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

Area of Science:

• Oncology
• Cell Biology
• Immunology

Background:

• Photodynamic therapy (PDT) is a minimally invasive cancer treatment.
• Pyroptosis is a programmed cell death pathway involving caspases and gasdermins.
• The mechanism of 5-ALA-mediated PDT-induced pyroptosis in colorectal cancer (CRC) remains unclear.

Purpose of the Study:

• To investigate the role of 5-aminolevulinic acid (5-ALA) mediated PDT in inducing pyroptosis in colorectal cancer cells.
• To elucidate the molecular mechanism underlying 5-ALA-PDT-induced pyroptosis in CRC.
• To assess the therapeutic potential of targeting this pathway in CRC treatment.

Main Methods:

• Treatment of colorectal cancer cells with 5-ALA and subsequent photodynamic therapy.
• Analysis of pyroptotic features, including pyroptotic bubbles and release of cellular contents.
• Assessment of caspase-1 activation and gasdermin D (GSDMD) cleavage.
• In vivo studies to evaluate the therapeutic effect of inhibiting the pyroptosis pathway.

Main Results:

• 5-ALA-mediated PDT successfully induced pyroptosis in colorectal cancer cells.
• PDT activated caspase-1, leading to GSDMD cleavage and release of N-GSDMD.
• Inhibition of the caspase-1/GSDMD pathway in vivo attenuated the therapeutic efficacy of PDT.
• Pyroptosis induction was characterized by cellular content release and inflammatory factor secretion.

Conclusions:

• 5-ALA-mediated PDT induces pyroptosis in colorectal cancer cells through the caspase-1/GSDMD pathway.
• Targeting the caspase-1/GSDMD pathway is crucial for the anti-tumor effect of 5-ALA-PDT in CRC.
• This study provides a mechanistic basis for the clinical application of PDT in colorectal cancer treatment.