Inhibition of p38/CREB phosphorylation and COX-2 expression by olive oil polyphenols underlies their anti-proliferative effects.
We investigated the anti-proliferative effects of an olive oil polyphenolic extract on human colon adenocarcinoma cells. Analysis indicated that the extract contained hydroxytyrosol, tyrosol and the various secoiridoid derivatives, including oleuropein. This extract exerted a strong inhibitory effect on cancer cell proliferation, which was linked to the induction of a G2/M phase cell cycle block. Following treatment with the extract (50 microg/ml) the number of cells in the G2/M phase increased to 51.82+/-2.69% relative to control cells (15.1+/-2.5%). This G2/M block was mediated by the ability of olive oil polyphenols (50 microg/ml) to exert rapid inhibition of p38 (38.7+/-4.7%) and CREB (28.6+/-5.5%) phosphorylation which led to a downstream reduction in COX-2 expression (56.9+/-9.3%). Our data suggest that olive oil polyphenols may exert chemopreventative effects in the large intestine by interacting with signalling pathways responsible for colorectal cancer development.
Corona
Giulia
G
Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights Campus, Reading RG2 6AP, UK.
Deiana
Monica
M
Incani
Alessandra
A
Vauzour
David
D
Dessì
M Assunta
MA
Spencer
Jeremy P E
JP
D000970:Antineoplastic Agents / Q000494:pharmacology; D018938:Caco-2 Cells; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry; D006801:Humans; D020935:MAP Kinase Signaling System; D000069463:Olive Oil; D010636:Phenols / Q000737:chemistry; D010766:Phosphorylation; D010938:Plant Oils; D059808:Polyphenols; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000970:Antineoplastic Agents; D017362:Cyclic AMP Response Element-Binding Protein; D005419:Flavonoids; D000069463:Olive Oil; D010636:Phenols; D010938:Plant Oils; D059808:Polyphenols; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases