Photodynamic therapy induces human esophageal carcinoma cell pyroptosis by targeting the PKM2/caspase-8/caspase-3/GSDME axis

Photodynamic therapy (PDT) uses a photosensitizer (PS) and visible light to induce cancer cell death. Pyroptosis is a new type of programmed cell death that is associated with the gasdermin protein family. However, the precise mechanism of pyroptosis in PDT-induced suppression of esophageal cancer r...

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Bibliographic Details
Published in:Cancer letters 2021-11, Vol.520, p.143-159
Main Authors: Li, Lisha, Song, Dongfeng, Qi, Ling, Jiang, Mingxia, Wu, Yiming, Gan, Junqing, Cao, Kui, Li, Yanjing, Bai, Yuxian, Zheng, Tongsen
Format: Article
Language:English
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Summary:Photodynamic therapy (PDT) uses a photosensitizer (PS) and visible light to induce cancer cell death. Pyroptosis is a new type of programmed cell death that is associated with the gasdermin protein family. However, the precise mechanism of pyroptosis in PDT-induced suppression of esophageal cancer remains unknown. We demonstrate that PDT can induce gasdermin E (GSDME)-mediated pyroptosis, which is characterized by the formation of pyroptotic blebs in esophageal squamous cell carcinoma (ESCC), which burst and release intracellular contents and pro-inflammatory mediators. Mechanistically, PDT may inhibit pyruvate kinase M2 (PKM2) and consequently, activate caspase-8 and caspase-3, which ultimately releases N-GSDME and triggers pyroptosis in ESCC. Moreover, PDT decreased the efficiency of pyroptosis in the presence of a glycolytic inhibitor. Overall, our results show that PDT induces pyroptosis in ESCC by targeting the PKM2/caspase-8/caspase-3/GSDME axis. This is the first in-depth study of the specific mechanism underlying PKM2-mediated pyroptosis under PDT in ESCC, and potentially has great implications for the clinical application of PDT in ESCC. •PDT can induce pyroptosis in human esophageal carcinoma cells.•PDT can induce pyroptosis by targeting PKM2/caspase-8/caspase-3/GSDME pathway.•2-Deoxy-d-glucose has potential for PDT-induced pyroptosis treatment.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2021.07.014