Cargando…

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

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 pept...

Descripción completa

Detalles Bibliográficos
Autores principales: Kurokawa, Hiromi, Ito, Hiromu, Matsui, Hirofumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721744/
https://www.ncbi.nlm.nih.gov/pubmed/31426474
http://dx.doi.org/10.3390/cells8080918
_version_ 1783448411748433920
author Kurokawa, Hiromi
Ito, Hiromu
Matsui, Hirofumi
author_facet Kurokawa, Hiromi
Ito, Hiromu
Matsui, Hirofumi
author_sort Kurokawa, Hiromi
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6721744
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-67217442019-09-10 The Cisplatin-Derived Increase of Mitochondrial Reactive Oxygen Species Enhances the Effectiveness of Photodynamic Therapy via Transporter Regulation Kurokawa, Hiromi Ito, Hiromu Matsui, Hirofumi Cells Article 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. MDPI 2019-08-17 /pmc/articles/PMC6721744/ /pubmed/31426474 http://dx.doi.org/10.3390/cells8080918 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kurokawa, Hiromi
Ito, Hiromu
Matsui, Hirofumi
The Cisplatin-Derived Increase of Mitochondrial Reactive Oxygen Species Enhances the Effectiveness of Photodynamic Therapy via Transporter Regulation
title The Cisplatin-Derived Increase of Mitochondrial Reactive Oxygen Species Enhances the Effectiveness of Photodynamic Therapy via Transporter Regulation
title_full The Cisplatin-Derived Increase of Mitochondrial Reactive Oxygen Species Enhances the Effectiveness of Photodynamic Therapy via Transporter Regulation
title_fullStr The Cisplatin-Derived Increase of Mitochondrial Reactive Oxygen Species Enhances the Effectiveness of Photodynamic Therapy via Transporter Regulation
title_full_unstemmed The Cisplatin-Derived Increase of Mitochondrial Reactive Oxygen Species Enhances the Effectiveness of Photodynamic Therapy via Transporter Regulation
title_short The Cisplatin-Derived Increase of Mitochondrial Reactive Oxygen Species Enhances the Effectiveness of Photodynamic Therapy via Transporter Regulation
title_sort cisplatin-derived increase of mitochondrial reactive oxygen species enhances the effectiveness of photodynamic therapy via transporter regulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721744/
https://www.ncbi.nlm.nih.gov/pubmed/31426474
http://dx.doi.org/10.3390/cells8080918
work_keys_str_mv AT kurokawahiromi thecisplatinderivedincreaseofmitochondrialreactiveoxygenspeciesenhancestheeffectivenessofphotodynamictherapyviatransporterregulation
AT itohiromu thecisplatinderivedincreaseofmitochondrialreactiveoxygenspeciesenhancestheeffectivenessofphotodynamictherapyviatransporterregulation
AT matsuihirofumi thecisplatinderivedincreaseofmitochondrialreactiveoxygenspeciesenhancestheeffectivenessofphotodynamictherapyviatransporterregulation
AT kurokawahiromi cisplatinderivedincreaseofmitochondrialreactiveoxygenspeciesenhancestheeffectivenessofphotodynamictherapyviatransporterregulation
AT itohiromu cisplatinderivedincreaseofmitochondrialreactiveoxygenspeciesenhancestheeffectivenessofphotodynamictherapyviatransporterregulation
AT matsuihirofumi cisplatinderivedincreaseofmitochondrialreactiveoxygenspeciesenhancestheeffectivenessofphotodynamictherapyviatransporterregulation