Photodynamic action of mesoporphyrins on mitochondrial functions and LNCaP cell viability / Ação fotodinamica de meso-porfirinas sobre função mitocondrial e viabilidade de celulas LNCaP

AUTOR(ES)
DATA DE PUBLICAÇÃO

2006

RESUMO

The action of irradiated cationic Fe(III)TMPyP and anionic Fe(III)TPPS4 forms of mesoporphyrins on mitochondrial functions was investigated using experimental conditions that caused minimal effects on mitochondria in the dark. Treatment of mitochondria with 1 µM Fe(III)TMPyP for 2 min decreased the respiratory control by 3% in the dark and 28% after irradiation. Fe(III)TPPS4 (1 µM) had no significant effect on respiratory control under any of the above conditions. Both porphyrins increased mitochondrial production of reactive oxygen species in the presence of Ca2+; however, the effect of Fe(III)TMPyP was significantly stronger. Fe(III)TMPyP but not Fe(III)TPPS4 promoted cyclosporin A-sensitive mitochondrial permeability transition. It was also observed that the association constant of Fe(III)TMPyP with mitochondria was 11 times higher than Fe(III)TPPS4. In conclusion, the damage to isolated mitochondria induced by Fe(III)TMPyP under illumination was larger than by Fe(III)TPPS4, probably because its cationic charge favors association with the mitochondrial membrane. The citotoxic effect of both porphyrins, prior the irradiation and upon the cell viability were dose-dependent and the IC50 were approximatly 15 µM, after 48 hours of incubation. No significantly cytotoxic effect was observed when the tumor cells were treated with 10 µM for each porphyrin, in a time of incubation in the dark of one hour. This was significant only after the photoactivation of the samples. In these conditions, the irradiation of the tumor cells induced cell death both via necrose and apoptose. Cell death via necrose was higher for both porphyrins. Irradiation of both porphyrins significantly increased the cytosolic Ca2+ concentration ([Ca2+]cit) of the LNCaP cells, which mediated cell death, once BAPTA/AM (an intracellular Ca2+ chelator) protected against cell death. Mitochondrial permeability transition (MPT) was probably participating in these mechanisms since cyclosporin A prevented cell death

ASSUNTO(S)

porfirinas oxygen agentes oxidantes bioenergetica photodynamic therapy oxidant agents porphyrins energy metabolism mitochondria fotoquimioterapia oxigenio mitocondria

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