CD44/CD133-Positive Colorectal Cancer Stem Cells are Sensitive to Trifluridine Exposure

Abstract Cancer stem cells (CSCs) are involved in metastatic colorectal cancer recurrence, but no effective therapy targeting these cells is currently available. Because trifluridine (FTD)/tipiracil therapy is used for refractory colorectal cancer, we sought to determine whether FTD is effective aga...

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Autores principales:	Kenta Tsunekuni, Masamitsu Konno, Naotsugu Haraguchi, Jun Koseki, Ayumu Asai, Kazuaki Matsuoka, Takashi Kobunai, Teiji Takechi, Yuichiro Doki, Masaki Mori, Hideshi Ishii
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/57752e7b4a7f4f24852730100fc831b5
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spelling	oai:doaj.org-article:57752e7b4a7f4f24852730100fc831b52021-12-02T16:08:28ZCD44/CD133-Positive Colorectal Cancer Stem Cells are Sensitive to Trifluridine Exposure10.1038/s41598-019-50968-62045-2322https://doaj.org/article/57752e7b4a7f4f24852730100fc831b52019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-50968-6https://doaj.org/toc/2045-2322Abstract Cancer stem cells (CSCs) are involved in metastatic colorectal cancer recurrence, but no effective therapy targeting these cells is currently available. Because trifluridine (FTD)/tipiracil therapy is used for refractory colorectal cancer, we sought to determine whether FTD is effective against CSC-like cells. CD44+CD133+ high-expressing and other populations of human DLD-1 colon cancer cells were separately isolated through fluorescence-activated cell sorting. The sphere-forming activity of each population and the anti-sphere-forming effects of FTD and fluorouracil (5-FU) on CD44+CD133+ cells were then measured. CD44+CD133+ DLD-1 cells formed substantially more spheres than other cells. Moreover, treating CD44+CD133+ DLD-1 cells with subtoxic concentrations of FTD (1 µM) inhibited sphere formation, and this was superior to the effect of subtoxic concentrations (1 µM) of 5-FU. The associated inhibition rates for FTD and 5-FU were 58.2% and 26.1%, respectively. Further, CD44+CD133+ DLD-1 cells expressed higher levels of thymidine kinase 1, which is responsible for FTD phosphorylation, than DLD-1 cells, and FTD was incorporated into the DNA of CD44+CD133+ DLD-1 cells. Thus, our data show that FTD treatment is effective against CSC-like cells and might be applied as CSC-targeting chemotherapy for tumor subtypes with high CD44 and CD133 expression.Kenta TsunekuniMasamitsu KonnoNaotsugu HaraguchiJun KosekiAyumu AsaiKazuaki MatsuokaTakashi KobunaiTeiji TakechiYuichiro DokiMasaki MoriHideshi IshiiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-8 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kenta Tsunekuni Masamitsu Konno Naotsugu Haraguchi Jun Koseki Ayumu Asai Kazuaki Matsuoka Takashi Kobunai Teiji Takechi Yuichiro Doki Masaki Mori Hideshi Ishii CD44/CD133-Positive Colorectal Cancer Stem Cells are Sensitive to Trifluridine Exposure
description	Abstract Cancer stem cells (CSCs) are involved in metastatic colorectal cancer recurrence, but no effective therapy targeting these cells is currently available. Because trifluridine (FTD)/tipiracil therapy is used for refractory colorectal cancer, we sought to determine whether FTD is effective against CSC-like cells. CD44+CD133+ high-expressing and other populations of human DLD-1 colon cancer cells were separately isolated through fluorescence-activated cell sorting. The sphere-forming activity of each population and the anti-sphere-forming effects of FTD and fluorouracil (5-FU) on CD44+CD133+ cells were then measured. CD44+CD133+ DLD-1 cells formed substantially more spheres than other cells. Moreover, treating CD44+CD133+ DLD-1 cells with subtoxic concentrations of FTD (1 µM) inhibited sphere formation, and this was superior to the effect of subtoxic concentrations (1 µM) of 5-FU. The associated inhibition rates for FTD and 5-FU were 58.2% and 26.1%, respectively. Further, CD44+CD133+ DLD-1 cells expressed higher levels of thymidine kinase 1, which is responsible for FTD phosphorylation, than DLD-1 cells, and FTD was incorporated into the DNA of CD44+CD133+ DLD-1 cells. Thus, our data show that FTD treatment is effective against CSC-like cells and might be applied as CSC-targeting chemotherapy for tumor subtypes with high CD44 and CD133 expression.
format	article
author	Kenta Tsunekuni Masamitsu Konno Naotsugu Haraguchi Jun Koseki Ayumu Asai Kazuaki Matsuoka Takashi Kobunai Teiji Takechi Yuichiro Doki Masaki Mori Hideshi Ishii
author_facet	Kenta Tsunekuni Masamitsu Konno Naotsugu Haraguchi Jun Koseki Ayumu Asai Kazuaki Matsuoka Takashi Kobunai Teiji Takechi Yuichiro Doki Masaki Mori Hideshi Ishii
author_sort	Kenta Tsunekuni
title	CD44/CD133-Positive Colorectal Cancer Stem Cells are Sensitive to Trifluridine Exposure
title_short	CD44/CD133-Positive Colorectal Cancer Stem Cells are Sensitive to Trifluridine Exposure
title_full	CD44/CD133-Positive Colorectal Cancer Stem Cells are Sensitive to Trifluridine Exposure
title_fullStr	CD44/CD133-Positive Colorectal Cancer Stem Cells are Sensitive to Trifluridine Exposure
title_full_unstemmed	CD44/CD133-Positive Colorectal Cancer Stem Cells are Sensitive to Trifluridine Exposure
title_sort	cd44/cd133-positive colorectal cancer stem cells are sensitive to trifluridine exposure
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/57752e7b4a7f4f24852730100fc831b5
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_version_	1718384469413462016

CD44/CD133-Positive Colorectal Cancer Stem Cells are Sensitive to Trifluridine Exposure

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