engleski

Fumonisin B1 does not prevent apoptosis in A431 human epidermoid carcinoma cells after photosensitization with phthalocyanine 4

Photodynamic therapy with the phthalocyanine photosensitizer Pc 4 (Pc 4-PDT), an apoptosis inducer, is associated with accumulation of ceramide in various cell lines. The role of ceramide in Pc 4-PDT-induced apoptosis was investigated in A431 cells. Caspase-3 (casp-3) was activated and TUNEL positive cells began to appear 30 and 60 min post-Pc 4-PDT, respectively. A rapid increase (10 min) in cellular ceramide levels was observed after Pc 4-PDT. Induced ceramide accumulation was maintaned over 60 min. Acid sphingomyelinase, a ceramide-generating enzyme, was inhibited after photosensitization with pC 4, suggesting that the enzyme was not required for stimulated ceramide accumularion. Co-treatment of A431 cells with fumonisin B1, a ceramide synthase inhibitor, and Pc 4-PDT led to a decrease in ceramide levels without any effect on induced casp-3 activity or apoptosis. In the presence of zVADfmk, a pancaspase inhibitor, apoptosis was abolished, while ceramide levels remained elevated after pc4-PDT. Exposure of A431 cells to exogenous C6-ceramide for 22 h, led to induction of apoptosis, and the process was abrogated by zVADfmk. In conclusion, C6-ceramide, like Pc 4-PDT-induced apoptosis, is zVADfmk-sensitive. Furthermore, Pc 4 photosensitization can lead to apoptosis without FB-sensitive elevation in ceramide levels upstream of caspases.

apoptosis; ceramide; ceramide synthase; photodynamic therapy

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