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Functional modification of adipocytes by grape seed extract impairs their pro-tumorigenic signaling on colon cancer stem cells and the daughter cancer cells
With global rise in obesity, it is imperative that we identify obesity-driven factors that increase growth and progression of colorectal cancer (CRC), and also discover and develop agents with anti-CRC efficacy under obese conditions. Here in, we investigated grape seed extract (GSE), a well-defined...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259412/ https://www.ncbi.nlm.nih.gov/pubmed/25294814 |
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author | Kumar, Sushil Kumar, Dileep Raina, Komal Agarwal, Rajesh Agarwal, Chapla |
author_facet | Kumar, Sushil Kumar, Dileep Raina, Komal Agarwal, Rajesh Agarwal, Chapla |
author_sort | Kumar, Sushil |
collection | PubMed |
description | With global rise in obesity, it is imperative that we identify obesity-driven factors that increase growth and progression of colorectal cancer (CRC), and also discover and develop agents with anti-CRC efficacy under obese conditions. Here in, we investigated grape seed extract (GSE), a well-defined agent with both preventive and anti-CRC efficacy, for its potential to impair pro-tumorigenic signaling of adipocytes on CRC/colon cancer stem cells (CSCs) and associated molecular mechanisms, to control CRC under obese conditions. GSE treatment significantly decreased the growth and invasion promoting effects of both mouse and human adipocytes on CRC cells. Moreover, GSE exerted a direct inhibitory effect, as well as it strongly reduced the growth promoting signals of adipocytes, on colon CSCs. These GSE effects were associated with a decrease in both mRNA and protein levels of various CSC-associated molecules. Notably, GSE effects on adipocytes were not due to changes in lipid content, but by inducing the ‘browning’ of adipocytes as evidenced by an increase in UCP-1 mRNA level and mitochondriogenesis. Together, these findings, for the first time, suggest the ability of GSE to induce ‘brown remodeling’ of white adipocytes, which causes functional modification of adipocytes thus impairing their pro-tumorigenic signals on colon CSCs/CRC cells. |
format | Online Article Text |
id | pubmed-4259412 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-42594122014-12-10 Functional modification of adipocytes by grape seed extract impairs their pro-tumorigenic signaling on colon cancer stem cells and the daughter cancer cells Kumar, Sushil Kumar, Dileep Raina, Komal Agarwal, Rajesh Agarwal, Chapla Oncotarget Research Paper With global rise in obesity, it is imperative that we identify obesity-driven factors that increase growth and progression of colorectal cancer (CRC), and also discover and develop agents with anti-CRC efficacy under obese conditions. Here in, we investigated grape seed extract (GSE), a well-defined agent with both preventive and anti-CRC efficacy, for its potential to impair pro-tumorigenic signaling of adipocytes on CRC/colon cancer stem cells (CSCs) and associated molecular mechanisms, to control CRC under obese conditions. GSE treatment significantly decreased the growth and invasion promoting effects of both mouse and human adipocytes on CRC cells. Moreover, GSE exerted a direct inhibitory effect, as well as it strongly reduced the growth promoting signals of adipocytes, on colon CSCs. These GSE effects were associated with a decrease in both mRNA and protein levels of various CSC-associated molecules. Notably, GSE effects on adipocytes were not due to changes in lipid content, but by inducing the ‘browning’ of adipocytes as evidenced by an increase in UCP-1 mRNA level and mitochondriogenesis. Together, these findings, for the first time, suggest the ability of GSE to induce ‘brown remodeling’ of white adipocytes, which causes functional modification of adipocytes thus impairing their pro-tumorigenic signals on colon CSCs/CRC cells. Impact Journals LLC 2014-10-10 /pmc/articles/PMC4259412/ /pubmed/25294814 Text en Copyright: © 2014 Kumar et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
spellingShingle | Research Paper Kumar, Sushil Kumar, Dileep Raina, Komal Agarwal, Rajesh Agarwal, Chapla Functional modification of adipocytes by grape seed extract impairs their pro-tumorigenic signaling on colon cancer stem cells and the daughter cancer cells |
title | Functional modification of adipocytes by grape seed extract impairs their pro-tumorigenic signaling on colon cancer stem cells and the daughter cancer cells |
title_full | Functional modification of adipocytes by grape seed extract impairs their pro-tumorigenic signaling on colon cancer stem cells and the daughter cancer cells |
title_fullStr | Functional modification of adipocytes by grape seed extract impairs their pro-tumorigenic signaling on colon cancer stem cells and the daughter cancer cells |
title_full_unstemmed | Functional modification of adipocytes by grape seed extract impairs their pro-tumorigenic signaling on colon cancer stem cells and the daughter cancer cells |
title_short | Functional modification of adipocytes by grape seed extract impairs their pro-tumorigenic signaling on colon cancer stem cells and the daughter cancer cells |
title_sort | functional modification of adipocytes by grape seed extract impairs their pro-tumorigenic signaling on colon cancer stem cells and the daughter cancer cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259412/ https://www.ncbi.nlm.nih.gov/pubmed/25294814 |
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