title: Fumonisin B1 does not prevent apoptosis in A431 human epidermoid carcinoma cells after photosensitization with a silicon phthalocyanine.
abstract: 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 maintained 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 accumulation. 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 zVAD, a pan-caspase inhibitor, apoptosis was abolished, while ceramide levels remained elevated after Pc 4-PDT. Exposure of A431 cells to exogenous C6-ceramide for 22 h, led to induction of apoptosis, and the process was abrogated by zVAD. In conclusion, C6-ceramide-, like Pc 4-PDT-induced apoptosis, is zVAD-sensitive. Furthermore, Pc 4 photosensitization can lead to apoptosis without FB-sensitive elevation in ceramide levels upstream of caspases.
authors.affiliation: Department of Radiation Oncology, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4942, USA.
authors.forename: B
authors.initials: B
authors.lastname: Nagy
authors.forename: S M
authors.initials: SM
authors.lastname: Chiu
authors.forename: D
authors.initials: D
authors.lastname: Separovic
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D017209:Apoptosis; D002264:Carboxylic Acids / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism* / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D037341:Fumonisins; D006801:Humans; D007211:Indoles / Q000378:metabolism* / Q000494:pharmacology; D017646:Organosilicon Compounds / Q000378:metabolism / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000378:metabolism* / Q000494:pharmacology; D012821:Silanes; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D051049:Sphingosine N-Acyltransferase; D014407:Tumor Cells, Cultured
chemical_list: D002264:Carboxylic Acids; D002518:Ceramides; D015853:Cysteine Proteinase Inhibitors; D037341:Fumonisins; D007211:Indoles; D017646:Organosilicon Compounds; D017319:Photosensitizing Agents; D012821:Silanes; C107448:phthalocyanine Pc 4; C101954:N-caproylsphingosine; C082854:silicon phthalocyanine; C056933:fumonisin B1; C052464:bis(tri-n-hexylsiloxy)(2,3-naphthalocyaninato)silicon; D000217:Acyltransferases; D051049:Sphingosine N-Acyltransferase; D013108:Sphingomyelin Phosphodiesterase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases