2. Academic Validation
  3. Modified 5-aminolevulinic acid photodynamic therapy induces cutaneous squamous cell carcinoma cell pyroptosis via the JNK signaling pathway

Modified 5-aminolevulinic acid photodynamic therapy induces cutaneous squamous cell carcinoma cell pyroptosis via the JNK signaling pathway

  • Biochim Biophys Acta Mol Cell Res. 2023 Oct 5:119603. doi: 10.1016/j.bbamcr.2023.119603.
Diyan Chen 1,  Bo Wang 2,  Zijun Zhao 1,  Guolong Zhang 1,  Peiru Wang 1,  Linglin Zhang 1,  Xiaojing Liu 1,  Haiyan Zhang 1,  Qingyu Zeng 3,  Xiuli Wang 4
Affiliations

Affiliations

  • 1 Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
  • 2 Avera Medical Group Dermatology, Aberdeen, SD 57401, USA.
  • 3 Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200092, China. Electronic address: zengqingyu2011@tongji.edu.cn.
  • 4 Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200092, China. Electronic address: wangxiuli_1400023@tongji.edu.cn.
PMID: 37805058 DOI: 10.1016/j.bbamcr.2023.119603
Abstract

Modified 5-aminolevulinic acid photodynamic therapy (M-PDT) is a novel therapeutic modality for cutaneous squamous cell carcinoma (cSCC) that is reported to be effective and well tolerated. However, the mechanisms underlying its antitumor effects are not fully understood. In this research, we investigated the effects of M-PDT on Pyroptosis, a form of programmed cell death characterized by cell swelling, ruptures of cell membrane, and inflammatory cytokine release, in two human cSCC cell lines, SCL-1 and HSC-5. We found that M-PDT triggered Pyroptosis in a dose-dependent manner, as evidenced by increased Lactate Dehydrogenase release, propidium iodide staining, and expression of pyroptosis-related proteins, such as NLR family pyrin domain containing 3 (NLRP3), N-terminal of gasdermin D (N-GSDMD), cleaved Caspase-1, and mature interleukin 1 beta (IL-1B) in both cell lines. This process was inhibited by treatment with MCC950, an NLRP3-specific inhibitor, suggesting the involvement of the NLRP3 inflammasome in M-PDT-induced Pyroptosis. We also demonstrated that M-PDT activated c-Jun N-terminal kinase (JNK) signaling, which is required for Pyroptosis induction, as treatment with SP600125, a JNK Inhibitor, suppressed the expression of pyroptosis-related proteins after M-PDT. JNK activation enhanced M-PDT-induced Pyroptosis, highlighting the significance of the JNK pathway in M-PDT. Moreover, M-PDT increased intracellular Reactive Oxygen Species (ROS) levels, which are responsible for JNK activation and Pyroptosis induction. In summary, our results revealed that M-PDT triggers Pyroptosis through ROS-mediated JNK activation and subsequent NLRP3 inflammasome activation in cSCC cells, providing a better understanding of the molecular mechanism of M-PDT and promoting its clinical application.

Keywords

5-aminolevulinic acid; Cutaneous squamous cell carcinoma; JNK; Photodynamic therapy; Pyroptosis; ROS.

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