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

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2019 Mar 27

PMID 30911355

Citations 20

Authors

Xiang Li

Yuanyuan Chen

Jidong Zhao

Jiayuan Shi

Mingfang Wang

Shuang Qiu

Yinghui Hu

Yulin Xu

Yanfang Cui

Chunrong Liu

Changlin Liu

Affiliations

Soon will be listed here.

Abstract

Multiple signaling pathways including ERK, PI3K-Akt, and NF-B, which are essential for onset and development of cancer, can be activated by intracellularly sustained high levels of HO provided by elevated activity and expression of copper/zinc superoxide dismutase (SOD1) that catalyzes the dismutation of O into HO. 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.

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