Involvement of activating transcription factors JNK;  NF-kappaB;  and AP-1 in apoptosis induced by pyrrolidine dithiocarbamate/Cu complex.

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Title:	Involvement of activating transcription factors JNK;NF-kappaB;and AP-1 in apoptosis induced by pyrrolidine dithiocarbamate/Cu complex.
Authors:	梁有志 Chen SH;Lin JK;Liang YC;Pan MH;Liu SH;Lin-Shiau SY
Contributors:	醫學檢驗暨生物技術學系
Keywords:	PDTC;copper;oxidative stress;JNK;NF-kappa B;AP-1;caspase;apoptosis;BCPS
Date:	2008
Issue Date:	2009-08-25 10:38:35 (UTC+8)
Abstract:	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.
Relation:	Eur J Pharmacol.(594):9-17.
Data Type:	article
Appears in Collections:	[ ] Periodical Articles

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