title: Mitochondrial reactive oxygen species accelerate the expression of heme carrier protein 1 and enhance photodynamic cancer therapy effect.
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.
authors.affiliation: Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nohdai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Ito
authors.affiliation: Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nohdai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nohdai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tamura
authors.affiliation: Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, Japan.
authors.forename: Hideyuki J
authors.initials: HJ
authors.lastname: Majima
authors.affiliation: Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, Japan.
authors.forename: Hiroko P
authors.initials: HP
authors.lastname: Indo
authors.affiliation: Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nohdai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Ichinosuke
authors.initials: I
authors.lastname: Hyodo
keywords: gastric epithelial cell; hematoporphyrin derivatives (HpD); heme carrier protein 1 (HCP-1); mitROS; photodynamic therapy