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

Sung Ho Chen, Jen Kun Lin, Yu Chih Liang, Min Hsiung Pan, Shing Hwa Liu, Shoei Yn Lin-Shiau

研究成果: 雜誌貢獻文章同行評審

22 引文 斯高帕斯(Scopus)

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.
原文英語
頁(從 - 到)9-17
頁數9
期刊European Journal of Pharmacology
594
發行號1-3
DOIs
出版狀態已發佈 - 十月 10 2008
對外發佈

ASJC Scopus subject areas

  • 細胞與分子神經科學
  • 藥理

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