Photodynamic therapy induces human esophageal carcinoma cell pyroptosis by targeting the PKM2/caspase-8/caspase-3/GSDME axis. (1st November 2021)

• Record Type: Journal Article
• Authors: Li, Lisha; Song, Dongfeng; Qi, Ling; Jiang, Mingxia; Wu, Yiming; Gan, Junqing; Cao, Kui; Li, Yanjing; Bai, Yuxian; Zheng, Tongsen
• Is Part Of: Cancer letters. Volume 520(2021)
• Page Start: 143
• Page End: 159
• Publication Date: 2021-11-01
• Subjects: Photosensitizer -- Cancer therapy -- Warburg effect -- Program cell death; PDT photodynamic therapy -- ESCC esophageal squamous carcinoma cell -- PS photosensitizer -- ROS reactive oxygen species -- PKM2 Pyruvate kinase M2 -- GSDME gasdermin E -- IL interleukin -- DFNA5 deafness autosomal dominant 5 -- FBS fetal bovine serum -- DMSO Dimethyl sulfoxide -- CCK-8 Counting Kit-8 -- TNF-α tumor Necrosis Factor Alpha -- IL1-α Interleukin 1 Alpha -- IL-1β Interleukin 1 Beta -- IL-6 Interleukin 6 -- IFN-γ Interferon Gamma -- ELISA enzyme-linked immunosorbent assay -- LDH lactate dehydrogenase -- PI propidium iodide -- OsO4 osmium tetraoxide -- V volume -- NC negative control -- DDP cisplatin -- AIF alpinumisoflavone -- 2-DG 2-Deoxy-D-arabino-hexose; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2021.07.014
• Languages: English
• ISSNs: 0304-3835

Abstract

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. Highlights: 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.