Open AccessThe Specific Inhibition of SOD1 Selectively Promotes Apoptosis of Cancer Cells via Regulation of the ROS Signaling Network
Author(s) -
Xiang Li,
Yuanyuan Chen,
Jidong Zhao,
Jiayuan Shi,
Mingfang Wang,
Shuang Qiu,
Yinghui Hu,
Yan Xu,
Yanfang Cui,
Chunrong Liu
Publication year - 2019
Publication title -
oxidative medicine and cellular longevity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.494
H-Index - 93
eISSN - 1942-0900
pISSN - 1942-0994
DOI - 10.1155/2019/9706792
Subject(s) - signal transduction , microbiology and biotechnology , cancer cell , sod1 , pi3k/akt/mtor pathway , crosstalk , chemistry , apoptosis , mapk/erk pathway , cell signaling , cancer research , protein kinase b , biology , superoxide dismutase , cancer , biochemistry , oxidative stress , genetics , physics , optics
Multiple signaling pathways including ERK, PI3K-Akt, and NF- κ B, which are essential for onset and development of cancer, can be activated by intracellularly sustained high levels of H 2 O 2 provided by elevated activity and expression of copper/zinc superoxide dismutase (SOD1) that catalyzes the dismutation of O 2 •− into H 2 O 2 . 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.