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Review
. 2022 Oct;43(10):2462-2473.
doi: 10.1038/s41401-022-00887-6. Epub 2022 Mar 14.

Pyroptosis and pyroptosis-inducing cancer drugs

Fan Yang #  1 , Sahana N Bettadapura #  2 , Mark S Smeltzer  3 , Hua Zhu  4 , Shanzhi Wang  5
Affiliations
Review

Pyroptosis and pyroptosis-inducing cancer drugs

Fan Yang et al. Acta Pharmacol Sin. 2022 Oct.

Abstract

Pyroptosis, an inflammatory form of lytic cell death, is a type of cell death mediated by the gasdermin (GSDM) protein family. Upon recognizing exogenous or endogenous signals, cells undergo inflammasome assembly, GSDM cleavage, the release of proinflammatory cytokines and other cellular contents, eventually leading to inflammatory cell death. In this review, we discuss the roles of the GSDM family for anti-cancer functions and various antitumor drugs that could activate the pyroptosis pathways.

Keywords: GSDMD; GSDME; apoptosis; caspase; inflammasome; pyroptosis.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Roles of caspase-1 and −11 in GSDMD-mediated pyroptosis.
GSDMD is common substrate for both caspase-1 and −11 while pro-IL-18 and pro-IL-1β are only catalyzed by caspase-1.
Fig. 2
Fig. 2. The activation of GSDMD followed by transmembrane pore formation.
Steps 2–4 are based on the conclusions of reference (a). Step 1 is presented in both cartoon and structural views (b). PDB ID: 6N9O (before membrane insertion) and 6VFE (after membrane insertion).
Fig. 3
Fig. 3. Sequence and structural alignment of caspase-1 (green) and caspase-11 (cyan) without CARD domain.
In the structural alignment, dimeric caspase-1 was shown while one of the symmetric monomer of caspase-11 was not shown. PDB ID: 1SC1 (capase-1) and 6KMV (caspase-11).
Fig. 4
Fig. 4. The schematic view of drug-induced pyroptosis in cancer cells.
The names of the pyroptosis-inducing drugs/compounds are in blue. Double arrow means multiple steps are involved, although these steps for TMPs and α-NTEA are not elucidated.
Fig. 5
Fig. 5. PANoptosis during the infection of influenza A virus.
The ZBP1 PANoptosome is simultaneously triggering all three pathways.
See this image and copyright information in PMC

References

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