ABSTRACT
Photodynamic therapy using hematoporphyrin and its derivatives is clinically useful for cancer treatments. It has been reported that cancer cells incorporate hematoporphyrin and its derivatives via heme carrier protein 1, which is a proton-coupled folate transporter. However, the mechanism of this protein expression has not been elucidated. In general, the concentration of reactive oxygen species in cancer cells is higher than that in normal cells. We previously reported that reactive oxygen species from mitochondria involved in the expression of peptide transporter 1 and accelerate the uptake of 5-aminolevulinic acid, which is a precursor of protoporphyrin IX. We suggested mitochondrial reactive oxygen species also regulated the expression of heme carrier protein 1. In this study, we used a rat gastric mucosal cell line RGM1 and its cancer-like mutated cell line RGK1. We clarified the expression of heme carrier protein 1 increased in cancer cells and it decreased in manganese superoxide dismutase expressed cancer cells. In addition, the uptake level of hematoporphyrin and photodynamic therapeutic effect were also decreased in manganese superoxide dismutase expressed cancer cells in comparison with cancer cells. Thus, we concluded that mitochondrial reactive oxygen species regulated heme carrier protein 1 expression and photodynamic therapeutic effect.
ABSTRACT
The in vivo photosensitizing efficacy of chlorophyll derivatives(CpD), which had been developed as a new photosensitizer, was compared with that of hematoporphyrin derivatives (HpD). A murine tumor model implanted subcutaneously with S-180 cells on the abdomen was used. The CpD or HpD was administered by intratumoral injection, and light of appropriate wavelength was irradiated on the tumor areas for 10 minutes at 1h and 24h or 24h and 48h after the injection of photosensitizer. When CpD was injected, the early irradiation group (1h and 24h) showed a 100% tumor cure rate; however, the late irradiation group (24h and 48h) showed a 60% tumor cure rate (p less than 0.01). This showed that the early irradiation with light after injection of CpD was an important factor for obtaining better results. With HpD, there was no difference in tumor cure rate between early (1h and 24h, 80%) and late irradiation (24h and 48h, 80%) groups. Thus, in early irradiation groups, the tumor cure rate using CpD (100%) was superior to that of HpD (80%) (p less than 0.05). However, in late irradiation groups, the tumor cure rate using CpD (60%) was inferior to that of HpD (80%), but this difference was not statistically significant (p greater than 0.1). Pathologic sections of these tumors were made before treatment and 48h and 3 weeks after treatment. These showed geographic necrosis at 48h after treatment and no viable tumor tissue at 3 weeks after treatment. Our results showed that CpD was as effective as HpD as a photosensitizer for in vivo photodynamic therapy.
Subject(s)
Mice , Abdomen , Animals , Chlorophyll/analogs & derivatives , Mice, Inbred ICR , Photochemotherapy/methods , Sarcoma, Experimental/drug therapy , Skin Neoplasms/drug therapyABSTRACT
The in vivo photosensitizing efficacy of chlorophyll derivatives(CpD), which had been developed as a new photosensitizer, was compared with that of hematoporphyrin derivatives (HpD). A murine tumor model implanted subcutaneously with S-180 cells on the abdomen was used. The CpD or HpD was administered by intratumoral injection, and light of appropriate wavelength was irradiated on the tumor areas for 10 minutes at 1h and 24h or 24h and 48h after the injection of photosensitizer. When CpD was injected, the early irradiation group (1h and 24h) showed a 100% tumor cure rate; however, the late irradiation group (24h and 48h) showed a 60% tumor cure rate (p less than 0.01). This showed that the early irradiation with light after injection of CpD was an important factor for obtaining better results. With HpD, there was no difference in tumor cure rate between early (1h and 24h, 80%) and late irradiation (24h and 48h, 80%) groups. Thus, in early irradiation groups, the tumor cure rate using CpD (100%) was superior to that of HpD (80%) (p less than 0.05). However, in late irradiation groups, the tumor cure rate using CpD (60%) was inferior to that of HpD (80%), but this difference was not statistically significant (p greater than 0.1). Pathologic sections of these tumors were made before treatment and 48h and 3 weeks after treatment. These showed geographic necrosis at 48h after treatment and no viable tumor tissue at 3 weeks after treatment. Our results showed that CpD was as effective as HpD as a photosensitizer for in vivo photodynamic therapy.
