Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.56 (caspase-3)
 35,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Caspase-3 was activated in apoptotic L-MAT cells by treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Treatment with tributyltin, which has been reported to induce apoptosis in rat thymocytes, also activated caspase-3 and led to cell death in L-MAT cells. Blocking caspase-3 activity with the peptide inhibitor, DEVE-CHO, prevented TCDD from inducing subsequent apoptotic changes. The potent Ah receptor ligand, 2,3,7,8-tetrachlorodibenzofuran (TCDF), the low acute toxicity compound, 1,2,3,4,6,7,9-heptachlorodibenzo-p-dioxin (HCDD), and one of the major contaminants in human milk, 3,3',4,4',5-pentachlorobiphenyl (PCBP), increased the activation level of caspase-3, each in a dose-dependent manner. Thus, we propose that measuring caspase-3 activation in the human T-lymphoblastic cell line, L-MAT, is a useful evaluation method for the immunotoxicity of dioxin compounds.
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PMID:Method for evaluation of immunotoxicity of dioxin compounds using human T-lymphoblastic cell line, L-MAT. 1137 70

Isoliquiritigenin (ISL), a simple chalcone derivative, 4,2',4'-trihydroxychalcone, found in licorice, shallot and bean sprouts, has been reported to have chemoprotective effects. To examine the effects of ISL on the growth of prostate cancer cells, we cultured MAT-LyLu (MLL) rat and DU145 human prostate cancer cells with various concentrations (0-20 micromol/L) of ISL. Treatment of the cells with increasing concentrations of ISL led to dose-dependent decreases in the viable cell numbers in both DU145 and MLL cells (P<.05). Hoechst 33258 dye staining of condensed nuclei and annexin V binding to surface phosphatidylserine revealed increased numbers of apoptotic cells after ISL treatment. Western blot analysis revealed that ISL increased the levels of membrane-bound Fas ligand (FasL), Fas, cleaved casapse-8, truncated Bid (tBid), Bax and Bad in DU145 cells (P<.05). Isoliquiritigenin increased the percentage of cells with depolarized mitochondrial membranes, in a concentration-dependent manner (P<.05). Isoliquiritigenin induced the release of cytochrome c and Smac/Diablo from the mitochondria into the cytoplasm (P<.05). Isoliquiritigenin dose-dependently increased the levels of cleaved caspase-9, caspase-7, caspase-3 and poly(ADP-ribose) polymerase (P<.05). The present results indicate that ISL inhibits prostate cancer cell growth by the induction of apoptosis, which is mediated through mitochondrial events, which are associated with an evident disruption of the mitochondrial membrane potential, and the release of cytochrome c and Smac/Diablo, and the activation of caspase-9.
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PMID:Isoliquiritigenin induces apoptosis by depolarizing mitochondrial membranes in prostate cancer cells. 1651 40

Methionine adenosyltransferase II (MAT II) is a key enzyme in cellular metabolism and catalyzes the formation of S-adenosylmethionine (SAMe) from L-methionine and ATP. Normal resting T lymphocytes have minimal MAT II activity, whereas activated proliferating T lymphocytes and transformed T leukemic cells show significantly enhanced MAT II activity. This work was carried out to examine the role of MAT II activity and SAMe biosynthesis in the survival of leukemic T cells. Inhibition of MAT II and the resultant decrease in SAMe levels enhanced expression of FasL mRNA and protein, and induced DISC (Death Inducing Signaling Complex) formation with FADD (Fas-associated Death Domain) and procaspase-8 recruitment, as well as concomitant increase in caspase-8 activation and decrease in c-FLIP(s) levels. Fas-initiated signaling induced by MAT II inhibition was observed to link to the mitochondrial pathway via Bid cleavage and to ultimately lead to increased caspase-3 activation and DNA fragmentation in these cells. Furthermore, blocking MAT 2A mRNA expression, which encodes the catalytic subunits of MAT II, using a small-interfering RNA approach enhanced FasL expression and cell death, validating the essential nature of MAT II activity in the survival of T leukemic cells.
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PMID:Inhibition of methionine adenosyltransferase II induces FasL expression, Fas-DISC formation and caspase-8-dependent apoptotic death in T leukemic cells. 1904 23