title: The effect of iron ion on the specificity of photodynamic therapy with 5-aminolevulinic acid.
abstract: Recently, photodynamic therapy using 5-aminolevulinic acid (ALA-PDT) has been widely used in cancer therapy. ALA administration results in tumor-selective accumulation of the photosensitizer protoporphyrin IX (PpIX) via the heme biosynthetic pathway. Although ALA-PDT has selectivity for tumor cells, PpIX is accumulated into cultured normal cells to a small extent, causing side effects. The mechanism of tumor-selective PpIX accumulation is not well understood. The purpose of the present study was to identify the mechanism of tumor-selective PpIX accumulation after ALA administration. We focused on mitochondrial labile iron ion, which is the substrate for metabolism of PpIX to heme. We investigated differences in iron metabolism between tumor cells and normal cells and found that the amount of mitochondrial labile iron ion in cancer was lower than that in normal cells. This finding could be because of the lower expression of mitoferrins, which are the mitochondrial iron transporters. Accordingly, we added sodium ferrous citrate (SFC) with ALA as a source of iron. As a result, we observed the accumulation of PpIX only in tumor cells, and only these cells showed sensitivity to ALA-PDT. Taken together, these results suggest that the uptake abilities of iron ion into mitochondria play a key role in tumor-selective PpIX accumulation. Using SFC as a source of iron might thus increase the specificity of ALA-PDT effects.
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B47, Nagatsuta-cho, Midori-ku, Yokohama, 226-8501, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Department of Urology, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Fukuhara
authors.affiliation: Department of Urology, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Urology, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Shuin
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B47, Nagatsuta-cho, Midori-ku, Yokohama, 226-8501, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Hagiya
authors.affiliation: SBI Pharma CO., LTD., Izumi Garden Tower 20F, 1-6-1, Roppongi Minato-ku, Tokyo, 106-6020, Japan.
authors.forename: Motowo
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: SBI Pharma CO., LTD., Izumi Garden Tower 20F, 1-6-1, Roppongi Minato-ku, Tokyo, 106-6020, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B47, Nagatsuta-cho, Midori-ku, Yokohama, 226-8501, Japan.
authors.forename: Shun-ichiro
authors.initials: S
authors.lastname: Ogura
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D027682:Cation Transport Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D006418:Heme / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D061986:MCF-7 Cells; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000494:pharmacology; D011524:Protoporphyrins / Q000378:metabolism; D012680:Sensitivity and Specificity
chemical_list: D027682:Cation Transport Proteins; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D006418:Heme; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D007501:Iron
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