Zinc chelator TPEN induces pancreatic cancer cell death through causing oxidative stress and inhibiting cell autophagy. Issue 11 (3rd May 2019)

• Record Type: Journal Article
• Authors: Yu, Zhen; Yu, Ze; Chen, ZhenBao; Yang, Lin; Ma, MingJun; Lu, ShouNan; Wang, ChunSheng; Teng, ChunBo; Nie, YuZhe
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 11(2019:Nov.)
• Page Start: 20648
• Page End: 20661
• Publication Date: 2019-05-03
• Subjects: autophagy -- lysosome -- mitochondrial metabolism -- ROS -- TPEN; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.28670
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: 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. Previous studies had shown that Zn availability was also important for tumor growth and progression. The aim of the present study was to investigate the potential mechanisms of N, N, N, N‐Tetrakis(2‐pyridylmethyl)‐ethylenediamine (TPEN) (a membrane permeable zinc chelator) induced pancreatic cancer cell death. The text of inductively coupled plasma‐mass spectrometry (ICP‐MS) showed in human pancreatic cancer samples that the zinc content in cancer was higher than that in adjacent tissues. The pancreatic 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 reactive oxygen species (ROS) and restraining autophagy. Our data also indicated that TPEN‐stimulated mitochondrial metabolism produced much ROS. Meanwhile, TPEN reduced the levels of glutathione (GSH) and triggered ROS outbreak, which were 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 disrupting lysosomal by TPEN. Thus, we thought zinc depletion by TPEN was a potential therapeutic strategy for pancreatic cancer. Abstract : TPEN is a membrane‐permeable zinc chelator that decreased the intracellular level of zinc and induced apoptosis. In this investigation, we reported that TPEN induced cell death in pancreatic cancer cells through outbreak of ROS and lysosomal disruption.