Chen SH |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=2.376 ------>paper_class3=2 ------>paper_class2=1 ------>vol=594 ------>confirm_bywho=leehorng ------>insert_bywho=ycliang ------>Jurnal_Rank=40.5 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=17 ------>medlineContent= ------>unit=E0310 ------>insert_date=20081010 ------>iam=3 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN= ------>authors_c= ------>score=500 ------>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. ------>confirm_date=20081215 ------>tch_id=089135 ------>pmid=18671963 ------>page1=9 ------>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. ------>tmu_sno=None ------>sno=18874 ------>authors2=Lin JK ------>authors3=Liang YC ------>authors4=Pan MH ------>authors5=Liu SH ------>authors6=Lin-Shiau SY ------>authors6_c= ------>authors=Chen SH ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Involvement of activating transcription factors JNK, NF-kappaB, and AP-1 in apoptosis induced by pyrrolidine dithiocarbamate/Cu complex. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no=1-3 ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2008 ------>submit_flag=None ------>publish_month=1 |