5-ALA mediated PDT induces pyroptosis in colorectal cancer cells by targeting the caspase-1/GSDMD pathway.

Photodynamic therapy (PDT) is a minimally invasive treatment modality based on photochemical reactions that damage specific tumour tissues. Pyroptosis is a type of programmed death that relies on the activation of cysteine-containing aspartate proteolytic enzymes (caspases) and cleavage of the gasdermin protein family members. However, the mechanism of 5-aminolevulinic acid (5-ALA)-mediated PDT-induced pyroptosis in colorectal cancer is not well understood. Here, we found that 5-ALA-mediated PDT can induce pyroptosis in colorectal cancer cells, characterized by the appearance of pyroptotic bubbles and the detection of the release of cellular contents and inflammatory factors. Mechanistically, PDT activates caspase-1 and cleaves gasdermin D (GSDMD), and the release of N-GSDMD triggers pyroptosis in colorectal cancer cells. In addition, inhibition of this pathway in vivo can attenuate the therapeutic effect of PDT. In summary, we investigated the role of GSDMD in PDT-mediated pyroptosis in CRC cells, and the results showed that 5-ALA-mediated PDT induces pyroptosis in colorectal cancer cells by targeting the caspase-1/GSDMD pathway. This study may provide a reference for the clinical application of PDT in CRC treatment.