Reactive Oxygen Species Involved Cancer Cellular Specific 5-Aminolevulinic Acid Uptake

Photodynamic therapy (PDT) and photodynamic diagnosis (PDD) using 5-aminolevulinic acid (ALA) are clinically useful for cancer treatments. Cancer cells have been reported that ALA is incorporated via peptide transporter 1 (PEPT1), which is one of the membrane transport proteins, and has been reported to be significantly expressed in various gastrointestinal cancer cells such as Caco-2. However, the mechanism of this protein expression has not been elucidated. Concentration of Reactive oxygen species (ROS) is higher in cancer cells in comparison with that of normal cells. We have previously reported that ROS derived from mitochondria (mitROS) is likely related to invasions and proliferations of cancer cells. Since ALA is the most important precursor of heme which is necessary protein for cellular proliferations, mitROS may be also related to PEPT1 expressions. In this study, We used a rat gastric mucosal cell line RGM1 and its cancer-like mutated cell line RGK1, and we clarified the ALA uptake mechanism and its relations between mitROS and PEPT1 expression in RGK1. We also used our self-established stable clone of cell which over-expresses manganese superoxide dismutase, a mitROS scavenger. We studied differences of the PDT effects in these cells after ALA administrations to clear the influence of mitROS.