The traditional Mediterranean diet is thought to represent a healthy lifestyle; especially given the incidence of several cancers including colorectal cancer is lower in Mediterranean countries compared to Northern Europe. Olive oil, a central component of the Mediterranean diet, is believed to beneficially affect numerous biological processes. We used phenols extracted from virgin olive oil on a series of in vitro systems that model important stages of colon carcinogenesis. The effect the extract on DNA damage induced by hydrogen peroxide was measured in HT29 cells using single cell microgel-electrophoresis. A significant anti-genotoxic linear trend (p 5 0.011) was observed when HT29 cells were preincubated with olive oil phenols (0,5,10,25,50, 75, 100 lg/ml) for 24 hr, then challenged with hydrogen peroxide. The olive oil phenols (50, 100 lg/ml) significantly (p 5 0.004, p 5 0.002) improved barrier function of CACO2 cells after 48 hr as measured by transepithelial resistance. Significant inhibition of HT115 invasion (p < 0.01) was observed at olive oil phenols concentrations of 25, 50, 75, 100 lg/ml using the matrigel invasion assay. No effect was observed on HT115 viability over the concentration range 0, 25, 50 75, 100 lg/ml after 24 hr, although 75 and 100 lg/ml olive oil phenols significantly inhibited HT115 cell attachment (p 5 0.011, p 5 0.006). Olive oil phenols had no significant effect on metastasis-related gene expression in HT115 cells. We have demonstrated that phenols extracted from virgin olive oil are capable of inhibiting several stages in colon carcinogenesis in vitro. ' 2005 Wiley-Liss, Inc.

Studies in human, animal and cellular systems suggest that phenols from virgin olive oil are capable of inhibiting several stages in carcinogenesis, including metastasis. The invasion cascade comprises cell attachment to extracellular matrix components or basement membrane, degradation of basement membrane by proteolytic enzymes and migration of cells through the modified matrix. In the present study, we investigated the effect of phenolics extracted from virgin olive oil (OVP) and its main constituents: hydroxytyrosol (3,4-dihydroxyphenylethanol), tyrosol (p-hydroxyphenylethanol), pinoresinol and caffeic acid. The effects of these phenolics were tested on the invasion of HT115 human colon carcinoma cells in a Matrigel invasion assay. OVP and its compounds showed different dose-related anti-invasive effects. At 25 lg/ml OVP and equivalent doses of individual compounds, significant anti-invasive effects were seen in the range of 45-55% of control. Importantly, OVP, but not the isolated phenolics, significantly reduced total cell number in the Matrigel invasion assay. There were no significant effects shown on cell viability, indicating the reduction of cell number in the Matrigel invasion assay was not due to cytotoxicity. There were also no significant effects on cell attachment to plastic substrate, indicating the importance of extracellular matrix in modulating the anti-invasive effects of OVP. In conclusion, the results from this study indicate that phenols from virgin olive oil have the ability to inhibit invasion of colon cancer cells and the effects may be mediated at different levels of the invasion cascade. ' 2007 Wiley-Liss, Inc.Key words: olive oil phenolics; colorectal cancer; invasion; adhesion; extracellular matrix In 2002, world cancer statistics for new colorectal cancer (CRC) cases were estimated to be more than 1 million, with more than 500,000 mortality cases. 1 Surgical resection is an effective treatment for localized disease, achieving a 5-year survival rate of 90%, but other normal treatments for metastatic disease remain ineffective. 2 Mediterranean countries have lower rates of CRC than other Western countries. 3 This has been attributed to a number of factors, one of which is consumption of olive oil. 3,4 Recently, olive oil phenolics have been shown to exert anticancer effects in a number of studies (reviewed in Refs. 5 and 6). Our previous study demonstrated that olive oil phenolics have the ability to inhibit initiation, promotion and invasion events in in vitro models of carcinogenesis. 7 Metastasis can be considered as a cascade of interrelated sequential steps. Cells must be able to disseminate from the primary tumor, invade the surrounding tissue, enter the circulatory system, evade immune responses, arrest at and colonize a distant site. 8 A 3-step hypothesis has been proposed to describe invasion of tumor cells: attachment to basement membrane or extracellular matrices (ECM), protease activity that induces local degradation of the matrix, and migration of tumor cells through the...

One common effect of tumor promoters is increased tight junction (TJ) permeability. TJs are responsible for paracellular permeability and integrity of the barrier function. Occludin is one of the main proteins responsible for TJ structure. This study tested the effects of physiological levels of phenol, ammonia, primary bile acids (cholic acid, CA, and chenodeoxycholic acid, CDCA), and secondary bile acids (lithocholic acid, LCA, and deoxycholic acid, DCA) on paracellular permeability using a Caco-2 cell model. Paracellular permeability of Caco-2 monolayers was assessed by transepithelial electrical resistance (TER) and the apical to basolateral flux of [14C]-mannitol. Secondary, but not primary, bile acids increased permeability as reflected by significantly decreased TER and increased mannitol flux. Both phenol and ammonia also increased permeability. The primary bile acid CA significantly increased occludin expression (P < 0.05), whereas CDCA had no significant effect on occludin expression as compared to the negative control. The secondary bile acids DCA and LCA significantly increased occludin expression (P < 0.05), whereas phenol had no significant effect on the protein expression as compared to the negative control. This suggests that the increased permeability observed with LCA, DCA, phenol, and ammonia was not related to an effect on occludin expression. In conclusion, phenol, ammonia, and secondary bile acids were shown to increase paracellular permeability and reduce epithelial barrier function at doses typical of levels found in fecal samples. The results contribute to the evidence these gut microflora-generated products have tumor-promoting activity.

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Objective: Incorporation of fish oil into food products provides a means of increasing n–3 fatty acid intake, particularly in populations where fish consumption remains low. The aim of the present study was to evaluate the bioavailability of n–3 PUFA in microencapsulated fish-oil-enriched foods compared with an equal amount of n–3 PUFAs contained in fish oil capsules. Methods: Twenty-five healthy female volunteers were randomly assigned to one of two groups for the 4-week intervention: one group received 0.9 g of n–3 PUFA/day as fish oil capsule (capsule group), while the second group (food group) received an equal amount of n–3 PUFA/day from enriched foods. Baseline and post-intervention samples were analysed for platelet fatty acid composition. Results: There was no significant difference in the change in platelet arachidonic acid (AA), eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA) between the two groups following the intervention. Conclusions: The results indicate that n–3 PUFA from microencapsulated fish-oil-enriched foods are as bioavailable as n–3 PUFA in a capsule. Fortification of foods with microencapsulated fish oil, therefore, offers an effective way of increasing n–3 PUFA intakes and status in line with current dietary recommendations.