The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
Chemotherapy-induced pyroptosis is mediated by BAK/BAX-caspase-3-GSDME pathway and inhibited by 2-bromopalmitate
Open accessAbstract
Many chemotherapy treatments induce apoptosis or pyroptosis through BAK/BAX-dependent mitochondrial pathway. BAK/BAX activation causes the mitochondrial outer membrane permeabilization (MOMP), which induces the activation of pro-apoptotic caspase cascade. GSDME cleavage by the pro-apoptotic caspases determines whether chemotherapy drug treatments induce apoptosis or pyroptosis, however, its regulation mechanisms are not clear. In this study, we showed that TNFα+CHX and navitoclax-induced cancer cell pyroptosis through a BAK/BAX-caspase-3-GSDME signaling pathway. GSDME knockdown inhibited the pyroptosis, suggesting the essential role of GSDME in this process. Interestingly, GSDME was found to be palmitoylated on its C-terminal (GSDME-C) during chemotherapy-induced pyroptosis, while 2-bromopalmitate (2-BP) could inhibit the GSDME-C palmitoylation and chemotherapy-induced pyroptosis. Mutation of palmitoylation sites on GSDME also diminished the pyroptosis induced by chemotherapy drugs. Moreover, 2-BP treatment increased the interaction between GSDME-C and GSDME-N, providing a potential mechanism of this function. Further studies indicated several ZDHHC proteins including ZDHHC-2,7,11,15 could interact with and palmitoylate GSDME. Our findings offered new targets to achieve the transformation between chemotherapy-induced pyroptosis and apoptosis.
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Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death
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Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin
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Two CD95 (APO‐1/Fas) signaling pathways
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Cited by
Yan, H., Luo, B., Wu, X., Guan, F., Yu, X., Zhao, L., Ke, X., Wu, J., & Yuan, J. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.60292 · Cited by 303
Cleavage of CAD by caspase-3 determines the cancer cell fate during chemotherapy
Ma, J., Zhao, J., Zhang, C., Tan, J., Cheng, A., Niu, Z., Lin, Z., Pan, G., Chen, C., Ding, Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60144-2 · Cited by 14
Metadata
- Authors
- Hu, L., Chen, M., Chen, X., Zhao, C., Fang, Z., Wang, H., & Dai, H.
- Venue
- Cell Death & Disease
- Published
- 2020-04-24
- Volume
- 11
- Issue
- 4
- Pages
- 281-281
- ISSN
- 2041-4889 (ISSN-L)
- OpenAlex
- W3018541786
- Cited by
- 319
- References
- 64
- FWCI
- 10.86
- Type
- journal article
- Language
- en
- Open access
- gold
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- Hu, L., Chen, M., Chen, X., Zhao, C., Fang, Z., Wang, H., & Dai, H. (2020). Chemotherapy-induced pyroptosis is mediated by BAK/BAX-caspase-3-GSDME pathway and inhibited by 2-bromopalmitate. Cell Death & Disease. https://doi.org/10.1038/s41419-020-2476-2
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