Dormant cancer cells accumulate high protoporphyrin IX levels and are sensitive to 5-aminolevulinic acid-based photodynamic therapy

Taku Nakayama; Shimpei Otsuka; Hideo Fukuhara; Keiji Inoue; Kazuhiro Hanazaki; Taro Shuin; Motowo Nakajima; Tohru Tanaka; Shun-ichiro Ogura

doi:10.1117/12.2524583

7 August 2019 Dormant cancer cells accumulate high protoporphyrin IX levels and are sensitive to 5-aminolevulinic acid-based photodynamic therapy

Taku Nakayama, Shimpei Otsuka, Hideo Fukuhara, Keiji Inoue, Kazuhiro Hanazaki, Taro Shuin, Motowo Nakajima, Tohru Tanaka, Shun-ichiro Ogura

Author Affiliations +

Proceedings Volume 11070, 17th International Photodynamic Association World Congress; 110702H (2019) https://doi.org/10.1117/12.2524583
Event: 17th International Photodynamic Association World Congress, 2019, Cambridge, Massachusetts, United States

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 nondormant 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.

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Citation Download Citation

Taku Nakayama, Shimpei Otsuka, Hideo Fukuhara, Keiji Inoue, Kazuhiro Hanazaki, Taro Shuin, Motowo Nakajima, Tohru Tanaka, and Shun-ichiro Ogura "Dormant cancer cells accumulate high protoporphyrin IX levels and are sensitive to 5-aminolevulinic acid-based photodynamic therapy", Proc. SPIE 11070, 17th International Photodynamic Association World Congress, 110702H (7 August 2019); https://doi.org/10.1117/12.2524583

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