 2, 5, 10, 24 h). Then, we found the therapeutic concentration of selenium to be 200 nM: by cells incubated in eight different concentrations of selenium (10 nM: -1 mM: ) for 1 h. We measured Ca(2+) release, cell viability and caspase-3 and -9 activities in cells incubated with high and low selenium concentrations at 30 min and 1, 2, 5, 10 and 24 h. Selenium (200 nM: ) elicited mild endoplasmic reticulum stress and mediated cell survival by modulating Ca(2+) release, the caspases and cell apoptosis, whereas selenium concentrations as high as 1 mM: induced severe endoplasmic reticulum stress and caused cell death by activating modulating Ca(2+) release, the caspases and cell apoptosis. In conclusion, these results explained the molecular mechanisms of the chemoprotective effect of different concentrations of selenium on oxidative stress-induced apoptosis.
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PMID:Selenium modulates oxidative stress-induced cell apoptosis in human myeloid HL-60 cells through regulation of calcium release and caspase-3 and -9 activities. 1989 92

We compared the pro-apoptotic effect of two dibenzocyclooctadiene lignans, gomisin A and gomisin N, isolated from Schizandra chinensis Baill, in U937 human promyelocytic leukemia cells in vitro. Gomisin N, but not gomisin A, inhibited cell growth in a dose-dependent manner, which was associated with the induction of apoptosis. The increase in apoptosis that was induced by gomisin N was correlated with down-regulation of anti-apoptotic Bcl-2 expression, a decrease in the mitochondrial membrane potential (MMP) and a release of cytochrome c from the mitochondria into the cytosol. Furthermore, gomisin N induced the proteolytic activation of caspase-9 and -3 and a concomitant degradation of poly(ADP-ribose) polymerase. However, caspase-8 was not activated and cleavage of Bid was not observed in gomisin N-treated U937 cells. The cytotoxic effects and apoptotic characteristics induced by gomisin N were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, demonstrating the important role that caspase-3 plays in the process. We conclude that gomisin N induces the apoptosis of U937 cells through a signaling cascade of mitochondria-mediated intrinsic caspase pathways and gomisin N may be a useful chemotherapeutic agent.
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PMID:Apoptosis induction of human leukemia U937 cells by gomisin N, a dibenzocyclooctadiene lignan, isolated from Schizandra chinensis Baill. 2003 37

Gefitinib is an orally active, selective epidermal growth factor receptor-tyrosine kinase inhibitor. The present study was aimed at evaluating the antitumor activity of gefitinib alone or in combination with other antitumor agents. Gefitinib showed higher cytotoxicity against five human tumor cell lines (HSC-2, HSC-3, HSC-4, T98G and U87MG) than against three human normal oral cells (gingival fibroblast HGF, pulp cell HPC and periodontal ligament fibroblast HPLF). Gefitinib showed little or no growth stimulation effects at lower concentrations (so-called hormetic effect). Non-cytotoxic concentration of gefitinib effectively enhanced the cytotoxicity of docetaxel against HSC-2 and T98G cell, but failed to enhance the cytotoxicity of other antitumor agents (mitoxantrone, doxorubicin, methotrexate, cisplatin, sodium ascorbate, sodium fluoride) or herbal extracts (Drynaria baronii, Angelica sinensis and Cornus officinalis Sieb. et Zucc). Gefitinib alone and combined with docetaxel induced internucleosomal DNA fragmentation and caspase-3 activation in human promyelocytic leukemia HL-60 cells, but not in HSC-2 or T98G cells. Combination treatment with gefitinib and docetaxel induced the formation of acidic organelles (stained with acridine orange) and mitochondrial shrinkage, vacuolization and production of autophagosome and the loss of cell surface microvilli, without destruction of cell surface and nuclear membranes in HSC-2 and T98G cells (demonstrated by transmission electron microscopy), suggesting the induction of autophagy in HSC-2 and T98G cells.
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PMID:Tumor-specific cytotoxicity and type of cell death induced by gefitinib in oral squamous cell carcinoma cell lines. 2004 12

Protein phosphatase 2C (PP2C) dephosphorylates a broad range of substrates and regulates apoptosis, stress response and growth-related pathways. In the course of screening for PP2C activators from natural sources, we isolated abietane-type diterpenes, pisiferdiol and pisiferic acid from Chamaecyparis pisifera. Pisiferdiol having a unique seven-membered ring showed more specific PP2C activation activity (1.3-fold at 100 microM) than pisiferic acid having a normal six-membered ring and oleic acid, which is known to activate PP2C. Pisiferdiol and pisiferic acid showed mixed-type activation with respect to alpha-casein, and this differed from the non-competitive activation of oleic acid in vitro. In vivo, the cytotoxicity of pisiferdiol toward human promyelocytic leukemia cell line HL60 with an IC(50) value of 18.3 microM was 2-fold and 7-fold stronger than those of pisiferic acid and oleic acid, and pisiferdiol induced apoptosis through a caspase 3/7-dependent mechanism involving the dephosphorylation of Bad(1), which is a PP2C substrate. We thus conclude that pisiferdiol and pisiferic acid are novel PP2C activators, and the more specific activator, pisiferdiol, may be a useful chemical probe to study PP2C-mediated signaling pathways, and a lead compound for pharmaceutical agents.
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PMID:Pisiferdiol and pisiferic acid isolated from Chamaecyparis pisifera activate protein phosphatase 2C in vitro and induce caspase-3/7-dependent apoptosis via dephosphorylation of Bad in HL60 cells. 2015 20

Sanguinarine, a plant alkaloid, was identified as a potent and specific protein phosphatase (PP) 2C inhibitor. It inhibited PP2C competitively with respect to alpha-casein (Ki=0.68 microM) and showed selectivity for PP2C as compared with PP1, PP2A, and PP2B in vitro. In vivo, sanguinarine showed cytotoxicity toward human promyelocytic leukemia cell line HL60, with an IC(50) value of 0.37 microM, and induced apoptosis through a caspase-3/7-dependent mechanism involving the phosphorylation of p38, a PP2Calpha substrate. The apoptosis activity induced by sanguinarine was partially inhibited by a p38 inhibitor, SB203580, and was involved in the phospho-p38 protein in HL60 cells.
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PMID:Sanguinarine as a potent and specific inhibitor of protein phosphatase 2C in vitro and induces apoptosis via phosphorylation of p38 in HL60 cells. 2020 61


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