The Specific Inhibition of SOD1 Selectively Promotes Apoptosis of Cancer Cells via Regulation of the ROS Signaling Network

Oxid Med Cell Longev. 2019 Feb 18:2019:9706792. doi: 10.1155/2019/9706792. eCollection 2019.


Multiple signaling pathways including ERK, PI3K-Akt, and NF-κB, which are essential for onset and development of cancer, can be activated by intracellularly sustained high levels of H2O2 provided by elevated activity and expression of copper/zinc superoxide dismutase (SOD1) that catalyzes the dismutation of O2 •- into H2O2. Here, tests performed by the utilization of our designed specific SOD1 inhibitor LD100 on cancer and normal cells reveal that the signaling pathways and their crosstalk to support cancer cell growth are repressed, but the signaling pathways to promote cancer cell cycle arrest and apoptosis are stimulated by specific SOD1 inhibition-mediated ROS changes. These regulated pathways constitute an ROS signaling network that determines the fate of cancer cells. This ROS signaling network is also regulated in SOD1 knockdown cells. These findings might facilitate disclosure of action mechanisms by copper-chelating anticancer agents and design of SOD1-targeting and ROS signaling pathway-interfering anticancer small molecules.

MeSH terms

  • Apoptosis* / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Models, Biological
  • Neoplasms / genetics
  • Neoplasms / pathology*
  • Peroxynitrous Acid / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism*
  • Sequence Analysis, RNA
  • Signal Transduction* / drug effects
  • Superoxide Dismutase-1 / antagonists & inhibitors*
  • Superoxide Dismutase-1 / metabolism
  • Tumor Stem Cell Assay


  • Enzyme Inhibitors
  • RNA, Messenger
  • Reactive Oxygen Species
  • Peroxynitrous Acid
  • Superoxide Dismutase-1