Heme–porphyrin metabolism in photodynamic therapy associated with reactive oxygen species

Abstract

Photodynamic therapy is a cancer treatment that is minimally invasive and combines photosensitizers with laser irradiation. Among the photosensitizers used in photodynamic therapy, porphyrin compounds have been widely applied because they specifically accumulate in cancer cells, and this approach has already been introduced into clinical practice. However, the detailed mechanism of porphyrin accumulation in cancer cells has not yet been clarified. The authors focused on the structural similarity between heme and porphyrin and demonstrated that the heme carrier protein 1 (HCP1) functions as an importer not only for heme but also for porphyrins. In addition, the expression of HCP1 was found to be regulated by reactive oxygen species (ROS) generated in mitochondria. Certain adjuvant treatments—such as hyperthermia, radiation, and chemical compounds including anticancer drugs—induced mitochondrial ROS production and increased the accumulation of porphyrin compounds through the upregulation of HCP1, thereby enhancing the effectiveness of cancer therapy by laser irradiation. Furthermore, ROS derived from mitochondria were also implicated in the excretion mechanism of porphyrins. Since mitochondria are a major source of ROS through respiratory metabolism, their accurate regulation is essential for optimizing cancer therapy using photodynamic therapy.