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Hydroxytosol reduces colon cancer

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.

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RESEARCH TITLE: Hydroxytyrosol, a product from olive oil, reduces colon cancer growth by enhancing epidermal growth factor receptor degradation

COUNTRIES: Italy

CONDUCTED BY: Department of Life Sciences, University of Siena, Siena, Italy; Istituto Toscano Tumori (ITT), Florence, Italy

PUBLISHED ON: Molecular Nutrition & Food Research

RESEACH:

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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 hydroxytyrosol significantly down-regulates EGFR expression in human colorectal adenocarcinoma cells HT-29, CaCo2 and WiDr, and in HT-29 xenografts. Hydroxytyrosol accelerates EGFR degradation by reducing its half-life. Specifically, hydroxytyrosol induces EGFR ubiquitination which is mediated by phosphorylation at pY1045, the docking site for Cbl, thereby enabling receptor ubiquitination and degradation.

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Pretreatment with either the lysosomal inhibitor chloroquine, or the proteasomal inhibitor MG132 blocks hydroxytyrosol -induced EGFR down-regulation. In colon cancer cells, EGFR down-regulation by hydroxytyrosol is associated with reduced cell proliferation. Tumour growth and EGFR expression levels are also decreased by hydroxytyrosol treatment in HT-29 xenograft.

Discussion

We conclude that hydroxytyrosol down-regulates EGFR expression via lysosomal and proteasomal degradation, activated by hydroxytyrosol -induced EGFR phosphorylation at pY1045 and increased Cbl activity. Cbl activation induces, in turn, EGFR ubiquitination. Our results reveal a new mechanism for hydroxytyrosol  anti-tumour effects that may be important for colon tumour prevention and treatment.

YEAR: 2015

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