https://scholars.lib.ntu.edu.tw/handle/123456789/338478
標題: | Involvement of activating transcription factors JNK, NF-κB, and AP-1 in apoptosis induced by pyrrolidine dithiocarbamate/Cu complex | 作者: | Chen, S.-H. Lin, J.-K. Liang, Y.-C. Pan, M.-H. Liu, S.-H. Lin-Shiau, S.-Y. SHING-HWA LIU MIN-HSIUNG PAN |
關鍵字: | AP-1; Apoptosis; BCPS; Caspase; Copper; JNK; NF-κB; Oxidative stress; PDTC | 公開日期: | 2008 | 卷: | 594 | 期: | 1-3 | 起(迄)頁: | 9-17 | 來源出版物: | European Journal of Pharmacology | 摘要: | Pyrrolidine dithiocarbamate (PDTC) is a metal chelator. Biologically, slight toxic affects EC50, 100 ± 5.9?μM are observed when added to cultured HL-60 cells. CuCl2 at a physiological concentration (1?μM), but not FeCl2, Pb potentiated the cytotoxic effect of PDTC by 700 fold (EC50, 0.14 ± 0.02?μM). Furthermore, results indicated that the PDTC/Cu complex induced an apoptotic process, evidenced by apoptotic bodies, DNA ladder and hypodiploidy cells. Additional studies showed that PDTC/Cu complex significantly decreased mitochondrial membrane potential, increased cytochrome c release, and reactive oxygen species production, and depleted reduced non-protein thiols in a time-dependent manner. Following oxidative stress, the PDTC/Cu complex sequentially activated JNK, NF-κB and AP-1 signaling pathways while IκB kinase activity was enhanced. The apoptotic process was eventually induced by caspase 3 activation and PARP degradation. The non-permeable copper-specific chelator-bathocuproine disulfonate (BCPS) and vitamin C were able to inhibit apoptosis and the elevation of intracellular Cu. Based on these findings; we conclude that PDTC/Cu complex-induced apoptosis is mediated by activation of JNK, NF-κB, AP-1 and caspase 3. Due to its high potency, PDTC may be useful as a therapeutic anti-cancer drug. ? 2008. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-50549096389&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/338478 |
DOI: | 10.1016/j.ejphar.2008.07.024 | SDG/關鍵字: | ascorbic acid; bathocuproine disulfonate; chelating agent; copper; copper chloride; cytochrome c; I kappa B kinase; immunoglobulin enhancer binding protein; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; pyrrolidine dithiocarbamate; reactive oxygen metabolite; stress activated protein kinase; transcription factor AP 1; unclassified drug; apoptosis; article; cell culture; cell level; cell strain HL 60; concentration response; controlled study; culture medium; drug cytotoxicity; drug effect; drug mechanism; drug potency; enzyme activation; enzyme activity; enzyme degradation; enzyme release; human; human cell; mitochondrial membrane potential; priority journal; signal transduction; time; Apoptosis; Caspase 3; Cell Survival; Copper; Cytochromes c; DNA Fragmentation; Electrophoretic Mobility Shift Assay; Flow Cytometry; Free Radicals; HL-60 Cells; Humans; I-kappa B Kinase; JNK Mitogen-Activated Protein Kinases; Membrane Potentials; Mitochondrial Membranes; NF-kappa B; Poly(ADP-ribose) Polymerases; Pyrrolidines; Spectrophotometry, Atomic; Sulfhydryl Compounds; Thiocarbamates; Transcription Factor AP-1 |
顯示於: | 食品科技研究所 |
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