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Krill oil extract inhibits the migration of human colorectal cancer cells and down-regulates EGFR signalling and PD-L1 expression

BACKGROUND: The currently available treatments for colorectal cancer (CRC) are often associated with serious side-effects. Therefore, the development of a novel nutraceutical agent may provide an alternative complementary therapy for CRC. Overexpression of the epidermal growth factor receptor (EGFR)...

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Autores principales: Jayathilake, Abilasha G., Veale, Margaret F., Luwor, Rodney Brain, Nurgali, Kulmira, Su, Xiao Q.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720407/
https://www.ncbi.nlm.nih.gov/pubmed/33287803
http://dx.doi.org/10.1186/s12906-020-03160-7
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author Jayathilake, Abilasha G.
Veale, Margaret F.
Luwor, Rodney Brain
Nurgali, Kulmira
Su, Xiao Q.
author_facet Jayathilake, Abilasha G.
Veale, Margaret F.
Luwor, Rodney Brain
Nurgali, Kulmira
Su, Xiao Q.
author_sort Jayathilake, Abilasha G.
collection PubMed
description BACKGROUND: The currently available treatments for colorectal cancer (CRC) are often associated with serious side-effects. Therefore, the development of a novel nutraceutical agent may provide an alternative complementary therapy for CRC. Overexpression of the epidermal growth factor receptor (EGFR) associates with a range of cancers while downregulation of EGFR signalling can inhibit cancer growth. Our previous studies have shown that the free fatty acid extract (FFAE) of krill oil exhibits anti-proliferative and pro-apoptotic properties. This study determines the effects of krill oil extract on the migration of human CRC cells, and its potential role in modulating EGFR signalling pathway and the expression of programmed death ligand 1 (PD-L1). METHODS: Human CRC cells, DLD-1 and HT-29 were treated with FFAE of KO at 0.03 and 0.12 μL/100 μL for 8 or 24 h. Cell migration was determined by Boyden chamber migration assay. The expression of EGFR, phosphorylated EGFR (pEGFR), protein kinase B (AKT), phosphorylated AKT (pAKT), extracellular signal regulated kinase (ERK1/2), phosphorylated ERK1/2 (pERK1/2) as well as PD-L1 were assessed by western blotting and immunohistochemistry. RESULTS: The FFAE of krill oil significantly inhibited cell migration compared to ethanol-treated (vehicle control) cells (P < 0.01 to P < 0.001). At the molecular level, krill oil extract reduced the expression of EGFR, pEGFR (P < 0.001 for both) and their downstream signalling, pERK1/2 and pAKT (P < 0.01 to P < 0.001) without altering total ERK 1/2 and AKT levels. In addition, the expression of PD-L1 was reduced by 67 to 72% (P < 0.001) following the treatment with krill oil extract. CONCLUSION: This study has demonstrated that krill oil may be a potential therapeutic/adjunctive agent for CRC attributed to its anti-migratory effects.. The potential anti-cancer properties of krill oil are likely to be associated with the downregulation of EGFR, pEGFR and their downstream pERK/ERK1/2 and pAKT/AKT signalling pathways along with the downregulation of PD-L1.
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spelling pubmed-77204072020-12-07 Krill oil extract inhibits the migration of human colorectal cancer cells and down-regulates EGFR signalling and PD-L1 expression Jayathilake, Abilasha G. Veale, Margaret F. Luwor, Rodney Brain Nurgali, Kulmira Su, Xiao Q. BMC Complement Med Ther Research Article BACKGROUND: The currently available treatments for colorectal cancer (CRC) are often associated with serious side-effects. Therefore, the development of a novel nutraceutical agent may provide an alternative complementary therapy for CRC. Overexpression of the epidermal growth factor receptor (EGFR) associates with a range of cancers while downregulation of EGFR signalling can inhibit cancer growth. Our previous studies have shown that the free fatty acid extract (FFAE) of krill oil exhibits anti-proliferative and pro-apoptotic properties. This study determines the effects of krill oil extract on the migration of human CRC cells, and its potential role in modulating EGFR signalling pathway and the expression of programmed death ligand 1 (PD-L1). METHODS: Human CRC cells, DLD-1 and HT-29 were treated with FFAE of KO at 0.03 and 0.12 μL/100 μL for 8 or 24 h. Cell migration was determined by Boyden chamber migration assay. The expression of EGFR, phosphorylated EGFR (pEGFR), protein kinase B (AKT), phosphorylated AKT (pAKT), extracellular signal regulated kinase (ERK1/2), phosphorylated ERK1/2 (pERK1/2) as well as PD-L1 were assessed by western blotting and immunohistochemistry. RESULTS: The FFAE of krill oil significantly inhibited cell migration compared to ethanol-treated (vehicle control) cells (P < 0.01 to P < 0.001). At the molecular level, krill oil extract reduced the expression of EGFR, pEGFR (P < 0.001 for both) and their downstream signalling, pERK1/2 and pAKT (P < 0.01 to P < 0.001) without altering total ERK 1/2 and AKT levels. In addition, the expression of PD-L1 was reduced by 67 to 72% (P < 0.001) following the treatment with krill oil extract. CONCLUSION: This study has demonstrated that krill oil may be a potential therapeutic/adjunctive agent for CRC attributed to its anti-migratory effects.. The potential anti-cancer properties of krill oil are likely to be associated with the downregulation of EGFR, pEGFR and their downstream pERK/ERK1/2 and pAKT/AKT signalling pathways along with the downregulation of PD-L1. BioMed Central 2020-12-07 /pmc/articles/PMC7720407/ /pubmed/33287803 http://dx.doi.org/10.1186/s12906-020-03160-7 Text en © The Author(s) 2020 Open AccessThis 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Jayathilake, Abilasha G.
Veale, Margaret F.
Luwor, Rodney Brain
Nurgali, Kulmira
Su, Xiao Q.
Krill oil extract inhibits the migration of human colorectal cancer cells and down-regulates EGFR signalling and PD-L1 expression
title Krill oil extract inhibits the migration of human colorectal cancer cells and down-regulates EGFR signalling and PD-L1 expression
title_full Krill oil extract inhibits the migration of human colorectal cancer cells and down-regulates EGFR signalling and PD-L1 expression
title_fullStr Krill oil extract inhibits the migration of human colorectal cancer cells and down-regulates EGFR signalling and PD-L1 expression
title_full_unstemmed Krill oil extract inhibits the migration of human colorectal cancer cells and down-regulates EGFR signalling and PD-L1 expression
title_short Krill oil extract inhibits the migration of human colorectal cancer cells and down-regulates EGFR signalling and PD-L1 expression
title_sort krill oil extract inhibits the migration of human colorectal cancer cells and down-regulates egfr signalling and pd-l1 expression
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720407/
https://www.ncbi.nlm.nih.gov/pubmed/33287803
http://dx.doi.org/10.1186/s12906-020-03160-7
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