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Open AccessArticle

The Cisplatin-Derived Increase of Mitochondrial Reactive Oxygen Species Enhances the Effectiveness of Photodynamic Therapy via Transporter Regulation

1
Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan
2
Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan
*
Author to whom correspondence should be addressed.
Cells 2019, 8(8), 918; https://doi.org/10.3390/cells8080918
Received: 26 June 2019 / Revised: 22 July 2019 / Accepted: 16 August 2019 / Published: 17 August 2019
(This article belongs to the Section Cell Signaling and Regulated Cell Death)
Photodynamic therapy (PDT) is a cancer treatment involving the generation of reactive oxygen species (ROS) by laser irradiation of porphyrins that accumulate in cancer tissues. 5-aminolevulinic acid (ALA), a porphyrin precursor, is often used as a photosensitizer. ALA is imported into cells via peptide transporter 1 (PEPT1), and porphyrin is exported via ATP-binding cassette member 2 of subfamily G (ABCG2). Thus, cancer cell-specific porphyrin accumulation involves regulation of both transporters to enhance the ALA-PDT effect. We reported previously that mitochondrial ROS (mitROS) upregulated PEPT1 expression and downregulated ABCG2 expression. Therefore, we propose that increasing mitROS production will enhance ALA-PDT cytotoxicity. Cisplatin is a chemotherapeutic drug that induces intracellular ROS generation. In this study, we investigated whether cisplatin-increased mitROS production in gastric cancer cell lines (RGK36 and RGK45) enhanced the cytotoxicity of ALA-PDT by regulation the expression of both PEPT1 and ABCG2. The results showed that cisplatin increased intracellular mitROS production in cancer but not normal cells (RGM1). PEPT1 was upregulated and ABCG2 downregulated in cancer cells treated with cisplatin. Moreover, intracellular porphyrin accumulation and ALA-PDT cytotoxicity increased. We conclude that cisplatin treatment increases the intracellular mitROS concentration and upregulates PEPT1 and downregulates ABCG2 expression. View Full-Text
Keywords: Photodynamic therapy; cisplatin; 5-aminolevulinic acid; peptide transporter 1; ATP-binding cassette member 2 of subfamily G Photodynamic therapy; cisplatin; 5-aminolevulinic acid; peptide transporter 1; ATP-binding cassette member 2 of subfamily G
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MDPI and ACS Style

Kurokawa, H.; Ito, H.; Matsui, H. The Cisplatin-Derived Increase of Mitochondrial Reactive Oxygen Species Enhances the Effectiveness of Photodynamic Therapy via Transporter Regulation. Cells 2019, 8, 918. https://doi.org/10.3390/cells8080918

AMA Style

Kurokawa H, Ito H, Matsui H. The Cisplatin-Derived Increase of Mitochondrial Reactive Oxygen Species Enhances the Effectiveness of Photodynamic Therapy via Transporter Regulation. Cells. 2019; 8(8):918. https://doi.org/10.3390/cells8080918

Chicago/Turabian Style

Kurokawa, Hiromi; Ito, Hiromu; Matsui, Hirofumi. 2019. "The Cisplatin-Derived Increase of Mitochondrial Reactive Oxygen Species Enhances the Effectiveness of Photodynamic Therapy via Transporter Regulation" Cells 8, no. 8: 918. https://doi.org/10.3390/cells8080918

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