Hydroxytyrosol inhibits the proliferation of human colon adenocarcinoma cells through inhibition of ERK1/2 and cyclin D1.
Extra virgin olive oil is rich in phenolic compounds which are believed to exert beneficial effects against many pathological processes, including the development of colon cancer. We show that one of the major polyphenolic constituents of extra virgin olive oil, hydroxytyrosol (HT), exerts strong antiproliferative effects against human colon adenocarcinoma cells via its ability to induce a cell cycle block in G2/M. These antiproliferative effects were preceded by a strong inhibition of extracellular signal-regulated kinase (ERK)1/2 phosphorylation and a downstream reduction of cyclin D1 expression, rather than by inhibition of p38 activity and cyclooxygenase-2 (COX-2) expression. These findings are of particular relevance due to the high colonic concentration of HT compared to the other olive oil polyphenols and may help explain the inverse link between colon cancer and olive oil consumption.
Corona
Giulia
G
Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Reading, UK.
Deiana
Monica
M
Incani
Alessandra
A
Vauzour
David
D
Dessì
Maria Assunta
MA
Spencer
Jeremy P E
JP
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019938:Cyclin D1 / Q000037:antagonists & inhibitors*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010766:Phosphorylation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; C530104:CCND1 protein, human; C005975:3,4-dihydroxyphenylethanol; D019938:Cyclin D1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D010626:Phenylethyl Alcohol