Hydroxytyrosol, a product from olive oil, reduces colon cancer growth by enhancing epidermal growth factor receptor degradation
Terzuoli E, Giachetti A, Ziche M, Donnini S
Molecular nutrition & food research · 59 citations
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Nonprofit
- Associazione Italiana sul Cancro
Based on 1 listed funder(s).
Publication
- Published
- 2015-11-18 · Mol Nutr Food Res · vol. 60 · issue 3 · pp. 519–529
- Publisher
- Wiley
- Cited
- 80 citations · more than 93% of similar papers · 3.6× the field average
- Impact
- Top 10% most cited in its field
- References
- 47 works
- Access
- Open access (repository copy) · OTHER-OA
- Research areas
- Edible Oils Quality and Analysis · Fatty Acid Research and Health · Coconut Research and Applications
- Keywords
- Downregulation and upregulation, Epidermal growth factor receptor, MG132, Hydroxytyrosol, Cancer research, Chemistry, Phosphorylation, EGFR inhibitors, Ubiquitin, Cell growth, Colorectal cancer, Receptor, Cell biology, Biology, Cancer, Internal medicine, Biochemistry, Medicine, Polyphenol
- MeSH
- caco-2 cells, ht29 cells, lysosomes, animals, humans, mice, nude, colonic neoplasms, phenylethyl alcohol, proteasome endopeptidase complex, tyrosine, antineoplastic agents, phytogenic, xenograft model antitumor assays, phosphorylation, female, erbb receptors, olive oil
4 authors
From IT
- Erika TerzuoliUniversity of Siena
- Antonio GiachettiUniversity of Siena
- Marina ZicheUniversity of Siena; Tumour Institute of Tuscany
- Sandra Donnini · correspondingUniversity of Siena; Tumour Institute of Tuscany
Abstract
Scope
We studied the effects and mechanism of 2-(3,4-dihydroxyphenil)ethanol (or hydroxytyrosol, HT), a polyphenol from extra virgin olive oil, investigating the regulation of epidermal growth factor receptor (EGFR) expression in colon tumour cells.
Methods and results
We demonstrate that HT significantly downregulates EGFR expression in human colorectal adenocarcinoma cells HT-29, CaCo2, and WiDr, and in HT-29 xenografts. HT accelerates EGFR degradation by reducing its half-life. Specifically, HT induces EGFR ubiquitination that is mediated by phosphorylation at pY1045, the docking site for Cbl, thereby enabling receptor ubiquitination and degradation. Pretreatment with either the lysosomal inhibitor chloroquine, or the proteasomal inhibitor MG132 blocks HT-induced EGFR downregulation. In colon cancer cells, EGFR downregulation by HT is associated with reduced cell proliferation. Tumour growth and EGFR expression levels are also decreased by HT treatment in HT-29 xenograft.
Conclusion
We conclude that HT downregulates EGFR expression via lysosomal and proteasomal degradation, activated by HT-induced EGFR phosphorylation at pY1045 and increased Cbl activity. Cbl activation induces, in turn, EGFR ubiquitination. Our results reveal a new mechanism for HT's antitumour effects that may be important for colon tumour prevention and treatment.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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