title: Recombinant human tumor necrosis factor alpha does not potentiate cell killing after photodynamic therapy with a silicon phthalocyanine in A431 human epidermoid carcinoma cells.
abstract: Photodynamic therapy (PDT) is a novel cancer treatment utilizing a photosensitizer, visible light and oxygen. PDT with the silicon phthalocyanine Pc 4, a new photosensitizer, is highly effective in cancer cell destruction and tumor ablation. The mechanisms underlying cancer cell killing by PDT are not fully understood. Tumor necrosis factor alpha (TNF) is a multifunctional cytokine that has been implicated in photocytotoxicity. We asked whether recombinant human TNF (rhTNF) affects Pc 4-PDT cytotoxicity in A431 human epidermoid carcinoma cells. Co-treatment of A431 cells with various doses of Pc 4-PDT and a sub-lethal rhTNF dose led to a sub-additive reduction in cell survival. In addition, in the presence of Pc 4-PDT or rhTNF, caspase-3 activity and apoptosis were induced. The combined treatment, however, did not potentiate either caspase-3 activity or apoptosis. Similar to previous findings we observed that Pc 4-PDT initiated a time-dependent extracellular TNF accumulation. The data suggest that: a) PDT and rhTNF induce cancer cell killing through different mechanisms; and b) Pc 4-PDT-induced TNF production is a stress response that may not directly affect photocytotoxicity.
authors.affiliation: Department of Radiation Oncology, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4942, USA.
authors.forename: K
authors.initials: K
authors.lastname: Azizuddin
authors.forename: K
authors.initials: K
authors.lastname: Kalka
authors.forename: S M
authors.initials: SM
authors.lastname: Chiu
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: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D017646:Organosilicon Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D012821:Silanes; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D007211:Indoles; D017646:Organosilicon Compounds; D017319:Photosensitizing Agents; D012821:Silanes; D014409:Tumor Necrosis Factor-alpha; C082854:silicon phthalocyanine; C052464:bis(tri-n-hexylsiloxy)(2,3-naphthalocyaninato)silicon; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases