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

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...

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Autores principales: Husain, Kazim, Coppola, Domenico, Yang, Chung S., Malafa, Mokenge P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838198/
https://www.ncbi.nlm.nih.gov/pubmed/33500430
http://dx.doi.org/10.1038/s41598-020-80911-z
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author Husain, Kazim
Coppola, Domenico
Yang, Chung S.
Malafa, Mokenge P.
author_facet Husain, Kazim
Coppola, Domenico
Yang, Chung S.
Malafa, Mokenge P.
author_sort Husain, Kazim
collection PubMed
description 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.
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spelling pubmed-78381982021-01-27 Farnesyl dimethyl chromanol targets colon cancer stem cells and prevents colorectal cancer metastasis Husain, Kazim Coppola, Domenico Yang, Chung S. Malafa, Mokenge P. Sci Rep Article 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. Nature Publishing Group UK 2021-01-26 /pmc/articles/PMC7838198/ /pubmed/33500430 http://dx.doi.org/10.1038/s41598-020-80911-z Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Husain, Kazim
Coppola, Domenico
Yang, Chung S.
Malafa, Mokenge P.
Farnesyl dimethyl chromanol targets colon cancer stem cells and prevents colorectal cancer metastasis
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838198/
https://www.ncbi.nlm.nih.gov/pubmed/33500430
http://dx.doi.org/10.1038/s41598-020-80911-z
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