PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma

Abstract Recurrence following chemotherapy is observed in the majority of patients with pancreatic ductal adenocarcinoma (PDAC). Recent studies suggest that cancer stem cells (CSCs) may be involved in PDAC recurrence and metastasis. However, an efficient approach to targeting pancreatic CSCs remains...

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Autores principales:	Motofumi Kumazoe, Mika Takai, Shun Hiroi, Chieri Takeuchi, Maasa Yamanouchi, Takashi Nojiri, Hiroaki Onda, Jaehoon Bae, Yuhui Huang, Kanako Takamatsu, Shuya Yamashita, Shuhei Yamada, Kenji Kangawa, Takashi Takahashi, Hiroshi Tanaka, Hirofumi Tachibana
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dfa898deffc744c9b00b298fc75a504e
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spelling	oai:doaj.org-article:dfa898deffc744c9b00b298fc75a504e2021-12-02T12:32:50ZPDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma10.1038/s41598-017-02162-92045-2322https://doaj.org/article/dfa898deffc744c9b00b298fc75a504e2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02162-9https://doaj.org/toc/2045-2322Abstract Recurrence following chemotherapy is observed in the majority of patients with pancreatic ductal adenocarcinoma (PDAC). Recent studies suggest that cancer stem cells (CSCs) may be involved in PDAC recurrence and metastasis. However, an efficient approach to targeting pancreatic CSCs remains to be established. Here we show that in cancer cells overexpressing the 67-kDa laminin receptor (67LR)-dependent cyclic GMP (cGMP) inducer, epigallocatechin-3-O-gallate (EGCG) and a phosphodiesterase 3 (PDE3) inhibitor in combination significantly suppressed the Forkhead box O3 and CD44 axis, which is indispensable for the CSC properties of PDAC. We confirmed that the EGCG and PDE3 inhibitor in combination strongly suppressed tumour formation and liver metastasis in vivo. We also found that a synthesized EGCG analog capable of inducing strong cGMP production drastically suppressed the CSC properties of PDAC and extended the survival period in vivo. In conclusion, the combination treatment of EGCG and a PDE3 inhibitor as a strong cGMP inducer could be a potential treatment candidate for the eradication of CSCs of PDAC.Motofumi KumazoeMika TakaiShun HiroiChieri TakeuchiMaasa YamanouchiTakashi NojiriHiroaki OndaJaehoon BaeYuhui HuangKanako TakamatsuShuya YamashitaShuhei YamadaKenji KangawaTakashi TakahashiHiroshi TanakaHirofumi TachibanaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Motofumi Kumazoe Mika Takai Shun Hiroi Chieri Takeuchi Maasa Yamanouchi Takashi Nojiri Hiroaki Onda Jaehoon Bae Yuhui Huang Kanako Takamatsu Shuya Yamashita Shuhei Yamada Kenji Kangawa Takashi Takahashi Hiroshi Tanaka Hirofumi Tachibana PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma
description	Abstract Recurrence following chemotherapy is observed in the majority of patients with pancreatic ductal adenocarcinoma (PDAC). Recent studies suggest that cancer stem cells (CSCs) may be involved in PDAC recurrence and metastasis. However, an efficient approach to targeting pancreatic CSCs remains to be established. Here we show that in cancer cells overexpressing the 67-kDa laminin receptor (67LR)-dependent cyclic GMP (cGMP) inducer, epigallocatechin-3-O-gallate (EGCG) and a phosphodiesterase 3 (PDE3) inhibitor in combination significantly suppressed the Forkhead box O3 and CD44 axis, which is indispensable for the CSC properties of PDAC. We confirmed that the EGCG and PDE3 inhibitor in combination strongly suppressed tumour formation and liver metastasis in vivo. We also found that a synthesized EGCG analog capable of inducing strong cGMP production drastically suppressed the CSC properties of PDAC and extended the survival period in vivo. In conclusion, the combination treatment of EGCG and a PDE3 inhibitor as a strong cGMP inducer could be a potential treatment candidate for the eradication of CSCs of PDAC.
format	article
author	Motofumi Kumazoe Mika Takai Shun Hiroi Chieri Takeuchi Maasa Yamanouchi Takashi Nojiri Hiroaki Onda Jaehoon Bae Yuhui Huang Kanako Takamatsu Shuya Yamashita Shuhei Yamada Kenji Kangawa Takashi Takahashi Hiroshi Tanaka Hirofumi Tachibana
author_facet	Motofumi Kumazoe Mika Takai Shun Hiroi Chieri Takeuchi Maasa Yamanouchi Takashi Nojiri Hiroaki Onda Jaehoon Bae Yuhui Huang Kanako Takamatsu Shuya Yamashita Shuhei Yamada Kenji Kangawa Takashi Takahashi Hiroshi Tanaka Hirofumi Tachibana
author_sort	Motofumi Kumazoe
title	PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma
title_short	PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma
title_full	PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma
title_fullStr	PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma
title_full_unstemmed	PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma
title_sort	pde3 inhibitor and egcg combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/dfa898deffc744c9b00b298fc75a504e
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PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma

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