Taipei Medical University

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Chen SH
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------>journal_name=Eur J Pharmacol.
------>paper_name=Involvement of activating transcription factors JNK, NF-kappaB, and AP-1 in apoptosis induced by pyrrolidine dithiocarbamate/Cu complex.
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------>fullAbstract=Pyrrolidine dithiocarbamate (PDTC) is a metal chelator. Biologically, slight toxic affects EC50, 100+/-5.9 microM are observed when added to cultured HL-60 cells. CuCl2 at a physiological concentration (1 microM), but not FeCl2, Pb potentiated the cytotoxic effect of PDTC by 700 fold (EC50, 0.14+/-0.02 microM). 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-kappaB and AP-1 signaling pathways while IkappaB 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-kappaB, AP-1 and caspase 3. Due to its high potency, PDTC may be useful as a therapeutic anti-cancer drug.
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------>authors2=Lin JK
------>authors3=Liang YC
------>authors4=Pan MH
------>authors5=Liu SH
------>authors6=Lin-Shiau SY
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------>authors=Chen SH
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------>updateTitle=Involvement of activating transcription factors JNK, NF-kappaB, and AP-1 in apoptosis induced by pyrrolidine dithiocarbamate/Cu complex.
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------>no=1-3
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------>publish_year=2008
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A B C D E F G H I J K L M N O P Q R S T U V W X Y Z