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)

Near-infrared light via light-emitting diode treatment has documented therapeutic effects on neurons functionally inactivated by tetrodotoxin or methanol intoxication. Light-emitting diode pretreatment also reduced potassium cyanide-induced cell death, but the mode of death via the apoptotic or necrotic pathway was unclear. The current study tested our hypothesis that light-emitting diode rescues neurons from apoptotic cell death. Primary neuronal cultures from postnatal rat visual cortex were pretreated with light-emitting diode for 10 min at a total energy density of 30 J/cm2 before exposing to potassium cyanide for 28 h. With 100 or 300 microM potassium cyanide, neurons died mainly via the apoptotic pathway, as confirmed by electron microscopy, Hoechst 33258, single-stranded DNA, Bax, and active caspase-3. In the presence of caspase inhibitor I, the percentage of apoptotic cells in 300microM potassium cyanide was significantly decreased. Light-emitting diode pretreatment reduced apoptosis from 36% to 17.9% (100 microM potassium cyanide) and from 58.9% to 39.6% (300 microM potassium cyanide), representing a 50.3% and 32.8% reduction, respectively. Light-emitting diode pretreatment significantly decreased the expression of caspase-3 elicited by potassium cyanide. It also reversed the potassium cyanide-induced increased expression of Bax and decreased expression of Bcl-2 to control levels. Moreover, light-emitting diode decreased the intensity of 5-(and -6) chloromethy-2', 7-dichlorodihydrofluorescein diacetate acetyl ester, a marker of reactive oxygen species, in neurons exposed to 300 microM potassium cyanide. These results indicate that light-emitting diode pretreatment partially protects neurons against cyanide-induced caspase-mediated apoptosis, most likely by decreasing reactive oxygen species production, down-regulating pro-apoptotic proteins and activating anti-apoptotic proteins, as well as increasing energy metabolism in neurons as reported previously.
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PMID:Photobiomodulation partially rescues visual cortical neurons from cyanide-induced apoptosis. 1646 35

Smilax has various pharmacological effects including antiinflammatory, anticancer and antioxidant activity. The present study aims to investigate the effect of the methanol extract of Smilacis chinae rhizome (SCR) from Smilax china L. (Liliaceae) on amyloid beta protein (Abeta) (25-35), a synthetic 25-35 amyloid peptide, -induced neurotoxicity in cultured rat cerebral cortical neurons. Abeta (25-35) (10 microM) produced a reduction of cell viability, which was significantly reduced by (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), an N-methyl-D-aspartate (NMDA) receptor antagonist, verapamil, an L-type Ca2+ channel blocker, and NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor. SCR, over a concentration range of 10-50 microg/ml, inhibited 10 microM Abeta (25-35)-induced neuronal cell death, which was measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. SCR (50 microg/ml) inhibited 10 microM Abeta (25-35)-induced elevation of cytosolic calcium concentration ([Ca2+]c), which was measured by a fluorescent dye, Fluo-4 AM. Pretreatment of SCR (10 and 50 microg/ml) also inhibited glutamate release into medium induced by 10 microM Abeta (25-35), which was measured by HPLC, generation of reactive oxygen species and activation of caspase-3. These results suggest that SCR prevents Abeta (25-35)-induced neuronal cell damage in vitro.
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PMID:Protection of amyloid beta protein (25-35)-induced neurotoxicity by methanol extract of Smilacis chinae rhizome in cultured rat cortical neurons. 1649 58

Ganoderma lucidum is a well-known traditional Chinese medicinal herb containing many bioactive compounds. Ganoderic acid T (GA-T), which is a lanostane triterpenoid purified from methanol extract of G. lucidum mycelia, was found to exert cytotoxicity on various human carcinoma cell lines in a dose-dependent manner, while it was less toxic to normal human cell lines. Animal experiments in vivo also showed that GA-T suppressed the growth of human solid tumor in athymic mice. It markedly inhibited the proliferation of a highly metastatic lung cancer cell line (95-D) by apoptosis induction and cell cycle arrest at G(1) phase. Moreover, reduction of mitochondria membrane potential (Delta psi(m)) and release of cytochrome c were observed during the induced apoptosis. Our data further indicate that the expression of proteins p53 and Bax in 95-D cells was increased in a time-dependent manner, whereas the expression of Bcl-2 was not significantly changed; thus the ratio of Bcl-2/Bax was decreased. The results show that the apoptosis induction of GA-T was mediated by mitochondrial dysfunctions. Furthermore, stimulation of the activity of caspase-3 but not caspase-8 was observed during apoptosis. The experiments using inhibitors of caspases (Z-VAD-FMK, Z-DEVD-FMK and Z-IETD-FMK) confirmed that caspase-3 was involved in the apoptosis. All our findings demonstrate that GA-T induced apoptosis of metastatic lung tumor cells through intrinsic pathway related to mitochondrial dysfunction and p53 expression, and it may be a potentially useful chemotherapeutic agent.
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PMID:Ganoderic acid T from Ganoderma lucidum mycelia induces mitochondria mediated apoptosis in lung cancer cells. 1700 87

The new sodium bis(1,2,4-triazol-1-yl)acetate ligand, Na[HC(CO(2))(tz)(2)], has been prepared in methanol solution by using 1,2,4-triazole, dibromoacetic acid, and NaOH. Treatment of the [Cu(CH(3)CN)(4)][PF(6)] acceptor with Na[HC(CO(2))(tz)(2)] or Na[HC(CO(2))[(pz(Me2))(2)] in the presence of the tris(hydroxymethyl)phosphine coligand in methanol/acetonitrile solutions produced unprecedented mononuclear copper(I) complexes of the [L(n)]Cu[P(CH(2)OH)(3)](2) (L(1), 2; L(2), 3) [(CH(3)CN)(2)Cu(P(CH(2)OH)(3))(2)]PF(6), 4. These compounds have been characterized by elemental analyses, FTIR, ESI-MS, and multinuclear (1H and 31P) NMR spectral data. The new copper(I) complexes were tested for their cytotoxic properties against a panel of several human tumor cell lines. The results reported here indicate that all the complexes showed in vitro antitumor activity similar or better than that of cisplatin, the most used metal-based antitumor drug. In particular, [HC(CO(2))(pz(Me2))(2)]Cu[P(CH(2)OH)(3)](2), 3 showed IC(50) values markedly lower than the reference compound against all tumor cell lines. Chemosensitivity tests performed on cisplatin sensitive and resistant cell lines have demonstrated that all these Cu(I) complexes were able to overcome cisplatin resistance, supporting the hypothesis of a different mechanism of action compared to that exhibited by the reference drug. Flow cytometric analysis on 2008 human ovarian carcinoma cells revealed that complex 3, chosen as the best candidate, induced a marked enlargement of both cell size and granularity, and a significant increase in the fraction of G2/M cells that, differently from cisplatin, was not accompanied by the appearance of a relevant sub-G1 fraction. Besides, no evidence of caspase-3 activation was detected in cells treated with complex 3. We hypothesize that the cytotoxic activity of the new copper(I) complex may be correlated to its ability to trigger paraptosis, a nonapoptotic mechanism of cell death.
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PMID:Synthesis, characterization, and in vitro antitumor properties of tris(hydroxymethyl)phosphine copper(I) complexes containing the new bis(1,2,4-triazol-1-yl)acetate ligand. 1714 61

Uncaria tomentosa (Wild.) DC., found in the Amazon rain forest in South-America and known commonly as cat's claw, has been used in traditional medicine to prevent and treat inflammation and cancer. Recently, it has been found to possess potent anti-inflammation activities. In this study, we extracted cat's claw using four different solvents of different polarities and compared their relative influence on proliferation in human premyelocytic leukemia HL-60 cell lines. Cat's claw n-hexane extracts (CC-H), ethyl acetate extracts (CC-EA) and n-butanol extracts (CC-B) had a greater anti-cancer effect on HL-60 cells than those extracted with methanol (CC-M). Furthermore, CC-EA induced DNA fragmentation in HL-60 cells in a clearly more a concentration- and time-dependent manner than the other extracts. CC-EA-induced cell death was characterized by cell body shrinkage and chromatin condensation. Further investigating the molecular mechanism behind CC-EA-induced apoptosis, sells treated with CC-EA underwent a rapid loss of mitochondrial transmembrane (DeltaPsi(m)) potential, stimulation of phosphatidylserine flip-flop, release of mitochondrial cytochrome c into cytosol, induction of caspase-3 activity in a time-dependent manner, and induced the cleavage of DNA fragmentation factor (DFF-45) and PARP poly-(ADP-ribose) polymerase (PARP). CC-EA promoted the up-regulation of Fas before the processing and activation of procaspase-8 and cleavage of Bid. In addition, the apoptosis induced by CC-EA was accompanied by up-regulation of Bax, down-regulation of Bcl-X(L) and cleavage of Mcl-1, suggesting that CC-EA may have some compounds that have anti-cancer activities and that further studies using cat's claw extracts need to be pursued. Taken together, the results of our studies show clearly that CC-EA's induction of apoptosis in HL-60 cells may make it very important in the development of medicine that can trigger chemopreventive actions in the body.
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PMID:Induction of apoptosis by Uncaria tomentosa through reactive oxygen species production, cytochrome c release, and caspases activation in human leukemia cells. 1761 71

The present study is part of a large-scale investigation of the antitumor effects of Biophytum sensitivum on B16F-10 melanoma cells. The investigation involved the regulatory effect of B sensitivum on nitric oxide and cytokine production in B16F-10 cells, tumor-associated macrophages, and peritoneal macrophages as well as on the apoptotic process in B16F-10 melanoma cells. B sensitivum at a concentration of 10 microg/mL could significantly (P< .001) inhibit production of nitric oxide and proinflammatory cytokines such as interleukin-1beta, interleukin-6, granulocyte monocyte-colony stimulating factor, and tumor necrosis factor-alpha in B16F-10 cells, tumor-associated macrophages, and peritoneal macrophages. Incubation of B16F-10 cells with B sensitivum showed the presence of apoptotic bodies and induced DNA fragmentation. Furthermore, B sensitivum showed an inhibitory effect on inducible nitric oxide synthase as well as bcl-2 expression, and up-regulated p53 and caspase-3 messenger RNA expression in B16F-10 melanoma cells. The observed results suggest that regulation of proinflammatory cytokine production by tumor cells, tumor-associated macrophages, and resident macrophages accompanied by altered inducible nitric oxide synthase, bcl-2, caspase-3, and p53 messenger RNA expression by B sensitivum methanol extract induces apoptosis in B16F-10 melanoma cells.
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PMID:Apoptotic effect of Biophytum sensitivum on B16F-10 cells and its regulatory effects on nitric oxide and cytokine production on tumor-associated macrophages. 1804 85

Phellodendri Cortex (PC) is a traditional herbal medicine, widely used in Korea and China. The effects of the methanol extract of Phellodendri Cortex (PC extract) on 1-methyl-4-phenylpyridinium (MPP(+))-induced neuronal apoptosis in PC-12 cells have been investigated. MPP(+)-induced apoptosis in PC-12 cells was accompanied by an increased bax/bcl-2 ratio, release of cytochrome c to the cytosol and activation of caspase-3. PC extract inhibited the downregulation of bcl-2 and the upregulation of bax, as well as the release of mitochondrial cytochrome c into the cytosol. In addition, PC extract attenuated caspase-3 activation and cleavage of poly (ADP-ribose) polymerase (PARP). These results suggest that the PC extract has protective effects against MPP(+)-induced neuronal apoptosis in PC-12 cells.
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PMID:Neuroprotective effect of methanol extract of Phellodendri Cortex against 1-methyl-4-phenylpyridinium (MPP+)-induced apoptosis in PC-12 cells. 1952 85

Three known (1-3) and a novel (4) monoterpene indole alkaloids have been isolated from the methanol extract of leaves of Tabernaemontana elegans and their structures were elucidated by a series of spectroscopic experiments, involving NMR, MS, UV, and IR techniques. The isolated monoterpene indole alkaloids along with previously described beta-carbolines (5-7) from the same specimen were studied for their apoptosis induction activity in human hepatoma HuH-7 cells. Methodology for apoptosis induction studies included cell viability assays, nuclear morphology assessments, and general caspase-3-like activity assays. The monoterpene indole alkaloids, tabernaemontanine (1) and vobasine (3) showed the most promising apoptosis induction profile in HuH-7 cells.
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PMID:Induction of apoptosis in HuH-7 cancer cells by monoterpene and beta-carboline indole alkaloids isolated from the leaves of Tabernaemontana elegans. 1952 11

Medullary thyroid carcinoma (MTC), a neuroendocrine tumor arising from the thyroid gland, is known to be poorly responsive to conventional chemotherapy. The root of Stemona tuberosa Lour, also called Bai Bu, is a commonly used traditional Chinese anti-tussive medicine. The present study investigated this medicinal herb for the first time with respect to its anticancer activity in human medullary thyroid carcinoma cells. Four extracts of Stemona tuberosa Lour, including the n-hexane fraction, (ST-1), dichloromethane (DCM) fraction, (ST-2), ethyl acetate (EtOAc) fraction, (ST-3), and methanol fraction, (ST-4) were examined for antiproliferative effects in two MTC cell lines. We observed that only the DCM fraction ST-2 inhibited cell growth and viability in a dose-dependent manner. Furthermore, we found that ST-2 also induced the apoptosis of MTC-SK cells. Caspase-3/7 was activated, while caspase-9 was not, implying that at least a caspase-dependent apoptotic pathway was involved in this process. In addition, the multicellular spheroids of MTC-SK were destroyed and the cell morphology was changed by ST-2. Our results show the strong apoptotic effects of the DCM fraction of Stemona tuberosa Lour on human medullary thyroid carcinomas, so suggesting a new candidate for chemotherapy of the so far chemo-resistant medullary thyroid carcinoma.
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PMID:The dichloromethane fraction of Stemona tuberosa Lour inhibits tumor cell growth and induces apoptosis of human medullary thyroid carcinoma cells. 1970 15

Hypericum perforatum (St. John's wort) is well-established for its antidepressant activity throughout the world and also various other species within this genus are used in different folk medicines. Hyperforin of St. John's wort inhibited growth of cancer cell lines and the use of hypericin (another compound of H. perforatum) in cancer photodynamic therapy is proposed. Therefore, we investigated the anti-cancer properties of H. adenotrichum Spach (Guttiferae), an endemic species in Turkey called 'kantaron', which is used for wound healing and antiseptic effects. Freeze-dried plant was extracted with petroleum ether, dichloromethane, ethyl acetate, and methanol and the bioactivity of these extracts was analysed by proliferation assay, cell death determination, by investigating protein expression profiles specific for cell cycle arrest and apoptosis as well as composition by HPLC. The strongest anti-proliferative activity was determined for the petroleum ether extract with an IpC50 of approximately 5.8 microg/ml medium (referring to 1 mg dried plant) which correlated with cyclin D1 suppression and p21 induction. This extract also induced phosphorylation of H2AX, and activated caspase-3 followed by signature-type cleavage of PARP resulting in approximately 50% apoptosis at 23.2 microg/ml after 24 h of treatment. Neither hyperforin, hypericin, or amentoflavone contributed to these properties. To the best of our knowledge, we report for the first time that the endemic plant H. adenotrichum Spach exhibits potent p53-independent anti-neoplastic properties due to yet unexplored Hypericum constituents.
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PMID:In vitro anti-neoplastic activity of the ethno-pharmaceutical plant Hypericum adenotrichum Spach endemic to Western Turkey. 1972 64


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