| THE OMEGA-3 POLYUNSATURATED FATTY ACID EICOSAPENTAENOIC ACID INHIBITS MOUSE MC-26 COLORECTAL CANCER CELL LIVER METASTASIS VIA INHIBITION OF PROSTAGLANDIN E(2) -DEPENDENT CELL MOTILITY. | |
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MedLine Citation:
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PMID: 22300262 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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purpose: The omega (ω)-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA) has anti-neoplastic activity at early stages of colorectal carcinogenesis, relevant to chemoprevention of colorectal cancer (CRC). We tested the hypothesis that EPA also has anti-CRC activity at later stages of colorectal carcinogenesis, relevant to treatment of metastatic CRC, via modulation of E-type prostaglandin (PG) synthesis. Methods: A BALB/c mouse model, in which intra-splenic injection of syngeneic MC-26 mouse CRC cells leads to development of liver metastases, was used. Dietary EPA was administered in the free fatty acid (FFA) form for 2 weeks before and after ultrasound-guided intra-splenic injection of 1 x 10(6) MC-26 cells (n = 16 each group). Results: Treatment with 5% (w/w) EPA-FFA was associated with a reduced MC-26 mouse CRC cell liver tumour burden compared with control animals (median liver weight 1.62g versus 1.03g; P < 0.034). Administration of 5% EPA-FFA was also linked to a significant increase in tumour EPA incorporation and lower intra-tumoral PGE(2) levels (with concomitant increased production of PGE(3) ). Liver tumours from 5% EPA-FFA treated mice demonstrated decreased bromodeoxyuridine-positive CRC cell proliferation and reduced phosphorylated extracellular signal-related kinase 1/2 expression at the invasive edge of tumours. A concentration-dependent reduction in MC-26 CRC cell Transwell® migration following EPA-FFA treatment (50-200µM) in vitro was rescued by exogenous PGE(2) (10µM) and PGE(1) -alcohol (1µM). Conclusions: EPA-FFA inhibits MC-26 CRC cell liver metastasis. EPA incorporation is associated with a 'PGE(2) to PGE(3) switch' in liver tumours. Inhibition of PGE(2) -EP4 receptor-dependent CRC cell motility likely contributes to the anti-neoplastic activity of EPA. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society. |
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Authors:
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G Hawcroft; M Volpato; G Marston; N Ingram; S L Perry; A J Cockbain; A D Race; A Munarini; A Belluzzi; P M Loadman; P L Coletta; M A Hull |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-2 |
Journal Detail:
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Title: British journal of pharmacology Volume: - ISSN: 1476-5381 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society. |
Affiliation:
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Section of Molecular Gastroenterology, Leeds Institute of Molecular Medicine, Wellcome Trust Brenner Building, St James's University Hospital, Leeds LS9 7TF, United Kingdom, Yorkshire Experimental Cancer Medicine Centre, Institute of Cancer Therapeutics, University of Bradford, Bradford BD7 1DP, United Kingdom and Department of Gastroenterology, Sant'Orsola Malpighi Hospital, University of Bologna, Bologna 40138, Italy. |
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