Farnesyl dimethyl chromanol targets colon cancer stem cells and prevents colorectal cancer metastasis

Abstract The activation and growth of tumour-initiating cells with stem-like properties in distant organs characterize colorectal cancer (CRC) growth and metastasis. Thus, inhibition of colon cancer stem cell (CCSC) growth holds promise for CRC growth and metastasis prevention. We and others have sh...

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Autores principales:	Kazim Husain, Domenico Coppola, Chung S. Yang, Mokenge P. Malafa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/48038e2a84504fb88f55ecb9c9524bbc
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spelling	oai:doaj.org-article:48038e2a84504fb88f55ecb9c9524bbc2021-12-02T10:47:54ZFarnesyl dimethyl chromanol targets colon cancer stem cells and prevents colorectal cancer metastasis10.1038/s41598-020-80911-z2045-2322https://doaj.org/article/48038e2a84504fb88f55ecb9c9524bbc2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80911-zhttps://doaj.org/toc/2045-2322Abstract The activation and growth of tumour-initiating cells with stem-like properties in distant organs characterize colorectal cancer (CRC) growth and metastasis. Thus, inhibition of colon cancer stem cell (CCSC) growth holds promise for CRC growth and metastasis prevention. We and others have shown that farnesyl dimethyl chromanol (FDMC) inhibits cancer cell growth and induces apoptosis in vitro and in vivo. We provide the first demonstration that FDMC inhibits CCSC viability, survival, self-renewal (spheroid formation), pluripotent transcription factors (Nanog, Oct4, and Sox2) expression, organoids formation, and Wnt/β-catenin signalling, as evidenced by comparisons with vehicle-treated controls. In addition, FDMC inhibits CCSC migration, invasion, inflammation (NF-kB), angiogenesis (vascular endothelial growth factor, VEGF), and metastasis (MMP9), which are critical tumour metastasis processes. Moreover, FDMC induced apoptosis (TUNEL, Annexin V, cleaved caspase 3, and cleaved PARP) in CCSCs and CCSC-derived spheroids and organoids. Finally, in an orthotopic (cecum-injected CCSCs) xenograft metastasis model, we show that FDMC significantly retards CCSC-derived tumour growth (Ki-67); inhibits inflammation (NF-kB), angiogenesis (VEGF and CD31), and β-catenin signalling; and induces apoptosis (cleaved PARP) in tumour tissues and inhibits liver metastasis. In summary, our results demonstrate that FDMC inhibits the CCSC metastatic phenotype and thereby supports investigating its ability to prevent CRC metastases.Kazim HusainDomenico CoppolaChung S. YangMokenge P. MalafaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kazim Husain Domenico Coppola Chung S. Yang Mokenge P. Malafa Farnesyl dimethyl chromanol targets colon cancer stem cells and prevents colorectal cancer metastasis
description	Abstract The activation and growth of tumour-initiating cells with stem-like properties in distant organs characterize colorectal cancer (CRC) growth and metastasis. Thus, inhibition of colon cancer stem cell (CCSC) growth holds promise for CRC growth and metastasis prevention. We and others have shown that farnesyl dimethyl chromanol (FDMC) inhibits cancer cell growth and induces apoptosis in vitro and in vivo. We provide the first demonstration that FDMC inhibits CCSC viability, survival, self-renewal (spheroid formation), pluripotent transcription factors (Nanog, Oct4, and Sox2) expression, organoids formation, and Wnt/β-catenin signalling, as evidenced by comparisons with vehicle-treated controls. In addition, FDMC inhibits CCSC migration, invasion, inflammation (NF-kB), angiogenesis (vascular endothelial growth factor, VEGF), and metastasis (MMP9), which are critical tumour metastasis processes. Moreover, FDMC induced apoptosis (TUNEL, Annexin V, cleaved caspase 3, and cleaved PARP) in CCSCs and CCSC-derived spheroids and organoids. Finally, in an orthotopic (cecum-injected CCSCs) xenograft metastasis model, we show that FDMC significantly retards CCSC-derived tumour growth (Ki-67); inhibits inflammation (NF-kB), angiogenesis (VEGF and CD31), and β-catenin signalling; and induces apoptosis (cleaved PARP) in tumour tissues and inhibits liver metastasis. In summary, our results demonstrate that FDMC inhibits the CCSC metastatic phenotype and thereby supports investigating its ability to prevent CRC metastases.
format	article
author	Kazim Husain Domenico Coppola Chung S. Yang Mokenge P. Malafa
author_facet	Kazim Husain Domenico Coppola Chung S. Yang Mokenge P. Malafa
author_sort	Kazim Husain
title	Farnesyl dimethyl chromanol targets colon cancer stem cells and prevents colorectal cancer metastasis
title_short	Farnesyl dimethyl chromanol targets colon cancer stem cells and prevents colorectal cancer metastasis
title_full	Farnesyl dimethyl chromanol targets colon cancer stem cells and prevents colorectal cancer metastasis
title_fullStr	Farnesyl dimethyl chromanol targets colon cancer stem cells and prevents colorectal cancer metastasis
title_full_unstemmed	Farnesyl dimethyl chromanol targets colon cancer stem cells and prevents colorectal cancer metastasis
title_sort	farnesyl dimethyl chromanol targets colon cancer stem cells and prevents colorectal cancer metastasis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/48038e2a84504fb88f55ecb9c9524bbc
work_keys_str_mv	AT kazimhusain farnesyldimethylchromanoltargetscoloncancerstemcellsandpreventscolorectalcancermetastasis AT domenicocoppola farnesyldimethylchromanoltargetscoloncancerstemcellsandpreventscolorectalcancermetastasis AT chungsyang farnesyldimethylchromanoltargetscoloncancerstemcellsandpreventscolorectalcancermetastasis AT mokengepmalafa farnesyldimethylchromanoltargetscoloncancerstemcellsandpreventscolorectalcancermetastasis
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Farnesyl dimethyl chromanol targets colon cancer stem cells and prevents colorectal cancer metastasis

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