Cytotoxic effects of the cationic (Fe(III)TMPyP) and anionic (Fe(III)TPPS₄) mesoporphyrins on LNCaP tumor cells prior to irradiation was dose-dependent. The IC₅₀ was about 15 µM, after 48 h of incubation. When incubated in the presence of each of the compounds (10 µM in the dark for 1 h), the irradiation induced both apoptotic (21%) and necrotic (55%) cell death. Chelation of intracelular Ca²⁺ with BAPTA protected LNCaP from porphyrins-induced cell death either by apoptosis or necrosis, suggesting that the higher cytosolic free Ca²⁺ was involved in both processes of cell death. Indeed, irradiation of LNCaP in the presence of each porphyrin resulted in cyclosporin-A sensitive decrease in apoptotic and necrotic cell death. In conclusion, irradiation of these porphyrins increased cytosolic free Ca²⁺ concentrations followed by mitochondrial permeability transition and cell death.