1. Photodynamic therapy induces human esophageal carcinoma cell pyroptosis by targeting the PKM2/caspase-8/caspase-3/GSDME axis
- Author
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Yuxian Bai, Lisha Li, Junqing Gan, Tongsen Zheng, Yiming Wu, Dongfeng Song, Yanjing Li, Mingxia Jiang, Ling Qi, and Kui Cao
- Subjects
Male ,Thyroid Hormones ,Cancer Research ,Programmed cell death ,medicine.medical_treatment ,Photodynamic therapy ,Caspase 3 ,PKM2 ,Caspase 8 ,Mice ,Cell Line, Tumor ,Pyroptosis ,medicine ,Animals ,Humans ,Cell Proliferation ,Chemistry ,Membrane Proteins ,eye diseases ,Gene Expression Regulation, Neoplastic ,Photochemotherapy ,Receptors, Estrogen ,Oncology ,Cancer cell ,Cancer research ,Heterografts ,Female ,Esophageal Squamous Cell Carcinoma ,Cisplatin ,Carrier Proteins ,Intracellular - Abstract
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.
- Published
- 2021