ROS induced pyroptosis in inflammatory disease and cancer

Abstract

Pyroptosis, a form of caspase-1-dependent cell death, also known as inflammation-dependent death, plays a crucial role in diseases such as stroke, heart disease, or tumors. Since its elucidation, pyroptosis has attracted widespread attention from various sectors. Reactive oxygen species (ROS) can regulate numerous cellular signaling pathways. Through further research on ROS and pyroptosis, the level of ROS has been revealed to be pivotal for the occurrence of pyroptosis, establishing a close relationship between the two. This review primarily focuses on the molecular mechanisms of ROS and pyroptosis in tumors and inflammatory diseases, exploring key proteins that may serve as drug targets linking ROS and pyroptosis and emerging fields targeting pyroptosis. Additionally, the potential future development of compounds and proteins that influence ROS-regulated cell pyroptosis is anticipated, aiming to provide insights for the development of anti-tumor and anti-inflammatory drugs.

Keywords: ROS; cell death; inflammation; pyroptosis; tumor.

Figure 1

Various pathways induced pyroptosis by mediating caspase and gasdermin families (1). LPS induced caspase-11-dependent cleavage of the pannexin-1 channel and ATP release. (2) LPS stimulated NLRP1b and activate pro-caspase-1-mediated cell death. (3) ROS induced GSDME-dependent pyroptosis. (4) Inhibition of TAK1 by pathogenic Yersinia triggered RIPK1or caspase-8-dependent cleavage of GSDMD. (5) α-ketoglutarate induced pyroptosis through caspase-8-mediated cleavage of GSDMC. (6) GAS actived SpeB and triggered the release of active N-terminal fragments of keratinocytes through cleaving GSDMA after Gln246.

Figure 2

Overproduction of ROS activated NLRP3 and promoted the formation of inflammasome and cleaved the GSDMD due to caspase-1 activation.

Figure 3

Differences of ROS regulates pyroptosis in tumor and inflammatory diseases.