title: EGCG inhibits Cd(2+)-induced apoptosis through scavenging ROS rather than chelating Cd(2+) in HL-7702 cells.
abstract: OBJECTIVE
  Epigallocatechin-3-gallat (EGCG), the major catechin in green tea, shows a potential protective effect against heavy metal toxicity to humans. Apoptosis is one of the key events in cadmium (Cd(2+))-induced cytotoxicity. Nevertheless, the study of EGCG on Cd(2+)-induced apoptosis is rarely reported. The objective of this study was to clarify the effect and detailed mechanism of EGCG on Cd(2+)-induced apoptosis.
  
  
  METHODS
  Normal human liver cells (HL-7702) were treated with Cd(2+) for 21 h, and then co-treated with EGCG for 3 h. Cell viability, apoptosis, intracellular reactive oxygen species (ROS), malondialdehyde (MDA), mitochondrial membrane potential (MMP) and caspase-3 activity were detected. On the other hand, the chelation of Cd(2+) with EGCG was tested by UV-Vis spectroscopy analysis and Nuclear Magnetic Resonance ((1)H NMR) spectroscopy under neutral condition (pH 7.2).
  
  
  CONCLUSIONS
  Cd(2+) significantly decreased the cell viability and induced apoptosis in HL-7702 cells. Conversely, EGCG co-treatment resulted in significant inhibition of Cd(2+)-induced reduction of cell viability and apoptosis, implying a rescue effect of EGCG against Cd(2+) poisoning. The protective effect most likely arises from scavenging ROS and maintaining redox homeostasis, as the generation of intracellular ROS and MDA is significantly reduced by EGCG, which further prevents MMP collapse and suppresses caspase-3 activity. However, no evidence is observed for the chelation of EGCG with Cd(2+) under neutral condition. Therefore, a clear conclusion from this work can be made that EGCG could inhibit Cd(2+)-induced apoptosis by acting as a ROS scavenger rather than a metal chelating agent.
authors.affiliation: School of Life Sciences, Lanzhou University , Lanzhou, Gansu , China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: An
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Qi
authors.forename: Dejun
authors.initials: D
authors.lastname: Huang
authors.forename: Xueyan
authors.initials: X
authors.lastname: Gu
authors.forename: Yihong
authors.initials: Y
authors.lastname: Tian
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000737:chemistry / Q000633:toxicity*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D002614:Chelating Agents / Q000737:chemistry; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D066244:Proton Magnetic Resonance Spectroscopy; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D002614:Chelating Agents; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D002104:Cadmium; D008315:Malondialdehyde; D002392:Catechin; C045651:epigallocatechin gallate