ABSTRACT

In the Mediterranean basin, the “Mediterranean diet” has been widely considered to be responsible for a healthy and relatively disease-free population. Epidemiological data show that this diet and way of life have signicant protective effects against different types of chronic diseases, including cancer and coronary heart disease. To a certain degree, these effects can be attributed to olive oil consumption, one of the major constituents of the Mediterranean diet. The benecial role of olive oil is mainly due to a combination of its high oleic acid content (peroxidation-resistant lipid) and its minor components like polar phenolic compounds. More than 40 phenols have been identied in olive oil and a large number have been isolated and used in in vitro and in vivo studies conducted in order to investigate their actions. The major polar phenolic compounds identied and quantied in olive oil, as already mentioned in previous chapters of the book, belong to four different classes: simple phenols (hydroxytyrosol, tyrosol); secoiridoids (oleuropein, the aglycon of ligstroside, and

7.1 Introduction ......................................................................................................................... 129 7.2 Olive Oil Phenols and Cancer ............................................................................................. 130

7.2.1 Epidemiological Studies ........................................................................................... 130 7.2.2 Animal Models ......................................................................................................... 131 7.2.3 In Vitro Studies ......................................................................................................... 131

7.3 Mode of Action of Olive Oil Constituents .......................................................................... 132 7.3.1 Modication of the Redox Status ............................................................................. 132 7.3.2 Interference with Basic Cell Functions .................................................................... 133

7.3.2.1 Cell Cycle and Apoptosis ........................................................................... 133 7.3.2.2 Angiogenesis .............................................................................................. 135 7.3.2.3 Invasion and Metastasis ............................................................................. 136 7.3.2.4 Action on Adhesion Molecules and Cytoskeleton ..................................... 137

7.3.3 Mechanism of Action ............................................................................................... 139 7.3.3.1 Interaction with Steroid and Growth Factor Receptor-Mediated

Functions .................................................................................................... 139 7.3.3.2 Interaction with Specic Protein Kinases and Oncogenes/

Oncoproteins .............................................................................................. 140 7.3.3.3 Inhibition of Enzymes Related to Tumor Promotion and Metastasis ........ 145 7.3.3.4 Direct Effect on Nucleic Acids and Nucleoproteins .................................. 150

7.4 Other Pentacyclic Triterpenes ............................................................................................. 151 7.5 Effects of Oleic Acid ........................................................................................................... 152 7.6 Conclusions ......................................................................................................................... 152

their respective decarboxylated dialdehyde derivatives); avonoids (apigenin, luteolin); and lignans [(+)-1-acetoxypinoresinol and pinoresinol]. A limited number of studies deal with cellular or molecular actions of olive oil lignans. However, it is known that pinoresinol can be converted to mammalian lignans, called enterolignans (enterodiol and enterolactone) (Heinonen et al., 2001), formed by the intestinal microora after the consumption of plant lignans (Milder et al., 2005).