Relationship of δ-aminolevulinic acid-induced protoporphyrin IX levels to mitochondrial content in neoplastic cells in vitro

Abstract

Protoporphyrin IX, induced by the exogenous addition of δ-aminolevulinic acid, reaches different levels in different tumor cells. Because many of the steps in heme biosynthesis, of which protoporphyrin IX is penultimate, are located in the mitochondria, we surmised that the mitochondrial content of cells may relate to the amount of protoporphyrin IX synthesized in response to excess δ-aminolevulinic acid. We observed that accumulation of MitoTracker, a fluorescent mitochondrial probe, δ- aminolevulinic acid-induced protoporphyrin IX levels, and porphobilinogen deaminase activity all presented with the same cell-line-dependent rank order among the four different neoplastic cells. This rank order, however, differed for cytochrome c oxidase activity, the final enzyme in mitochondrial electron transport, and for accumulation of radioactive label from [14C]δ-aminolevulinic acid. The data demonstrate that enzymes involved in heme biosynthesis, in general, display a rank order associated with mitochondrial content. These data imply that such parameters may have value as prognosticators of cells to produce δ-aminolevulinic acid-induced protoporphyrin IX, a photosensitizer for photodynamic therapy of cancer.