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

We conducted our study to assess the antiproliferative and proapoptotic potential of hecogenin and tigogenin, two saponins which are structurally similar to diosgenin. We particularly focused our attention on mitogen-activated protein kinase (MAPK) activation in relation to apoptosis but also with the COX-2 expression and activity. Rheumatoid arthritis (RA) synoviocytes were isolated from fresh synovial biopsies obtained from five RA patients undergoing hip arthroplasty. Measurement of cell proliferation was determined using the MTT assay. Apoptosis was evaluated by studying caspase-8, caspase-9 and caspase-3 activities but also by quantification of DNA fragmentation. Quantification of human phospho-MAPKs was realized by ELISA. COX-2 expression was demonstrated by Western blot analysis and COX-2 activity by assay of endogenous prostaglandin E2 (PGE2) production. Tigogenin was more effective than hecogenin in inducing apoptosis in human RA fibroblast-like synoviocytes (FLS) which was caspase dependent but poly(ADP-ribose) polymerase independent and characterized by DNA fragmentation. Our results demonstrated hecogenin- and tigogenin-induced apoptosis through activation of p38 without affecting the JNK and ERK pathways. Indeed, pretreatment with a p38 inhibitor decreased saponin-induced apoptosis with a significant decrease in DNA fragmentation. Furthermore, the rate of apoptosis induced by hecogenin or tigogenin was associated with overexpression of COX-2 correlated with overproduction of endogenous PGE2. These new results provide strong evidence that a family of structurally similar plant steroids is capable of inducing apoptosis in human RA FLS with different rates and different signalling pathways. This study also confirms the discussed appearance of the downregulation or upregulation of COX-2 in cell apoptosis as a function of cell type.
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PMID:Inhibition of human rheumatoid arthritis synovial cell survival by hecogenin and tigogenin is associated with increased apoptosis, p38 mitogen-activated protein kinase activity and upregulation of cyclooxygenase-2. 1778 75

Colorectal cancer is the third most common cause of cancer-related deaths in the world. Surgical intervention followed by chemotherapy remains the primary approach to treatment since colon cancers remain refractory to most chemotherapeutic agents. Based on that, we established a program to screen natural products for cytotoxic activity, employing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay system utilizing HT-29 human colon cancer cells. During the course of our screening, we found that the methanolic extract of silkworm droppings (SDME) has cytotoxic effects on HT-29 cells. In the present study, we investigated the possible mechanisms by which SDME exerts its antiproliferative activity in HT-29 cells. As expected, SDME inhibited growth of HT-29 cells in a dose-dependent manner as assessed by the MTT reduction assay, the lactate dehydrogenase release assay, and the colony formation assay. We also investigated whether the apoptotic effects induced by SDME involve the caspase pathway using the caspase colorimetric assay. Interestingly, caspase-9 and -3, but not caspase-8, were activated in response to SDME treatment. Taken together, these results clearly indicate that the induction of apoptosis by SDME involves a mitochondrial-mediated pathway and strongly suggest that SDME may potentially be a chemotherapeutic agent for human colon cancer.
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PMID:Effect of methanolic extract from silkworm droppings on proliferation and caspase activity in HT-29 human colon cancer cells. 1788 40

The present study was designed to assess the synergistic antitumor effects of anthracenylmethyl homospermidine (ANTMHspd), a novel polyamine conjugate, with alpha-difluoromethylornithine (DFMO) and to elucidate the mechanism of these effects on human leukemia HL60 cells. Cell proliferation was assessed by the MTT assay. Cell cycle, apoptosis and mitochondria membrane potential (MMP) were evaluated by flow cytometry. Caspases and cytochrome c were detected by Western Blot analysis. The combination treatment strongly inhibited cell proliferation, induced cell apoptosis and caused an accumulation in the G1 phase with an accompaniment decrease in S phase. Moreover, reduction of MMP, release of cytochrome c and activation of caspase-3 and caspase-9 but not caspase-8 were observed during the combination-mediated apoptosis. All these findings demonstrated that the combination treatment with DFMO and ANTMHspd resulted in synergistic antitumor effects on HL60 cells.
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PMID:Synergistic antitumor effects of anthracenylmethyl homospermidine and alpha-difluoromethylornithine on promyelocytic leukemia HL60 cells. 1799 55

In this study, we detected the expression of FACL4 mRNA in 40 patients with hepatic carcinoma and its adjacent normal tissues by semi-quantitative RT-PCR. The changes of proliferation and apoptosis of hepatic cancer cell line HepG2 with FACL4 protein expression were examined by MTT and flow cytometry respectively after FACL4 selective inhibitor triacsin C treatment. The activity related to apoptosis of proteinases, caspase-3, caspase-8 and caspase-9, were detected by colorimetry. The expression related to apoptosis of protein, wt-p53, Bax and Bcl-2, in HepG2 cells were evaluated by S-P immunocytochemical dyeing. The results were: (1) FACL4 mRNA was expressed in 95.0% of hepatic cancer tissue, while the positive expression of FACL4 mRNA was 82.5% in cancer adjacent normal liver tissues. Moreover, there was a statistically significant increased in quantity of FACL4 mRNA in cancer tissues compared with adjacent normal liver tissues. (2) The concentration of triacsin C (0.5-2 mg/L) could inhibit the proliferation and induce the apoptosis of HepG2 cells significantly in a dose- and time-effect. (3) During the apoptosis of HepG2 cells induced by triacsin C, flow cytometry coupled with Rhodamine 123 dyeing showed that mitochondrial transmembrane potential of HepG2 declined significantly, and the activity of caspase-9 and caspase-3 increased more remarkably than caspase-8. Besides, the increased apoptosis was accompanied by increased Bax, and decreased wtp53 and Bcl-2 protein levels. The present study suggested that FACL4 might play a role in the growth of hepatic cancer cells. FACL4 selective inhibitor triacsin C leads to a marked growth inhibition of human liver tumor cells, based on the inhibition of proliferation and induction of apoptosis. The apoptotic process was mediated by intrinsic mitochondrial apoptotic pathway due to activation of caspase-9 and caspase-3. The increased apoptosis was accompanied by upregulation of Bax, and decreased wt-p53 and Bcl-2 protein level.
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PMID:The effect of fatty acid-CoA ligase 4 on the growth of hepatic cancer cells. 1805 77

This study was to investigate the cytotoxic effects on pituitary adenoma cell lines GH3/MMQ/AtT20 induced by RGD-FasL and the underlying mechanism. Fas/DcR3 mRNAs were detected by RT-PCR and their surface expressions were measured by flow cytometry. Cytotoxicity exerted by RGD-FasL on tumor cells was measured with MTT assay and the induced apoptosis was determined by agarose gel electrophoresis. The cell cycle and apoptosis was assessed by flow cytometry with PI staining. The expressions of caspase8/9/3, Bcl-2, RANKL and JNK2 were detected by Western blotting. Approximately 13.7% of GH3 cells, 25.5% of MMQ cells, 22.2% of AtT20 cells express Fas, while 23.9% of GH3 cells, 24.1% of MMQ cells, 4.6% of AtT20 cells express DcR3. The cytotoxic effects of FasL/RGD-FasL on tumor cells were all taken in a dose-dependent manner. Cell lines MMQ/AtT20 showed the same sensitivity to RGD-FasL as to FasL, while cell line GH3 was less sensitive to RGD-FasL. The cell cycle analysis indicated that RGD-FasL could inhibit cells in G0/G1 phase and G2/M phase. In MMQ and AtT20 cells treated with RGD-FasL, the AI was not significantly different from that treated with FasL, while in GH3 cells treated with RGD-FasL, the AI was lower than that treated with FasL. The expressions of caspase-8/9/3, RANKL and JNK2 were increased while that of Bcl-2 was decreased after treatment with RGD-FasL, suggesting that RGD-FasL induces apoptosis through caspase activation. We concluded that RGD-FasL could possibly be considered as a novel therapeutical candidate for the treatment of pituitary adenomas.
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PMID:RGD-FasL induces apoptosis of pituitary adenoma cells. 1831 96

Alternol is purified from fermentation productions of microorganisms named as Alternaria alternata var. monosporus. The research is to investigate the apoptosis-inducing effect of alternol on mouse lymphocyte leukemia (L1210) cells and the possible mechanisms. MTT method was used to evaluate the viability of L1210 cells. Apoptosis of L1210 cells was detected by morphological assessment, DNA electrophoresis assay and flow cytometry. Western blotting analysis was carried out to determine the apoptosis-related proteins. Proliferation inhibition of L1210 cells by alternol was found remarkably in a dose-dependent manner. When treated with alternol, apoptotic morphological features of L1210 cells were observed by fluorescent microscopy (AO/EB) and the apoptosis rate was also elevated in a time-dependent manner. After treatments with various concentrations of alternol for 48 h, DNA laddering appeared. The increase of reactive oxygen species (ROS) production was found after cells were exposed to alternol for 6 h, while the decrease of mitochondrial transmembrane potential (delta psi m) was not found until cells were exposed to alternol for 24 h. Furthermore, the level of Bcel-2 and Bcl-2/Bax was down-regulated, while the level of caspase-3 and caspase-9 but not caspase-8 was up-regulated when alternol was added for 72 h. In summary, the results suggested that alternol could inhibit the proliferation of L1210 cells and induce apoptosis of L1210 cells, which was mediated by mitochondria-dependent pathway.
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PMID:[Apoptosis-inducing effect of alternol on mouse lymphocyte leukemia cells and its mechanism]. 1833 38

A quaternary benzo[c]phenanthridine alkaloid chelerythrine displays a wide range of biological activities including cytotoxicity to normal and cancer cells. In contrast, less is known about the biological activity of dihydrochelerythrine, a product of chelerythrine reduction. We examined the cytotoxicity of chelerythrine and dihydrochelerythrine in human promyelocytic leukemia HL-60 cells. After 4h of treatment, chelerythrine induced a dose-dependent decrease in the cell viability with IC50 of 2.6 microM as shown by MTT reduction assay. Dihydrochelerythrine appeared to be less cytotoxic since the viability of cells exposed to 20 microM dihydrochelerythrine for 24h was reduced only to 53%. Decrease in the viability induced by both alkaloids was accompanied by apoptotic events including the dissipation of mitochondrial membrane potential, activation of caspase-9 and -3, and appearance of cells with sub-G1 DNA. Moreover, chelerythrine, but not dihydrochelerythrine, elevated the activity of caspase-8. A dose-dependent induction of apoptosis and necrosis by chelerythrine and dihydrochelerythrine was confirmed by annexin V/propidium iodide dual staining flow cytometry. Besides, both alkaloids were found to induce accumulation of HL-60 cells in G1 phase of the cell cycle. We conclude that both chelerythrine and dihydrochelerythrine affect cell cycle distribution, activate mitochondrial apoptotic pathway, and induce apoptosis and necrosis in HL-60 cells.
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PMID:Chelerythrine and dihydrochelerythrine induce G1 phase arrest and bimodal cell death in human leukemia HL-60 cells. 1835 94

The objective of this study was to investigate the apoptosis-inducing effect and underlying mechanism of naringenin (NGEN) on K562 cells in vitro. The inhibition of NGEN on K562 cells was evaluated by means of MTT assay so as to observe the cytotoxicity of NGEN; The morphological changes of the cells treated by NGEN were observed by transmission electron microscope; cell apoptosis rate influenced by NGEN was assessed by flow cytometry; the enzyme activity changes of caspase-3 and caspase-8 in the process of NGEN-induced K562 apoptosis were detected by Caspase Colorimetric Assay Kit; immunohistochemistry technique was used to detect FAS, FASL protein expression in K562 cells. The results showed that the growth of cells was inhibited by NGEN in dose-and time-dependent manners (p<0.05); NGEN-induced K562 cells apoptosis and sub-G1 peak was observed; some typically early and final phase changes of cell apoptosis were revealed under transmission electron microscope; the enzyme activity of caspase-3 and caspase-8 and the expression of FAS remarkably increased, meanwhile the expression of FASL was down-regulated (p<0.05). It is concluded that NGEN exerts anti-cancer effect by inducing K562 cell apoptosis, and the regulation of the expression of FAS and FASL. The caspase-3 and caspase-8 co-pathway brings about one of the mechanisms.
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PMID:[Relation of apoptosis of K562 cells induced by naringenin in vitro to enzyme activity changes of caspase-3 and caspase-8 and expression of FAS/FASL proteins]. 1842 50

This study shows the effects of L-carnitine treatment on cell proliferation with hepa1c1c7 mouse cancer cells and NCTC 1469 normal cells. In an MTT assay, L-carnitine increased the number of dead hepa1c1c7 cells, while there was no difference in the number of NCTC 1469 cells. mRNA and protein levels of TNF-alpha, Fas, and caspase-8, which are closely related to cell apoptosis by a death ligand/receptor-dependent apoptosis pathway, were increased by L-carnitine treatment. In addition, L-carnitine treatment regulated mitochondria-dependent apoptosis pathways by inducing the up-regulation of caspase-9 and caspase-3 and the down-regulation of Bcl-2 in hepa1c1c 7 cells. Taken together, the findings of this study have demonstrated that L-carnitine could induce apoptosis in hepa1c1c7 cells by regulating Fas ligands and inhibiting the expression of Bcl-2. These results suggest that L: -carnitine treatment could be related to both a mitochondrion-dependent and a death ligand/receptor-dependent apoptosis pathway in hepa1c1c7 cells. Our results could give information for understanding the L-carnitine-induced apoptosis mechanism in some cancer cells.
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PMID:Induction of apoptosis by L-carnitine through regulation of two main pathways in Hepa1c1c 7 cells. 1844 97

Cyclosporin A (CsA), an immunosuppressive drug, has overgrowth effects on human gingival fibroblasts (HGF) in vitro. However, the molecular mechanism responsible for the CsA-induced gingival overgrowth remains still unclear. The present study is aimed to investigate the correlation with the apoptotic signal pathway in CsA-induced overgrowth of HGF. CsA-treated HGF were assessed for cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, for reactive oxygen species (ROS) detection by flow cytometry, for proliferation ability using the 5-bromo-20-deoxyuridine (BrdU), for caspase activities biochemically, for expression of apoptotic signal molecules such as cytochrome c, Fas and Fas-L and Bcl-2 family by Western blotting and VDAC by RT-PCR. CsA increased the cell viability, but not the number of BrdU-positive HGF, indicating that CsA fails to induce the proliferation of HGF. CsA also decreased the intracellular reactive oxygen species level in HGF. This was accompanied by that the antiapoptotic protein Bcl-2 was upregulated whereas the proapoptotic protein Bax was downregulated. Moreover, CsA downregulated VDAC, a mitochondrial transition pore, and decreased the level of cytochrome c released from the mitochondria into the cytosol and activation of caspase-3 and -9 associated with mitochondria-mediated apoptosis. On the other hand, Fas-L level and caspase-8 activation, the major mediator of the death receptor-mediated apoptosis, were diminished in the CsA-treated HGF. CsA inhibits the apoptotic signal molecules such as cytochrome c, caspases and Fas-L with the regulation of Bcl-2 family whereas it has no effect on cell division, which can contribute to overgrowth of HGF. These findings suggest that the decreased apoptosis plays a more important role than the increased cell proliferation in the CsA-induced overgrowth of HGF.
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PMID:Inhibition of apoptotic signals in overgrowth of human gingival fibroblasts by cyclosporin A treatment. 1847 99


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