Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.62 (caspase-9)
 7,507 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was performed to elucidate the apoptotic pathways by thiosulfinates, major biologically active components of Allium tuberosum L., in HT-29 human colon cancer cells. Thiosulfinates significantly induced cell death in dose- and time-dependent manners in HT-29 cells, which is associated with apoptosis. Thiosulfinates activated the initiator caspase-8, and -9, and the effector caspase-3. In the present study, thiosulfinates were found to stimulate Bid cleavage, indicating that the apoptotic action of caspase-8-mediated Bid cleavage leads to the activation of caspase-9. Thiosulfinates down-regulated the expression of the anti-apoptotic protein Bcl-2, and up-regulated the expression of the pro-apoptotic protein Bax. We also found that thiosulfinates increased the expression of AIF, a caspase-independent mitochondrial apoptosis factor, and induced DNA fragmentation and chromatin condensation in HT-29 cells. These results indicate that thiosulfinates from A. tuberosum L. inhibited cell proliferation and activated both the caspase-dependent and caspase-independent apoptotic pathways in HT-29 cells.
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PMID:Mechanisms of thiosulfinates from Allium tuberosum L.-induced apoptosis in HT-29 human colon cancer cells. 1944 47

This study was performed to elucidate the anti-proliferative effects and the apoptotic mechanisms of extracts from Lethariella zahlbruckneri in HT-29 human colon cancer cells. Both the acetone extract (AEL) and methanolic extract (MEL) of L. zahlbruckneri decreased viable cell numbers in a dose- and time-dependent manner in HT-29 cells. The AEL showed stronger cytotoxicity than MEL. Cell death induced by AEL increased cell populations in the sub-G1 phase, as well as the formation of apoptotic bodies and nuclear condensation, whereas MEL did not. Therefore, the potential of AEL to induce apoptosis was examined. Apoptosis induced by AEL was associated with the activation of initiator caspases-8 and -9, as well as the effector caspase-3. AEL stimulated Bid cleavage. This indicated that the apoptotic action of caspase-8-mediated Bid cleavage leads to the activation of caspase-9. AEL increased the expression of the pro-apoptotic protein, Bax, and decreased the expression of the anti-apoptotic protein, Bcl-2. AEL also increased the expression of the caspase-independent mitochondrial apoptosis factor, AIF, in HT-29 cells. These results indicate that AEL inhibited HT-29 cell proliferation by inducing apoptosis, which might be mediated via both caspase-dependent and -independent pathways.
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PMID:Anti-proliferative effects of Lethariella zahlbruckneri extracts in human HT-29 human colon cancer cells. 1950 Nov 27

Elastin peptides regulate proliferation, chemotaxis and protease expression. The aim of this work was to assess their influence on apoptosis. Human skin fibroblast cell death was induced using C(2)-ceramide in the presence or absence of elastin peptides. We show that ceramide-induced apoptosis could be blocked by elastin peptides. Using pharmacological inhibitors, we show that elastin peptide treatment leads to activation of the anti-apoptotic protein Akt that phosphorylates the pro-apoptotic protein Bad, the Foxo3a transcription factor and caspase-9. Importantly, the anti-apoptotic effects of elastin peptides were persistent in time. Our results suggest that elastin peptides could be potent cell survival factors.
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PMID:Elastin peptides antagonize ceramide-induced apoptosis. 1955 25

Lanthanides have been reported to induce apoptosis in cancer cell lines. Human cervical cancer cell line HeLa was found to be more sensitive to dicitratolanthanum (III) complex ([LaCit2](3-)) than other cancer cell lines. However, the effect and mechanism of dicitratoytterbium (III) complex ([YbCit2](3-)) on HeLa cells is unknown. Using biochemical and comparative proteomic analyses, [YbCit2](3-) was found to inhibit HeLa cell growth and induce apoptosis. Similar to the effects of [LaCit2](3-), proteomics results from [YbCit2](3-)-treated cells revealed profound changes in proteins relating to mitochondria and oxidative stress, suggesting that mitochondrial dysfunction plays a key role in [YbCit2](3-)-induced apoptosis. This was confirmed by the decreased mitochondrial transmembrane potential and the increased generation of reactive oxygen species in [YbCit2](3-)-treated cells. Western blot analysis showed that [YbCit2](3-)-induced apoptosis was accompanied by the activation of caspase-9 and specific proteolytic cleavage of PARP, leading to an increase in the pro-apoptotic protein Bax and a decrease in the anti-apoptotic protein Bcl-2. These results suggest a mitochondrial pathway of cell apoptosis in [YbCit2](3-)-treated cells, which will help us understand the molecular mechanisms of lanthanide-induced apoptosis in tumor cells.
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PMID:A proteomic investigation into the human cervical cancer cell line HeLa treated with dicitratoytterbium (III) complex. 1963 12

In the present study, we investigated the neuroprotective effects of schisandrin B on amyloid-beta1-42-induced toxicity and its potential mechanisms in rat cortical neuron cells. Amyloid beta1-42 significantly reduced cell viability and increased apoptosis. Pretreatment with schisandrin B prior to amyloid-beta1-42 exposure significantly elevated cell viability and reduced apoptosis. The anti-apoptotic effect of schisandrin B in rat cortical neurons was mediated by up-regulation of the anti-apoptotic protein Bcl-2 and down-regulation of the pro-apoptotic protein Bax. Schisandrin B also reduced the release of mitochondrial cytochrome c into cytosol and decreased caspase-9 and caspase-3 activities. Furthermore, schisandrin B increased activities of anti-oxidant reduced glutathione and decreased production of oxidative glutathione. Taken together, these results suggest that schisandrin B protected primary cultures of rat cortical cells against amyloid-beta1-42-induced neurotoxicity through anti-apoptosis involved in a mitochondria-mediated pathway and anti-oxidant action. Schisandrin B may represent a potential treatment strategy for Alzheimer's disease.
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PMID:Schisandrin B protects rat cortical neurons against Abeta1-42-induced neurotoxicity. 1969 82

It is well known that Phellinus linteus has a variety of biological functions, such as antitumor and immunomodulating activities. In our previous studies, we developed a P. linteus grown on germinated brown rice (PBR) and found that organic solvent extracts of PBR possessed immunomodulating activity to regulate a balance of cytokine network in mice. The components of PBR are ergosterol peroxide, gamma-aminobutyric acid (GABA) and Beta-glucan. In this study, we demonstrate that an organic solvent extract of P. linteus grown on PBR induced apoptotic cell death through the induction of G(0)/G(1) arrest of cell cycle and the apoptosis via DNA fragmentation in human colon carcinoma HT-29 cells. Cell death induced by the extract of P. linteus grown on PBR was shown to be associated with the upregulation of p21(CIP1/WAF1), the downregulation of cyclin D1, anti-apoptotic protein, Bcl-2, the release of cytochrome c, and the activation of caspase-9, caspase-3 and caspase-8. This study suggests that the ethyl acetate extract of P. linteus grown on PBR induces apoptosis accompanied by cell cycle arrest at G(0)/G(1) phase and regulates apoptosis-regulatory proteins, which may be applicable to anticancer therapy.
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PMID:The ethyl acetate extract of Phellinus linteus grown on germinated brown rice induces G0/G1 cell cycle arrest and apoptosis in human colon carcinoma HT29 cells. 1999 18

The small heat shock protein Hsp27 is a molecular chaperone and an anti-apoptotic protein. Human Hsp27 has one cysteine residue at position 137. We investigated the role of this cysteine residue in the chaperone and anti-apoptotic functions of Hsp27 by mutating the cysteine residue to an alanine (Hsp27(C137A)) and comparing it to wild-type protein (Hsp27(WT)). Both proteins were multi-subunit oligomers, but subunits of Hsp27(WT) were disulfide-linked unlike those of Hsp27(C137A), which were monomeric. Hsp27(C137A) was indistinguishable from Hsp27(WT) with regard to its secondary structure, surface hydrophobicity, oligomeric size and chaperone function. S-thiolation and reductive methylation of the cysteine residue had no apparent effect on the chaperone function of Hsp27(WT). The anti-apoptotic function of Hsp27(C137A) and Hsp27(WT) was studied by overexpressing them in CHO cells. No difference in the caspase-3 or -9 activity was observed in staurosporine-treated cells. The rate of apoptosis between Hsp27(C137A) and Hsp27(WT) overexpressing cells was similar whether the cells were treated with staurosporine or etoposide. However, the mutant protein was less protective relative to the wild-type protein in preventing caspase-3 and caspase-9 activation and apoptosis induced by 1 mM H(2)O(2) in CHO and HeLa cells. These data demonstrate that in human Hsp27, disulfide formation by the lone cysteine does not affect its chaperone function and anti-apoptotic function against chemical toxicants. However, oxidation of the lone cysteine in Hsp27 might at least partially affect the anti-apoptotic function against oxidative stress.
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PMID:The role of the cysteine residue in the chaperone and anti-apoptotic functions of human Hsp27. 2022 72

Butyrate has been shown to display anti-cancer activity through the induction of apoptosis in various cancer cells. However, the underlying mechanism involved in butyrate-induced apoptosis is still not fully understood. Here, we investigated the cytotoxicity mechanism of butyrate in human colon cancer RKO cells. The results showed that butyrate induced a strong growth inhibitory effect against RKO cells. Butyrate also effectively induced apoptosis in RKO cells, which was characterized by DNA fragmentation, nuclear staining of DAPI, and the activation of caspase-9 and caspase-3. The expression of anti-apoptotic protein Bcl-2 decreased, whereas the apoptotic protein Bax increased in a dose-dependent manner during butyrate-induced apoptosis. Moreover, treatment of RKO cells with butyrate induced a sustained activation of the phosphorylation of c-jun N-terminal kinase (JNK) in a dose- and time-dependent manner, and the pharmacological inhibition of JNK MAPK by SP600125 significantly abolished the butyrate-induced apoptosis in RKO cells. These results suggest that butyrate acts on RKO cells via the JNK but not the p38 pathway. Butyrate triggered the caspase apoptotic pathway, indicated by an enhanced Bax-to-Bcl-2 expression ratio and caspase cascade reaction, which was blocked by SP600125. Taken together, our data indicate that butyrate induces apoptosis through JNK MAPK activation in colon cancer RKO cells.
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PMID:Butyrate induces cell apoptosis through activation of JNK MAP kinase pathway in human colon cancer RKO cells. 2034 29

orf390 (WSSV449) is a novel apoptosis inhibitor gene in the genome of the White Spot Syndrome Virus (WSSV). In the present study, we focus on the function of orf390 gene. Stable expression of orf390 prevented SF9 insect cells from undergoing actinomycin D-induced apoptosis. ORF390 also rescued the replication of a p35-deficient-mutant (AcMNPVDeltap35k/pol+) in SF9 cells. In addition, ORF390 inhibits the activities of caspase-3 and -9 in vivo and in vitro. Here we demonstrate that the anti-apoptotic activity of ORF390 is dependent on two putative caspase-9 cleavage sites (VETD233 downward arrowG and LEHD303 downward arrowG) and one caspase-3 cleavage site (DEVD272 downward arrowG). Our results support the conclusion that these three sites play a key role in the suppression of apoptosis mediated by ORF390. These data further suggest that orf390 encodes a novel anti-apoptotic protein involved in cell survival and apoptosis regulation.
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PMID:Functional analysis of the orf390 gene of the white spot syndrome virus. 2036 18

Both Notch signaling and Akt-mTOR signaling pathway are involved in glioma cell proliferation and survival. Previous studies have shown that Notch-1 is overexpressed in many glioma cell lines and primary human gliomas. Blocking of Notch signaling pathway can induces glioma cell apoptosis and growth suppression. However, the underlying molecular mechanism is not clear. We report that activation of the Notch pathway by intracellular domain of human Notch-1 (NIC-1) strongly activates Akt and promotes U251 glioma cell proliferation. Knockdown of Notch-1 by RNA interference suppresses Akt activation, reduces glioma cell growth rate and induce cell apoptosis. Following Notch-1 suppression, phosphorylated Akt and its downstream effector mTOR were reduced. Knockdown of Notch-1 also involves down-regulation of anti-apoptotic protein MCL-1, in parallel with activation of apoptotic associate proteins PARP, caspase-9 and caspase-3. Our data demonstrate that Notch-1 can positively regulate Akt-mTOR pathways, which is associated with glioma cell proliferation and apoptosis. This also suggests a molecular mechanism for the inhibitory effect of Notch-1 RNA interference on glioma cell proliferation through Akt-mTOR signaling pathway.
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PMID:Akt-mTOR signaling is involved in Notch-1-mediated glioma cell survival and proliferation. 2037 62


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