Phthalocyanine 4-photodynamic therapy induces ceramide generation and apoptosis in acid sphingomyelinase-deficient mouse embryonic fibroblasts

Photodynamic therapy (PDT), a novel cancer treatment using a photosensitize r and visible light, produces an oxidative stress in cells that can lead to apoptosis. PDT with the phthalocyanine photosensitizer Pc 4 (Pc 4-PDT), ca uses increased generation of ceramide, a lipid mediator, and subsequent ind uction of apoptosis in various cell types. Formation of ceramide by acid sp hingomyelinase (ASMase) in response to stress has been implicated in apopto tic cell death. We assessed the role of ASMase in photocytotoxicity using m ouse embryonic fibroblasts (MEFs) isolated from ASMase knockout (k/o) and w ild-type (wt) mice. Exposure of wt or k/o MEFs to Pc 4-PDT led to increased caspase-3 activity and subsequent apoptosis. Similarly, ceramide levels we re elevated in both cell types post-PDT. We suggest that in MEFs, ASMase is dispensable for ceramide accumulation and induction of apoptosis after Pc 4-PDT.