C6-pyridinium ceramide sensitizes SCC17B human head and neck squamous cell carcinoma cells to photodynamic therapy

• PDT + C6-pyridinium ceramide (LCL29) enhance caspase-dependent cell death.
• Ceramide synthase inhibitor fumonisin B1 (FB) rescues cells from death post-PDT ± LCL29.
• PDT + LCL29 enhance FB-sensitive mitochondrial ceramide accumulation.
• PDT + LCL29 enhance FB-sensitive cytochrome c redistribution.
• PDT + LCL29 enhance FB-sensitive caspase-3 activation.

Combining photodynamic therapy (PDT) with another anticancer treatment modality is an important strategy for improved efficacy. PDT with Pc4, a silicon phthalocyanine photosensitizer, was combined with C6-pyridinium ceramide (LCL29) to determine their potential to promote death of SCC17B human head and neck squamous cell carcinoma cells. PDT + LCL29-induced enhanced cell death was inhibited by zVAD-fmk, a pan-caspase inhibitor, and fumonisin B1 (FB), a ceramide synthase inhibitor. Quantitative confocal microscopy showed that combining PDT with LCL29 enhanced FB-sensitive ceramide accumulation in the mitochondria. Furthermore, PDT + LCL29 induced enhanced FB-sensitive redistribution of cytochrome c and caspase-3 activation. Overall, the data indicate that PDT + LCL29 enhanced cell death via FB-sensitive, mitochondrial ceramide accumulation and apoptosis.