Recombinant human tumor necrosis factor alpha does not potentiate cell killing after photodynamic therapy with a silicon phthalocyanine in A431 humanepidermoid carcinoma cells

Photodynamic therapy (PDT) is a novel cancer treatment utilizing a photosen sitizer, 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 n ot fully understood. Tumor necrosis factor alpha (TNF) is a multifunctional cytokine that has been implicated in photocytotoxicity. We asked whether r ecombinant human TNF (rhTNF) affects Pc 4-PDT cytotoxicity in A431 human ep idermoid 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 cel l survival. In addition, in the presence of Pc 4-PDT or rhTNF, caspase-3 ac tivity and apoptosis were induced. The combined treatment, however, did not potentiate either caspase-3 activity or apoptosis. Similar to previous fin ding we observed that Pc 4-PDT initiated a time-dependent extracellular TNF accumulation. The data suggest that: a) PDT and rhTNF induce cancer cell k illing through different mechanisms; and b) Pc 4-PDT-induced TNF production is a stress response that may not directly affect photocytotoxicity.