Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.61 (caspase-8)
 6,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acacetin (5,7-dihydrocy-4'-methoxy flavone), which is a flavonoid compound, possesses anti-peroxidative and anti-inflammatory effects. The effects of acacetin on cell viability in human gastric carcinoma AGS cells were investigated. This study demonstrated that acacetin was able to inhibit cell proliferation and induce apoptosis in a concentration- and time-dependent manner. Acacetin-induced cell death was characterized with changes in nuclear morphology, DNA fragmentation, and cell morphology. The molecular mechanism of acacetin-induced apoptosis was also investigated. Treatment with acacetin caused induction of caspase-3 activity in a time-dependent manner, but not caspase-1 activity, and induced the degradation of DNA fragmentation factor (DFF-45) and poly(ADP-riobse) polymerase. Cell death was completely prevented by a pancaspase inhibitor, Z-Val-Ala-Asp-fluoromethyl ketone. Furthermore, treatment with acacetin caused a rapid loss of mitochondrial transmembrane potential, stimulation of reactive oxygen species (ROS), release of mitochondrial cytochrome c into cytosol, and subsequent induction of procaspase-9 processing. Antioxidants such as N-acetylcysteine and catalase, but not superoxide dismutase, allopurinol, or pyrrolidine dithiocarbamate, significantly inhibited acacetin-induced cell death. In addition, it was found that acacetin promoted the up-regulation of Fas and FasL prior to the processing and activation of pro-caspase-8 and cleavage of Bid, suggesting the involvement of a Fas-mediated pathway in acacetin-induced apoptosis. On the other hand, the results showed that acacetin-induced apoptosis was accompanied by up-regulation of Bax and p53, down-regulation of Bcl-2, and cleavage of Bad. Taken together, these results suggest that ROS production and a certain intimate link might exist between receptor- and mitochondria-mediated death signalings that committed to acacetin-induced apoptosis in AGS cells. The induction of apoptosis by acacetin may provide a pivotal mechanism for its cancer chemopreventive action.
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PMID:Acacetin induces apoptosis in human gastric carcinoma cells accompanied by activation of caspase cascades and production of reactive oxygen species. 1568 11

Flavonoids are naturally occurring antioxidants, with several flavonoids shown to have chemopreventive effects on cancer. We investigated the effects of the flavonoid acacetin on human T cell leukemia Jurkat cells. Acacetin inhibited the proliferation of Jurkat cells by inducing apoptosis in a concentration- and time-dependent manner. Acacetin-induced cell death was characterized by changes in nuclear and cell morphology. Treatment of Jurkat cells with acacetin also induced caspase-3, -8 and -9 activities in a time-dependent manner. Acacetin-induced apoptosis was blocked by a broad-spectrum caspase inhibitor, a caspase-3 inhibitor and a caspase-8 inhibitor, but not by a caspase-9 inhibitor. In addition, acacetin promoted the expression of FAF1, phosphor-FADD, Apaf-1 and cytochrome c. Acacetin-induced apoptosis was also accompanied by upregulation of Bax, and downregulation of Bcl-2. Taken together, these results suggest that acacetin may induce apoptosis in T cell leukemia cells, possibly by activating the Fas-mediated pathway. These findings may help in designing cancer therapeutic and chemopreventive agents.
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PMID:Acacetin induces apoptosis in human T cell leukemia Jurkat cells via activation of a caspase cascade. 2199 65