Sanguinarine activates ATM/ATR-mediated CHK-1 signaling to drive p53-dependent apoptosis in the C. elegans germline

Abstract

Sanguinarine (SNG) is a natural component belonging to the benzophenanthridine alkaloids. In recent years, due to its remarkable biological activities, it has gained wide interest in the pharmaceutical industry. Various studies have reported its potential as a therapeutic agent in treating chronic human diseases such as cancer. SNG is widely reported to cause programmed cell death in various cancer cell lines. The mechanism by which SNG triggers apoptosis remains poorly elucidated, especially in vivo. Previous studies reported that sanguinarine induces apoptosis by increasing reactive oxygen species (ROS). In this study, we aimed to characterize the effects of SNG using an in vivo Caenorhabditis elegans (C. elegans) model. Treating C. elegans with various SNG concentrations resulted in apoptotic cell death in the proliferative germline. Interestingly, SNG-induced apoptosis depends on the core apoptotic machinery initiated by the DNA-damage-induced activity of the p53/CEP-1 protein. We have also demonstrated that the increase in germ cell apoptosis is caused by elevated levels of reactive oxygen species (ROS) following SNG treatment. Notably, the apoptotic phenotype induced by SNG was resolved upon treatment with the ROS scavenger. Altogether, our study demonstrates that SNG increases ROS, leading to activation of DNA damage-induced apoptosis in the proliferative germline of C. elegans.