title: Phthalocyanine 4-photodynamic therapy induces ceramide generation and apoptosis in acid sphingomyelinase-deficient mouse embryonic fibroblasts.
abstract: Photodynamic therapy (PDT), a novel cancer treatment using a photosensitizer and visible light, produces an oxidative stress in cells that can lead to apoptosis. PDT with the phthalocyanine photosensitizer Pc 4 (Pc 4-PDT), causes increased generation of ceramide, a lipid mediator, and subsequent induction of apoptosis in various cell types. Formation of ceramide by acid sphingomyelinase (ASMase) in response to stress has been implicated in apoptotic cell death. We assessed the role of ASMase in photocytotoxicity using mouse embryonic fibroblasts (MEFs) isolated from ASMase knockout (k/o) and wild-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 were 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.
authors.affiliation: Department of Radiation Oncology, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4942, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Chiu
authors.forename: T W
authors.initials: TW
authors.lastname: Davis
authors.forename: M
authors.initials: M
authors.lastname: Meyers
authors.forename: N
authors.initials: N
authors.lastname: Ahmad
authors.forename: H
authors.initials: H
authors.lastname: Mukhtar
authors.forename: D
authors.initials: D
authors.lastname: Separovic
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism*; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000378:metabolism*
chemical_list: D002518:Ceramides; D007211:Indoles; D017319:Photosensitizing Agents; C107448:phthalocyanine Pc 4; D013108:Sphingomyelin Phosphodiesterase; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases