Hematoporphyrin Monomethyl Ether-Mediated Photodynamic Therapy Selectively Kills Sarcomas by Inducing Apoptosis

We investigated the antitumor effect and mechanism of hematoporphyrin monomethyl ether-mediated photodynamic therapy (HMME-PDT) in sarcomas. Intracellular uptake of HMME by osteosarcoma cells (LM8 and K7) was time- and dose-dependent, while this was not observed for myoblast cells (C2C12) and fibrob...

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Main Authors:	Zeng, Hui, Sun, Mengxiong, Zhou, Chenghao, Yin, Fei, Wang, Zhuoying, Hua, Yingqi, Cai, Zhengdong
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3813767/

id	pubmed-3813767
recordtype	oai_dc
spelling	pubmed-38137672013-11-07 Hematoporphyrin Monomethyl Ether-Mediated Photodynamic Therapy Selectively Kills Sarcomas by Inducing Apoptosis Zeng, Hui Sun, Mengxiong Zhou, Chenghao Yin, Fei Wang, Zhuoying Hua, Yingqi Cai, Zhengdong Research Article We investigated the antitumor effect and mechanism of hematoporphyrin monomethyl ether-mediated photodynamic therapy (HMME-PDT) in sarcomas. Intracellular uptake of HMME by osteosarcoma cells (LM8 and K7) was time- and dose-dependent, while this was not observed for myoblast cells (C2C12) and fibroblast cells (NIH/3T3). HMME-PDT markedly inhibited the proliferation of sarcoma cell lines (LM8, MG63, Saos-2, SW1353, TC71, and RD) (P<0.05), and the killing effect was improved with increased HMME concentration and energy intensity. Flow cytometry analysis revealed that LM8, MG63, and Saos-2 cells underwent apoptosis after treatment with HMME-PDT. Additionally, apoptosis was induced after HMME-PDT in a three-dimensional culture of osteosarcoma cells. Hoechst 33342 staining confirmed apoptosis. Cell death caused by PDT was rescued by an irreversible inhibitor (Z-VAD-FMK) of caspase. However, cell viability was not markedly decreased compared with the HMME-PDT group. Expression levels of caspase-1, caspase-3, caspase-6, caspase-9, and poly (ADP-ribose) polymerase (PARP) proteins were markedly up-regulated in the treatment groups and increased with HMME concentration as determined by western blot analysis. In vivo, tumor volume markedly decreased at 7–16 days post-PDT. Hematoxylin and eosin staining revealed widespread necrotic and infiltrative inflammatory cells in the HMME-PDT group. Immunohistochemistry analysis also showed that caspase-1, caspase-3, caspase-6, caspase-9, and PARP proteins were significantly increased in the HMME-PDT group. These results indicate that HMME-PDT has a potent killing effect on osteosarcoma cells in vitro and significantly inhibits tumor growth in vivo, which is associated with the caspase-dependent pathway. Public Library of Science 2013-10-30 /pmc/articles/PMC3813767/ /pubmed/24204937 http://dx.doi.org/10.1371/journal.pone.0077727 Text en © 2013 Zeng 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	Zeng, Hui Sun, Mengxiong Zhou, Chenghao Yin, Fei Wang, Zhuoying Hua, Yingqi Cai, Zhengdong
spellingShingle	Zeng, Hui Sun, Mengxiong Zhou, Chenghao Yin, Fei Wang, Zhuoying Hua, Yingqi Cai, Zhengdong Hematoporphyrin Monomethyl Ether-Mediated Photodynamic Therapy Selectively Kills Sarcomas by Inducing Apoptosis
author_facet	Zeng, Hui Sun, Mengxiong Zhou, Chenghao Yin, Fei Wang, Zhuoying Hua, Yingqi Cai, Zhengdong
author_sort	Zeng, Hui
title	Hematoporphyrin Monomethyl Ether-Mediated Photodynamic Therapy Selectively Kills Sarcomas by Inducing Apoptosis
title_short	Hematoporphyrin Monomethyl Ether-Mediated Photodynamic Therapy Selectively Kills Sarcomas by Inducing Apoptosis
title_full	Hematoporphyrin Monomethyl Ether-Mediated Photodynamic Therapy Selectively Kills Sarcomas by Inducing Apoptosis
title_fullStr	Hematoporphyrin Monomethyl Ether-Mediated Photodynamic Therapy Selectively Kills Sarcomas by Inducing Apoptosis
title_full_unstemmed	Hematoporphyrin Monomethyl Ether-Mediated Photodynamic Therapy Selectively Kills Sarcomas by Inducing Apoptosis
title_sort	hematoporphyrin monomethyl ether-mediated photodynamic therapy selectively kills sarcomas by inducing apoptosis
description	We investigated the antitumor effect and mechanism of hematoporphyrin monomethyl ether-mediated photodynamic therapy (HMME-PDT) in sarcomas. Intracellular uptake of HMME by osteosarcoma cells (LM8 and K7) was time- and dose-dependent, while this was not observed for myoblast cells (C2C12) and fibroblast cells (NIH/3T3). HMME-PDT markedly inhibited the proliferation of sarcoma cell lines (LM8, MG63, Saos-2, SW1353, TC71, and RD) (P<0.05), and the killing effect was improved with increased HMME concentration and energy intensity. Flow cytometry analysis revealed that LM8, MG63, and Saos-2 cells underwent apoptosis after treatment with HMME-PDT. Additionally, apoptosis was induced after HMME-PDT in a three-dimensional culture of osteosarcoma cells. Hoechst 33342 staining confirmed apoptosis. Cell death caused by PDT was rescued by an irreversible inhibitor (Z-VAD-FMK) of caspase. However, cell viability was not markedly decreased compared with the HMME-PDT group. Expression levels of caspase-1, caspase-3, caspase-6, caspase-9, and poly (ADP-ribose) polymerase (PARP) proteins were markedly up-regulated in the treatment groups and increased with HMME concentration as determined by western blot analysis. In vivo, tumor volume markedly decreased at 7–16 days post-PDT. Hematoxylin and eosin staining revealed widespread necrotic and infiltrative inflammatory cells in the HMME-PDT group. Immunohistochemistry analysis also showed that caspase-1, caspase-3, caspase-6, caspase-9, and PARP proteins were significantly increased in the HMME-PDT group. These results indicate that HMME-PDT has a potent killing effect on osteosarcoma cells in vitro and significantly inhibits tumor growth in vivo, which is associated with the caspase-dependent pathway.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3813767/
_version_	1612022173494411264

Hematoporphyrin Monomethyl Ether-Mediated Photodynamic Therapy Selectively Kills Sarcomas by Inducing Apoptosis

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