Preclinical Validation of Talaporfin Sodium-Mediated Photodynamic Therapy for Esophageal Squamous Cell Carcinoma

Photodynamic therapy (PDT) kills cancer cells via a photochemical reaction mediated by an oncotropic photosensitizer. Herein, we performed an experimental preclinical study to validate the anti-tumour effect of talaporfin sodium-mediated PDT (t-PDT) for esophageal squamous cell carcinoma (ESCC) cell...

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Main Authors: Ohashi, Shinya, Kikuchi, Osamu, Tsurumaki, Mihoko, Nakai, Yukie, Kasai, Hiroi, Horimatsu, Takahiro, Miyamoto, Shin'ichi, Shimizu, Akira, Chiba, Tsutomu, Muto, Manabu
Format: Online
Language:English
Published: Public Library of Science 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121166/
id pubmed-4121166
recordtype oai_dc
spelling pubmed-41211662014-08-05 Preclinical Validation of Talaporfin Sodium-Mediated Photodynamic Therapy for Esophageal Squamous Cell Carcinoma Ohashi, Shinya Kikuchi, Osamu Tsurumaki, Mihoko Nakai, Yukie Kasai, Hiroi Horimatsu, Takahiro Miyamoto, Shin'ichi Shimizu, Akira Chiba, Tsutomu Muto, Manabu Research Article Photodynamic therapy (PDT) kills cancer cells via a photochemical reaction mediated by an oncotropic photosensitizer. Herein, we performed an experimental preclinical study to validate the anti-tumour effect of talaporfin sodium-mediated PDT (t-PDT) for esophageal squamous cell carcinoma (ESCC) cells. We used human ESCC cells derived from various differentiation grades or resistant to 5-fluorouracil (5-FU). The cytotoxic effect of t-PDT was determined by evaluating cell viability, apoptosis and generation of reactive oxygen species (ROS) and DNA double-strand breaks. Furthermore, the anti-tumour effect of t-PDT was assessed using an anchorage-independent cell-growth assay and xenograft transplantation models. t-PDT induced potent cytotoxicity in ESCC cells independent of their differentiation grade or 5-FU resistance. Moreover, t-PDT induced robust apoptosis, as indicated by cell shrinkage, perinuclear vacuolization, nuclear fragmentation and induction of annexin V-positive cells. This apoptotic response was accompanied by concurrent activation of ROS, and induction of DNA double-strand breakage. Importantly, t-PDT suppressed efficiently anchorage-independent cell growth as well as ESCC-xenografted tumor formation. In aggregate, t-PDT showed anti-tumor potential for ESCC cells with various histological grades or chemoresistance, providing a novel translational rationale of t-PDT for the treatment of ESCC. Public Library of Science 2014-08-04 /pmc/articles/PMC4121166/ /pubmed/25090101 http://dx.doi.org/10.1371/journal.pone.0103126 Text en © 2014 Ohashi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Ohashi, Shinya
Kikuchi, Osamu
Tsurumaki, Mihoko
Nakai, Yukie
Kasai, Hiroi
Horimatsu, Takahiro
Miyamoto, Shin'ichi
Shimizu, Akira
Chiba, Tsutomu
Muto, Manabu
spellingShingle Ohashi, Shinya
Kikuchi, Osamu
Tsurumaki, Mihoko
Nakai, Yukie
Kasai, Hiroi
Horimatsu, Takahiro
Miyamoto, Shin'ichi
Shimizu, Akira
Chiba, Tsutomu
Muto, Manabu
Preclinical Validation of Talaporfin Sodium-Mediated Photodynamic Therapy for Esophageal Squamous Cell Carcinoma
author_facet Ohashi, Shinya
Kikuchi, Osamu
Tsurumaki, Mihoko
Nakai, Yukie
Kasai, Hiroi
Horimatsu, Takahiro
Miyamoto, Shin'ichi
Shimizu, Akira
Chiba, Tsutomu
Muto, Manabu
author_sort Ohashi, Shinya
title Preclinical Validation of Talaporfin Sodium-Mediated Photodynamic Therapy for Esophageal Squamous Cell Carcinoma
title_short Preclinical Validation of Talaporfin Sodium-Mediated Photodynamic Therapy for Esophageal Squamous Cell Carcinoma
title_full Preclinical Validation of Talaporfin Sodium-Mediated Photodynamic Therapy for Esophageal Squamous Cell Carcinoma
title_fullStr Preclinical Validation of Talaporfin Sodium-Mediated Photodynamic Therapy for Esophageal Squamous Cell Carcinoma
title_full_unstemmed Preclinical Validation of Talaporfin Sodium-Mediated Photodynamic Therapy for Esophageal Squamous Cell Carcinoma
title_sort preclinical validation of talaporfin sodium-mediated photodynamic therapy for esophageal squamous cell carcinoma
description Photodynamic therapy (PDT) kills cancer cells via a photochemical reaction mediated by an oncotropic photosensitizer. Herein, we performed an experimental preclinical study to validate the anti-tumour effect of talaporfin sodium-mediated PDT (t-PDT) for esophageal squamous cell carcinoma (ESCC) cells. We used human ESCC cells derived from various differentiation grades or resistant to 5-fluorouracil (5-FU). The cytotoxic effect of t-PDT was determined by evaluating cell viability, apoptosis and generation of reactive oxygen species (ROS) and DNA double-strand breaks. Furthermore, the anti-tumour effect of t-PDT was assessed using an anchorage-independent cell-growth assay and xenograft transplantation models. t-PDT induced potent cytotoxicity in ESCC cells independent of their differentiation grade or 5-FU resistance. Moreover, t-PDT induced robust apoptosis, as indicated by cell shrinkage, perinuclear vacuolization, nuclear fragmentation and induction of annexin V-positive cells. This apoptotic response was accompanied by concurrent activation of ROS, and induction of DNA double-strand breakage. Importantly, t-PDT suppressed efficiently anchorage-independent cell growth as well as ESCC-xenografted tumor formation. In aggregate, t-PDT showed anti-tumor potential for ESCC cells with various histological grades or chemoresistance, providing a novel translational rationale of t-PDT for the treatment of ESCC.
publisher Public Library of Science
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121166/
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