THE EFFECT OF A CHALCOGENAPYRYLIUM DYE WITH AND WITHOUT PHOTOLYSIS ON MITOCHONDRIAL FUNCTION IN NORMAL AND TUMOR CELLS

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Abstract
A chalcogenapyrylium dye 8b, which is under investigation for the photodynamic therapy of malignant gliomas (brain tumors), was evaluated for inhibition of mitochondial function both before and after exposure to laser light of 800 m. Neoplastic and normal cells forced to use mitochondrial substrates were killed by the light-activation of intracellular 8b as well as exposure to classic mitochondrial inhibitors, rotenone and sodium azide. Correspondingly, cells in glucose-rich media showed little decrease in viability due to the photolysis of intracellular 8b or the presence of mitochondrial toxins. The toxicity of 8b without light activation was found to be the same regardless of the cell''s energy source. Measurement of cellular ATP generated during treatment also showed the photolysis of intracellular 8b to be more inhibitory towards mitochondrial function than the unactivated parent compound. We conclude that the chalcogenapyrylium dyes localize to the mitochondrion and that photoactivation results in mitochondrial injury.