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The combination of lactoferrin and linolenic acid inhibits colorectal tumor growth through activating AMPK/JNK-related apoptosis pathway

Colorectal cancer is a common cause of death with few available therapeutic strategies, and the preventative complexes in adjunctive therapy are urgently needed. Increasing evidences have shown that natural ingredients, including lactoferrin, oleic acid, docosahexaenoic acid (DHA) and linolenic acid...

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Autores principales: Yao, Qianqian, Li, Huiying, Fan, Linlin, Huang, Shengnan, Wang, Jiaqi, Zheng, Nan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174148/
https://www.ncbi.nlm.nih.gov/pubmed/34131514
http://dx.doi.org/10.7717/peerj.11072
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author Yao, Qianqian
Li, Huiying
Fan, Linlin
Huang, Shengnan
Wang, Jiaqi
Zheng, Nan
author_facet Yao, Qianqian
Li, Huiying
Fan, Linlin
Huang, Shengnan
Wang, Jiaqi
Zheng, Nan
author_sort Yao, Qianqian
collection PubMed
description Colorectal cancer is a common cause of death with few available therapeutic strategies, and the preventative complexes in adjunctive therapy are urgently needed. Increasing evidences have shown that natural ingredients, including lactoferrin, oleic acid, docosahexaenoic acid (DHA) and linolenic acid, possess anti-inflammatory and anti-tumor activities. However, investigations and comparisons of their combinations in colorectal tumor model have not been reported, and the mechanism is still unrevealed. In the study, we examined the viability, migration, invasion and apoptosis of HT29 cells to choose the proper doses of these components and to select the effective combination in vitro. BALB/c nude mice bearing colorectal tumor were used to explore the role of selected combination in inhibiting tumor development in vivo. Additionally, metabonomic detection was performed to screen out the specific changed metabolitesand related pathway. The results demonstrated that lactoferrin at 6.25 μM, oleic acid at 0.18 mM, DHA at 0.18 mM, and linolenic acid at 0.15 mM significantly inhibited the viabilities of HT29 cells (p < 0.05). The combination of lactoferrin (6.25 μM) + linolenic acid (0.15 mM) exhibited the strongest activity in inhibiting the migration and invasion of HT29 cells in vivo and suppressing tumor development in vitro (p < 0.05). Furthermore, the lactoferrin + linolenic acid combination activated p-AMPK and p-JNK, thereby inducing apoptosis of HT29 cells (p < 0.05). The present study was the first to show that lactoferrin + linolenic acid combination inhibited HT29 tumor formation by activating AMPK/JNK related pathway.
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spelling pubmed-81741482021-06-14 The combination of lactoferrin and linolenic acid inhibits colorectal tumor growth through activating AMPK/JNK-related apoptosis pathway Yao, Qianqian Li, Huiying Fan, Linlin Huang, Shengnan Wang, Jiaqi Zheng, Nan PeerJ Cell Biology Colorectal cancer is a common cause of death with few available therapeutic strategies, and the preventative complexes in adjunctive therapy are urgently needed. Increasing evidences have shown that natural ingredients, including lactoferrin, oleic acid, docosahexaenoic acid (DHA) and linolenic acid, possess anti-inflammatory and anti-tumor activities. However, investigations and comparisons of their combinations in colorectal tumor model have not been reported, and the mechanism is still unrevealed. In the study, we examined the viability, migration, invasion and apoptosis of HT29 cells to choose the proper doses of these components and to select the effective combination in vitro. BALB/c nude mice bearing colorectal tumor were used to explore the role of selected combination in inhibiting tumor development in vivo. Additionally, metabonomic detection was performed to screen out the specific changed metabolitesand related pathway. The results demonstrated that lactoferrin at 6.25 μM, oleic acid at 0.18 mM, DHA at 0.18 mM, and linolenic acid at 0.15 mM significantly inhibited the viabilities of HT29 cells (p < 0.05). The combination of lactoferrin (6.25 μM) + linolenic acid (0.15 mM) exhibited the strongest activity in inhibiting the migration and invasion of HT29 cells in vivo and suppressing tumor development in vitro (p < 0.05). Furthermore, the lactoferrin + linolenic acid combination activated p-AMPK and p-JNK, thereby inducing apoptosis of HT29 cells (p < 0.05). The present study was the first to show that lactoferrin + linolenic acid combination inhibited HT29 tumor formation by activating AMPK/JNK related pathway. PeerJ Inc. 2021-05-31 /pmc/articles/PMC8174148/ /pubmed/34131514 http://dx.doi.org/10.7717/peerj.11072 Text en © 2021 Yao et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Cell Biology
Yao, Qianqian
Li, Huiying
Fan, Linlin
Huang, Shengnan
Wang, Jiaqi
Zheng, Nan
The combination of lactoferrin and linolenic acid inhibits colorectal tumor growth through activating AMPK/JNK-related apoptosis pathway
title The combination of lactoferrin and linolenic acid inhibits colorectal tumor growth through activating AMPK/JNK-related apoptosis pathway
title_full The combination of lactoferrin and linolenic acid inhibits colorectal tumor growth through activating AMPK/JNK-related apoptosis pathway
title_fullStr The combination of lactoferrin and linolenic acid inhibits colorectal tumor growth through activating AMPK/JNK-related apoptosis pathway
title_full_unstemmed The combination of lactoferrin and linolenic acid inhibits colorectal tumor growth through activating AMPK/JNK-related apoptosis pathway
title_short The combination of lactoferrin and linolenic acid inhibits colorectal tumor growth through activating AMPK/JNK-related apoptosis pathway
title_sort combination of lactoferrin and linolenic acid inhibits colorectal tumor growth through activating ampk/jnk-related apoptosis pathway
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174148/
https://www.ncbi.nlm.nih.gov/pubmed/34131514
http://dx.doi.org/10.7717/peerj.11072
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