Pyroptosis: a new paradigm of cell death for fighting against cancer

Abstract

Background Unraveling the mystery of cell death is one of the most fundamental progresses of life sciences during the past decades. Regulated cell death (RCD) or programmed cell death (PCD) is not only essential in embryonic development, but also plays an important role in the occurrence and progression of diseases, especially cancers. Escaping of cell death is one of hallmarks of cancer. Main body Pyroptosis is an inflammatory cell death usually caused by microbial infection, accompanied by activation of inflammasomes and maturation of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). Gasdermin family proteins are the executors of pyroptosis. Cytotoxic N-terminal of gasdermins generated from caspases or granzymes proteases mediated cleavage of gasdermin proteins oligomerizes and forms pore across cell membrane, leading to release of IL-1β, IL-18. Pyroptosis exerts tumor suppression function and evokes anti-tumor immune responses. Therapeutic regimens, including chemotherapy, radiotherapy, targeted therapy and immune therapy, induce pyroptosis in cancer, which potentiate local and systemic anti-tumor immunity. On the other hand, pyroptosis of normal cells attributes to side effects of anti-cancer therapies. Conclusion In this review, we focus on the regulatory mechanisms of pyroptosis and the tumor suppressive function of pyroptosis. We discuss the attribution of pyroptosis in reprogramming tumor microenvironments and restoration of anti-tumor immunity and its potential application in cancer immune therapy.

Natural product triptolide induces GSDME-mediated pyroptosis in head and neck cancer through suppressing mitochondrial hexokinase-ΙΙ

“…Pyroptosis is a pro-inflammatory form of regulated cell death. It is characterized by cell swelling and rapid cell rupture, followed by release of proinflammatory interleukin (IL)-1β, IL-18 and other cellular contents to extracellular space [1,2]. Pyroptosis was originally described to occur in Salmonella infected macrophages and is accompanied by caspase-1 activation [3][4][5].…”

Pyroptosis in Cancer: Friend or Foe?

“…In the non-canonical inflammasome pathway, lipopolysaccharide (LPS) directly binds to and activates pro-caspase 4/5 or murine pro-caspase 11. Then, the activated caspases cleave GSDMD, contributing to the oligomerization of the N-terminal in membranes to form pores [ 16 , 17 , 18 , 19 , 20 ], leading to lytic cell death and the release of inflammatory cytokines such as IL-18, IL1β, and HMGB1 [ 21 ]. Later, it was discovered that the gasdermin family GSDMA/B/C/D/E could all be cleaved by activated caspases and granzyme proteases, and the N-terminal oligomerizes in membranes to form pores [ 22 ], leading to pyroptosis ( Figure 1 ).…”

Nod-like Receptors: Critical Intracellular Sensors for Host Protection and Cell Death in Microbial and Parasitic Infections

“…It is noteworthy to mention that the first report of the gasdermin gene (now GSDMA) in the gastrointestinal tract (tightly restricted to the esophagus and stomach) and skin of a mouse was 2000 [ 220 ], and since then, many members of the gasdermin family have been reported; GSDMB, GSDMC, GSDMD, GSDME (also known as DFNA5) and PJVK (also known as DFNB59), with different activating enzymes both in human and mouse [ 221 , 222 , 223 ]. This expansive advancement in the understanding of the gasdermin family and its activating protease enzymes, such as inflammatory caspase 4/5/11 [ 112 , 221 ], non-inflammatory caspase 3/7/8 [ 222 , 223 ], Cathepsin G [ 224 ] and neutrophil elastase [ 225 ], as well as inflammasome activation [ 226 , 227 ], has further broadened the concept of cell death as critical therapeutic targets [ 228 , 229 ] in host immunity [ 230 , 231 ], microbial-induced hyperinflammation [ 140 , 232 ], cytokine storm syndrome [ 228 ] and autoimmune diseases [ 209 , 233 ], as well as in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [ 228 , 234 ]. Today, program cell deaths (PCD), particularly pyroptosis along with others, such as Necroptosis [ 235 ], Ferroptosis [ 236 ], NETosis [ 104 , 237 ], Parthanatos [ 238 ] and PANoptosis [ 133 , 135 ], have received a lot of attention from all facets of research disciplines.…”