title: Dormant cancer cells accumulate high protoporphyrin IX levels and are sensitive to 5-aminolevulinic acid-based photodynamic therapy.
abstract: Photodynamic therapy (PDT) and diagnosis (PDD) using 5-aminolevulinic acid (ALA) to drive the production of an intracellular photosensitizer, protoporphyrin IX (PpIX), are in common clinical use. However, the tendency to accumulate PpIX is not well understood. Patients with cancer can develop recurrent metastatic disease with latency periods. This pause can be explained by cancer dormancy. Here we created uniformly sized PC-3 prostate cancer spheroids using a 3D culture plate (EZSPHERE). We demonstrated that cancer cells exhibited dormancy in a cell density-dependent manner not only in spheroids but also in 2D culture. Dormant cancer cells accumulated high PpIX levels and were sensitive to ALA-PDT. In dormant cancer cells, transporter expressions of PEPT1, ALA importer, and ABCB6, an intermediate porphyrin transporter, were upregulated and that of ABCG2, a PpIX exporter, was downregulated. PpIX accumulation and ALA-PDT cytotoxicity were enhanced by G0/G1-phase arrestors in non-dormant cancer cells. Our results demonstrate that ALA-PDT would be an effective approach for dormant cancer cells and can be enhanced by combining with a cell-growth inhibitor.
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 B47, Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 B47, Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Shimpei
authors.initials: S
authors.lastname: Otsuka
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 B47, Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 B47, Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Hodaka
authors.initials: H
authors.lastname: Okajima
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 B47, Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsumoto
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: Department of Urology, Kochi Medical School, Kohasu, Okocho, Nankoku, Kochi, 783-8505, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Urology, Kochi Medical School, Kohasu, Okocho, Nankoku, Kochi, 783-8505, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Shuin
authors.affiliation: SBI Pharmaceuticals 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 Pharmaceuticals 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: SI
authors.lastname: Ogura
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D011524:Protoporphyrins / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects
chemical_list: D014408:Biomarkers, Tumor; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX