Study Of Zinc Chelator TPEN-induced Pancreatic Cancer Cell Death

The essential trace element zinc(Zn)is widely required in cellular functions,and abnormal Zn homeostasis causes a variety of health problems including immunodeficiency and sensory dysfunctions.It has also been reported that zinc chelating agent TPEN(N,N,N,N-tetrakis(2-pyridylmethyl)-ethylenediamine)plays a role in inducing apoptosis in some types of cells,and the cytotoxic mechanism of TPEN is different in different tumor cell lines.The am of the present study was to investigate the potential mechanisms of TPEN induced pancreatic cancer cells death.The text of ICP-MS showed in human pancreatic cancer samples,the zinc content in eancer was higher than that in adjacent tissues.The pancreatie cancer cell lines Panc-1,8988T,BxPc-3 and L3.6 were used in this study.Our results indicated that TPEN markedly induced cell death,via increasing ROS and restraining autophagy.Our data also indicated that TPEN stimulated mitochondrial metabolism,produced much ROS.Meanwhile,TPEN reduced the levels of GSH,triggered ROS outbreak was the main causes of cell death.In addition,cell autophagy was significantly depressed in Panc-1 cells treated by TPEN,which was due to the ability of disrapting Lysosomal by TPEN.Thus,we concluded zinc depletion by TPEN was a potential therapeutic strategy for pancreatic cancer.