Abstract
Mediterranean diet components, such as olive oil and ω-3 polyunsaturated fatty acids (ω-3 PUFAs), can arrest cell growth and promote cell apoptosis. Recently, olive oil has been demonstrated to modulate type-1 cannabinoid (CB1) receptor gene expression in both human colon cancer cells and rat colon. The aim of this study was to investigate a possible link between olive oil and ω-3 PUFAs effects and CB1 receptor expression in both intestinal and adipose tissue of ApcMin/+ mice. To confirm the role for the CB1 receptor as a negative modulator of cell proliferation in human colon cancer, CB1 receptor gene expression was also detected in tumor tissue and in surrounding normal mucosa of patients with colorectal cancer (CRC). Dietary ω-3 PUFAs significantly inhibited intestinal polyp growth in mice, correlating with CB1 receptor gene and protein expression induction. CB1 receptor gene up-regulation was also detected in adipose tissue, suggesting a close communication between cancer cells and the surrounding environment. Tissue CB1 receptor induction was associated with a concurrent inactivation of the Wnt/β-catenin pathway. Moreover, there was a significant reduction in CB1 receptor gene expression levels in cancer tissue compared to normal surrounding mucosa of patients with CRC, confirming that in cancer the “protective” action of the CB1 receptor is lost.
Highlights
The evidence for the health benefits of dietary ω-3 polyunsaturated fatty acids (ω-3 PUFAs) has been drawn from different epidemiologic and controlled intervention studies [1,2]
In accordance with our previous studies, the number and volume of polyps (Figure 1b,c, respectively) in mice treated with olive oil and ω-3 PUFAs were significantly decreased as compared to polyps detected in mice fed standard diet (p < 0.05, ANOVA and Dunnett’s multiple comparison test)
The anti-proliferative action of diets enriched with olive oil and ω-3 was correlated with an induction of Cannabinoid receptor-1 (CB1) gene receptor expression
Summary
The evidence for the health benefits of dietary ω-3 polyunsaturated fatty acids (ω-3 PUFAs) has been drawn from different epidemiologic and controlled intervention studies [1,2]. Cannabinoids receptor agonists have been demonstrated to have an antitumor action, mostly via Cannabinoid receptor-1 (CB1) activation. We previously demonstrated that anandamide (Met-F-AEA), an endogenous agonist for the CB1 receptor, inhibits the proliferation of colon cancer cell lines. This anti proliferation effect was related to a significant reduction of cells in the S phase of the cell cycle and to a decrease of the cell polyamines content [9]. We have demonstrated an estrogenic induction of the CB1 receptor at mRNA and protein level in human colon cancer cells, suggesting a possible role of the CB1 receptor and its ligands as cell proliferation mediators [10]
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