Novel strategy to increase specificity of ALA-Induced PpIX accumulation through inhibition of transporters involved in ALA uptake.

Abstract

Aminolevulinic acid-based photodynamic therapy (ALA-PDT) has emerged as a cancer treatment due to its high specificity and low side effects. In this study, we aimed to identify possible new drugs targeting transporters highly expressed in normal cells but not in cancer cells, to increase the specificity of ALA-PDT. We used a total of seven cell lines, consisting of two gastric, three prostate, and two lung cell lines, for this purpose. siRNAs and inhibitors of these transporters were added, and PpIX production was evaluated using HPLC to examine the roles of transporters in ALA uptake. No correlation in the expression of transporters was observed among cell lines of the same origin. Two major findings were obtained: PEPT1 and PAT1 were expressed only in normal lung and prostate cells, respectively, but not in their cancerous counterparts. The inhibition of these transporters saw a significant decrease in PpIX production only in normal cells, but not in cancer cells. These findings show that the usage of drugs targeted specifically to highly expressed transporters in normal cells is essential for reducing PpIX accumulation in normal cells in order to increase the specificity of ALA-PDT in cancer.