Transcutaneous carbon dioxide induces mitochondrial apoptosis and suppresses metastasis of oral squamous cell carcinoma in vivo.

Squamous cell carcinoma (SCC) is the main histological type of oral cancer. Its growth rate and incidence of metastasis to regional lymph nodes is influenced by various factors, including hypoxic conditions. We have previously reported that transcutaneous CO2 induces mitochondrial apoptosis and decr...

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Autores principales:	Daisuke Takeda, Takumi Hasegawa, Takeshi Ueha, Yusuke Imai, Akiko Sakakibara, Masaya Minoda, Teruya Kawamoto, Tsutomu Minamikawa, Yasuyuki Shibuya, Toshihiro Akisue, Yoshitada Sakai, Masahiro Kurosaka, Takahide Komori
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/44e484aed98544f1bc53627bb1d34f8c
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spelling	oai:doaj.org-article:44e484aed98544f1bc53627bb1d34f8c2021-11-25T06:09:56ZTranscutaneous carbon dioxide induces mitochondrial apoptosis and suppresses metastasis of oral squamous cell carcinoma in vivo.1932-620310.1371/journal.pone.0100530https://doaj.org/article/44e484aed98544f1bc53627bb1d34f8c2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24988190/?tool=EBIhttps://doaj.org/toc/1932-6203Squamous cell carcinoma (SCC) is the main histological type of oral cancer. Its growth rate and incidence of metastasis to regional lymph nodes is influenced by various factors, including hypoxic conditions. We have previously reported that transcutaneous CO2 induces mitochondrial apoptosis and decreases lung metastasis by reoxygenating sarcoma cells. However, previous studies have not determined the sequential mechanism by which transcutaneous CO2 suppresses growth of epithelial tumors, including SCCs. Moreover, there is no report that transcutaneous CO2 suppresses lymphogenous metastasis using human cell lines xenografts. In this study, we examined the effects of transcutaneous CO2 on cancer apoptosis and lymphogenous metastasis using human SCC xenografts. Our results showed that transcutaneous CO2 affects expressions of PGC-1α and TFAM and protein levels of cleavage products of caspase-3, caspase-9 and PARP, which relatives mitochondrial apoptosis. They also showed that transcutaneous CO2 significantly inhibits SCC tumor growth and affects expressions of HIF-1α, VEGF, MMP-2 and MMP-9, which play essential roles in tumor angiogenesis, invasion and metastasis. In conclusion, transcutaneous CO2 suppressed tumor growth, increased mitochondrial apoptosis and decreased the number of lymph node metastasis in human SCC by decreasing intra-tumoral hypoxia and suppressing metastatic potential with no observable effect in vivo. Our findings indicate that transcutaneous CO2 could be a novel therapeutic tool for treating human SCC.Daisuke TakedaTakumi HasegawaTakeshi UehaYusuke ImaiAkiko SakakibaraMasaya MinodaTeruya KawamotoTsutomu MinamikawaYasuyuki ShibuyaToshihiro AkisueYoshitada SakaiMasahiro KurosakaTakahide KomoriPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e100530 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daisuke Takeda Takumi Hasegawa Takeshi Ueha Yusuke Imai Akiko Sakakibara Masaya Minoda Teruya Kawamoto Tsutomu Minamikawa Yasuyuki Shibuya Toshihiro Akisue Yoshitada Sakai Masahiro Kurosaka Takahide Komori Transcutaneous carbon dioxide induces mitochondrial apoptosis and suppresses metastasis of oral squamous cell carcinoma in vivo.
description	Squamous cell carcinoma (SCC) is the main histological type of oral cancer. Its growth rate and incidence of metastasis to regional lymph nodes is influenced by various factors, including hypoxic conditions. We have previously reported that transcutaneous CO2 induces mitochondrial apoptosis and decreases lung metastasis by reoxygenating sarcoma cells. However, previous studies have not determined the sequential mechanism by which transcutaneous CO2 suppresses growth of epithelial tumors, including SCCs. Moreover, there is no report that transcutaneous CO2 suppresses lymphogenous metastasis using human cell lines xenografts. In this study, we examined the effects of transcutaneous CO2 on cancer apoptosis and lymphogenous metastasis using human SCC xenografts. Our results showed that transcutaneous CO2 affects expressions of PGC-1α and TFAM and protein levels of cleavage products of caspase-3, caspase-9 and PARP, which relatives mitochondrial apoptosis. They also showed that transcutaneous CO2 significantly inhibits SCC tumor growth and affects expressions of HIF-1α, VEGF, MMP-2 and MMP-9, which play essential roles in tumor angiogenesis, invasion and metastasis. In conclusion, transcutaneous CO2 suppressed tumor growth, increased mitochondrial apoptosis and decreased the number of lymph node metastasis in human SCC by decreasing intra-tumoral hypoxia and suppressing metastatic potential with no observable effect in vivo. Our findings indicate that transcutaneous CO2 could be a novel therapeutic tool for treating human SCC.
format	article
author	Daisuke Takeda Takumi Hasegawa Takeshi Ueha Yusuke Imai Akiko Sakakibara Masaya Minoda Teruya Kawamoto Tsutomu Minamikawa Yasuyuki Shibuya Toshihiro Akisue Yoshitada Sakai Masahiro Kurosaka Takahide Komori
author_facet	Daisuke Takeda Takumi Hasegawa Takeshi Ueha Yusuke Imai Akiko Sakakibara Masaya Minoda Teruya Kawamoto Tsutomu Minamikawa Yasuyuki Shibuya Toshihiro Akisue Yoshitada Sakai Masahiro Kurosaka Takahide Komori
author_sort	Daisuke Takeda
title	Transcutaneous carbon dioxide induces mitochondrial apoptosis and suppresses metastasis of oral squamous cell carcinoma in vivo.
title_short	Transcutaneous carbon dioxide induces mitochondrial apoptosis and suppresses metastasis of oral squamous cell carcinoma in vivo.
title_full	Transcutaneous carbon dioxide induces mitochondrial apoptosis and suppresses metastasis of oral squamous cell carcinoma in vivo.
title_fullStr	Transcutaneous carbon dioxide induces mitochondrial apoptosis and suppresses metastasis of oral squamous cell carcinoma in vivo.
title_full_unstemmed	Transcutaneous carbon dioxide induces mitochondrial apoptosis and suppresses metastasis of oral squamous cell carcinoma in vivo.
title_sort	transcutaneous carbon dioxide induces mitochondrial apoptosis and suppresses metastasis of oral squamous cell carcinoma in vivo.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/44e484aed98544f1bc53627bb1d34f8c
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Transcutaneous carbon dioxide induces mitochondrial apoptosis and suppresses metastasis of oral squamous cell carcinoma in vivo.

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