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

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

  • Cancer Lett. 2021 Nov 1;520:143-159. doi: 10.1016/j.canlet.2021.07.014.
Lisha Li 1,  Dongfeng Song 1,  Ling Qi 1,  Mingxia Jiang 1,  Yiming Wu 1,  Junqing Gan 1,  Kui Cao 1,  Yanjing Li 2,  Yuxian Bai 3,  Tongsen Zheng 4
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, 150 Haping St, Nangang District, Harbin, Heilongjiang, 150081, PR China.
  • 2 Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, 150 Haping St, Nangang District, Harbin, Heilongjiang, 150081, PR China. Electronic address: liyanjing_hmu@126.com.
  • 3 Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, 150 Haping St, Nangang District, Harbin, Heilongjiang, 150081, PR China. Electronic address: bai_yuxian@126.com.
  • 4 Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, 150 Haping St, Nangang District, Harbin, Heilongjiang, 150081, PR China. Electronic address: zhengtongsen@126.com.
PMID: 34256094 DOI: 10.1016/j.canlet.2021.07.014
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.

Keywords

Cancer therapy; Photosensitizer; Program cell death; Warburg effect.

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