Imperial College London
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DrGeorgiosNteliopoulos

Faculty of Medicine, Department of Surgery & Cancer

Research Associate Biomarker
 
 
 
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Contact

 

georgios.nteliopoulos04

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Nikolakopoulou:2013:carcin/bgt257,
author = {Nikolakopoulou, Z and Nteliopoulos, G and Michael-Titus, AT and Parkinson, EK},
doi = {carcin/bgt257},
journal = {Carcinogenesis},
pages = {2716--2725},
title = {Omega-3 polyunsaturated fatty acids selectively inhibit growth in neoplastic oral keratinocytes by differentially activating ERK1/2.},
url = {http://dx.doi.org/10.1093/carcin/bgt257},
volume = {34},
year = {2013}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs)-eicosapentaenoic acid (EPA) and its metabolite docosahexaenoic acid (DHA)-inhibit cancer formation in vivo, but their mechanism of action is unclear. Extracellular signal-regulated kinase 1/2 (ERK1/2) activation and inhibition have both been associated with the induction of tumour cell apoptosis by n-3 PUFAs. We show here that low doses of EPA, in particular, inhibited the growth of premalignant and malignant keratinocytes more than the growth of normal counterparts by a combination of cell cycle arrest and apoptosis. The growth inhibition of the oral squamous cell carcinoma (SCC) lines, but not normal keratinocytes, by both n-3 PUFAs was associated with epidermal growth factor receptor (EGFR) autophosphorylation, a sustained phosphorylation of ERK1/2 and its downstream target p90RSK but not with phosphorylation of the PI3 kinase target Akt. Inhibition of EGFR with either the EGFR kinase inhibitor AG1478 or an EGFR-blocking antibody inhibited ERK1/2 phosphorylation, and the blocking antibody partially antagonized growth inhibition by EPA but not by DHA. DHA generated more reactive oxygen species and activated more c-jun N-terminal kinase than EPA, potentially explaining its increased toxicity to normal keratinocytes. Our results show that, in part, EPA specifically inhibits SCC growth and development by creating a sustained signalling imbalance to amplify the EGFR/ERK/p90RSK pathway in neoplastic keratinocytes to a supraoptimal level, supporting the chemopreventive potential of EPA, whose toxicity to normal cells might be reduced further by blocking its metabolism to DHA. Furthermore, ERK1/2 phosphorylation may have potential as a biomarker of n-3 PUFA function in vivo.
AU  - Nikolakopoulou,Z
AU  - Nteliopoulos,G
AU  - Michael-Titus,AT
AU  - Parkinson,EK
DO  - carcin/bgt257
EP  - 2725
PY  - 2013///
SP  - 2716
TI  - Omega-3 polyunsaturated fatty acids selectively inhibit growth in neoplastic oral keratinocytes by differentially activating ERK1/2.
T2  - Carcinogenesis
UR  - http://dx.doi.org/10.1093/carcin/bgt257
UR  - https://www.ncbi.nlm.nih.gov/pubmed/23892603
VL  - 34
ER  -
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