Sinoporphyrin sodium, a novel sensitizer, triggers mitochondrial-dependent apoptosis in ECA-109 cells via production of reactive oxygen species

Haiping Wang,1 Xiaobing Wang,1 Shaoliang Zhang,2 Pan Wang,1 Kun Zhang,1 Quanhong Liu1 1Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China,...

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Autores principales:	Wang H, Wang X, Zhang S, Wang P, Zhang K, Liu Q
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/031cb543ccd346acaea655d3219d69da
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spelling	oai:doaj.org-article:031cb543ccd346acaea655d3219d69da2021-12-02T07:37:00ZSinoporphyrin sodium, a novel sensitizer, triggers mitochondrial-dependent apoptosis in ECA-109 cells via production of reactive oxygen species1178-2013https://doaj.org/article/031cb543ccd346acaea655d3219d69da2014-06-01T00:00:00Zhttp://www.dovepress.com/sinoporphyrin-sodium-a-novel-sensitizer-triggers-mitochondrial-depende-a17373https://doaj.org/toc/1178-2013 Haiping Wang,1 Xiaobing Wang,1 Shaoliang Zhang,2 Pan Wang,1 Kun Zhang,1 Quanhong Liu1 1Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, 2Qinglong High-Tech Co, Ltd, Yichun, Jiangxi, People's Republic of China Background: Sonodynamic therapy (SDT) is a promising method that uses ultrasound to activate certain chemical sensitizers for the treatment of cancer. The purpose of this study was to investigate the sonoactivity of a novel sensitizer, sinoporphyrin sodium (DVDMS), and its sonotoxicity in an esophageal cancer (ECA-109) cell line. Methods: The fluorescence intensity of DVDMS, hematoporphyrin, protoporphyrin IX, and Photofrin II was detected by fluorescence microscopy and flow cytometry. Generation of singlet oxygen was measured using a 1, 3-diphenylisobenzofuran experiment. A 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay was used to examine cell viability. Production of reactive oxygen species (ROS) and destabilization of the mitochondrial membrane potential were assessed by flow cytometry. Apoptosis was analyzed using Annexin-PE/7-amino-actinomycin D staining. Confocal microscopy was performed to assess mitochondrial damage and identify release of cytochrome C after treatment. Western blots were used to determine expression of oxidative stress-related and apoptosis-associated protein. Ultrastructural changes in the cell were studied by scanning electron microscopy. Results: DVDMS showed higher autofluorescence intensity and singlet oxygen production efficiency compared with other photosensitizers in both cancerous and normal cells. Compared with hematoporphyrin, DVDMS-mediated SDT was more cytotoxic in ECA-109 cells. Abundant intracellular ROS was found in the SDT groups, and the cytotoxicity induced by SDT was effectively remitted by ROS scavengers. DVDMS located mainly to the mitochondria of ECA-109 cells, which were seriously damaged after exposure to SDT. Release of cytochrome C, an increased rate of apoptosis, and activated apoptosis protein were detected in the SDT group. In addition, relatively severe cell damage was observed on scanning electron microscopy after treatment with DVDMS and SDT. Conclusion: These results suggest that DVDMS could be activated by ultrasound, and that DVDMS mediates SDT-induced mitochondrial-dependent apoptosis in ECA-109 cells via production of ROS. Keywords: sonodynamic therapy, sinoporphyrin sodium, reactive oxygen species, mitochondrial damage, apoptosis, ECA-109 cellsWang HWang XZhang SWang PZhang KLiu QDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 3077-3090 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Wang H Wang X Zhang S Wang P Zhang K Liu Q Sinoporphyrin sodium, a novel sensitizer, triggers mitochondrial-dependent apoptosis in ECA-109 cells via production of reactive oxygen species
description	Haiping Wang,1 Xiaobing Wang,1 Shaoliang Zhang,2 Pan Wang,1 Kun Zhang,1 Quanhong Liu1 1Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, 2Qinglong High-Tech Co, Ltd, Yichun, Jiangxi, People's Republic of China Background: Sonodynamic therapy (SDT) is a promising method that uses ultrasound to activate certain chemical sensitizers for the treatment of cancer. The purpose of this study was to investigate the sonoactivity of a novel sensitizer, sinoporphyrin sodium (DVDMS), and its sonotoxicity in an esophageal cancer (ECA-109) cell line. Methods: The fluorescence intensity of DVDMS, hematoporphyrin, protoporphyrin IX, and Photofrin II was detected by fluorescence microscopy and flow cytometry. Generation of singlet oxygen was measured using a 1, 3-diphenylisobenzofuran experiment. A 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay was used to examine cell viability. Production of reactive oxygen species (ROS) and destabilization of the mitochondrial membrane potential were assessed by flow cytometry. Apoptosis was analyzed using Annexin-PE/7-amino-actinomycin D staining. Confocal microscopy was performed to assess mitochondrial damage and identify release of cytochrome C after treatment. Western blots were used to determine expression of oxidative stress-related and apoptosis-associated protein. Ultrastructural changes in the cell were studied by scanning electron microscopy. Results: DVDMS showed higher autofluorescence intensity and singlet oxygen production efficiency compared with other photosensitizers in both cancerous and normal cells. Compared with hematoporphyrin, DVDMS-mediated SDT was more cytotoxic in ECA-109 cells. Abundant intracellular ROS was found in the SDT groups, and the cytotoxicity induced by SDT was effectively remitted by ROS scavengers. DVDMS located mainly to the mitochondria of ECA-109 cells, which were seriously damaged after exposure to SDT. Release of cytochrome C, an increased rate of apoptosis, and activated apoptosis protein were detected in the SDT group. In addition, relatively severe cell damage was observed on scanning electron microscopy after treatment with DVDMS and SDT. Conclusion: These results suggest that DVDMS could be activated by ultrasound, and that DVDMS mediates SDT-induced mitochondrial-dependent apoptosis in ECA-109 cells via production of ROS. Keywords: sonodynamic therapy, sinoporphyrin sodium, reactive oxygen species, mitochondrial damage, apoptosis, ECA-109 cells
format	article
author	Wang H Wang X Zhang S Wang P Zhang K Liu Q
author_facet	Wang H Wang X Zhang S Wang P Zhang K Liu Q
author_sort	Wang H
title	Sinoporphyrin sodium, a novel sensitizer, triggers mitochondrial-dependent apoptosis in ECA-109 cells via production of reactive oxygen species
title_short	Sinoporphyrin sodium, a novel sensitizer, triggers mitochondrial-dependent apoptosis in ECA-109 cells via production of reactive oxygen species
title_full	Sinoporphyrin sodium, a novel sensitizer, triggers mitochondrial-dependent apoptosis in ECA-109 cells via production of reactive oxygen species
title_fullStr	Sinoporphyrin sodium, a novel sensitizer, triggers mitochondrial-dependent apoptosis in ECA-109 cells via production of reactive oxygen species
title_full_unstemmed	Sinoporphyrin sodium, a novel sensitizer, triggers mitochondrial-dependent apoptosis in ECA-109 cells via production of reactive oxygen species
title_sort	sinoporphyrin sodium, a novel sensitizer, triggers mitochondrial-dependent apoptosis in eca-109 cells via production of reactive oxygen species
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/031cb543ccd346acaea655d3219d69da
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Sinoporphyrin sodium, a novel sensitizer, triggers mitochondrial-dependent apoptosis in ECA-109 cells via production of reactive oxygen species

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